tag:theconversation.com,2011:/global/topics/early-detection-1197/articlesEarly detection – The Conversation2022-10-31T12:35:50Ztag:theconversation.com,2011:article/1917282022-10-31T12:35:50Z2022-10-31T12:35:50ZA blood test that screens for multiple cancers at once promises to boost early detection<figure><img src="https://images.theconversation.com/files/492187/original/file-20221027-37112-cq8dx0.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2000%2C1500&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A number of multicancer early detection tests are currently in development.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/medical-testing-royalty-free-image/1339206392">EK Image/Science Photo Library via Getty Images</a></span></figcaption></figure><p>Detecting cancer early before it spreads throughout the body can be lifesaving. This is why doctors <a href="https://www.uspreventiveservicestaskforce.org/uspstf/recommendation-topics/uspstf-a-and-b-recommendations">recommend regular screening</a> for several common cancer types, using a variety of methods. Colonoscopies, for example, screen for colon cancer, while mammograms screen for breast cancer. </p>
<p>While important, getting all these tests done can be logistically challenging, expensive and sometimes uncomfortable for patients. But what if a single blood test could screen for most common cancer types all at once? </p>
<p>This is the promise of multicancer early detection tests, or MCEDs. This year, President Joe Biden identified developing MCED tests as a priority for the <a href="https://www.whitehouse.gov/briefing-room/statements-releases/2022/02/02/fact-sheet-president-biden-reignites-cancer-moonshot-to-end-cancer-as-we-know-it/">Cancer Moonshot</a>, a US$1.8 billion federal effort to reduce the cancer death rate and improve the quality of life of cancer survivors and those living with cancer.</p>
<p>As a laboratory medicine <a href="https://dlmp.uw.edu/faculty/pritchard">physician and researcher</a> who develops molecular tests for cancer, I believe MCED tests are likely to transform cancer screening in the near future, particularly if they receive strong federal support to enable rapid innovation.</p>
<h2>How MCED tests work</h2>
<p>All cells in the body, including tumor cells, <a href="https://doi.org/10.1080%2F15384047.2019.1598759">shed DNA into the bloodstream</a> when they die. MCED tests look for the trace amounts of tumor DNA in the bloodstream. This circulating “cell-free” DNA contains information about what type of tissue it came from and whether it is normal or cancerous. </p>
<p>Testing to look for circulating tumor DNA in the blood is not new. These <a href="https://my.clevelandclinic.org/health/diagnostics/23992-liquid-biopsy">liquid biopsies</a> – a fancy way of saying blood tests – are already widely used for patients with advanced-stage cancer. Doctors use these blood tests to look for mutations in the tumor DNA that help guide treatment. Because patients with late-stage cancer tend to have a large amount of tumor DNA circulating in the blood, it’s relatively easy to detect the presence of these genetic changes.</p>
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<iframe width="440" height="260" src="https://www.youtube.com/embed/Yb4S4hi0Muw?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Scientists are using strands of DNA that circulate in the blood as a way to detect early-stage cancer.</span></figcaption>
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<p>MCED tests are different from existing liquid biopsies because they are trying to detect early-stage cancer, when there aren’t that many tumor cells yet. Detecting these cancer cells can be challenging early on because noncancer cells also shed DNA into the bloodstream. Since most of the circulating DNA in the bloodstream comes from noncancer cells, detecting the presence of a few molecules of cancer DNA is like finding a needle in a haystack.</p>
<p>Making things even more difficult, blood cells shed abnormal DNA naturally with aging, and these strands can be confused for circulating cancer DNA. This phenomenon, known as <a href="https://doi.org/10.1001/jamaoncol.2020.5161">clonal hematopoiesis</a>, confounded early attempts at developing MCED tests, with too many false positive results.</p>
<p>Fortunately, newer tests are able to <a href="https://doi.org/10.1126/science.abb9601">avoid blood cell interference</a> by focusing on a type of “molecular barcode” embedded in the cancer DNA that identifies the tissue it came from. These barcodes are a result of <a href="https://doi.org/10.1016/j.annonc.2020.02.011">DNA methylation</a>, naturally existing modifications to the surface of DNA that vary for each type of tissue in the body. For example, lung tissue has a different DNA methylation pattern than breast tissue. Furthermore, cancer cells have abnormal DNA methylation patterns that correlate with cancer type. By cataloging different DNA methylation patterns, MCED tests can focus on the sections of DNA that distinguish between cancerous and normal tissue and pinpoint the cancer’s origin site.</p>
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<a href="https://images.theconversation.com/files/492154/original/file-20221027-41807-p9y3fa.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Diagram of DNA methylation, showing chromosome unspooling into chromatin and individual histones with methyl and acetyl groups" src="https://images.theconversation.com/files/492154/original/file-20221027-41807-p9y3fa.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/492154/original/file-20221027-41807-p9y3fa.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=404&fit=crop&dpr=1 600w, https://images.theconversation.com/files/492154/original/file-20221027-41807-p9y3fa.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=404&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/492154/original/file-20221027-41807-p9y3fa.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=404&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/492154/original/file-20221027-41807-p9y3fa.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=507&fit=crop&dpr=1 754w, https://images.theconversation.com/files/492154/original/file-20221027-41807-p9y3fa.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=507&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/492154/original/file-20221027-41807-p9y3fa.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=507&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">DNA contains molecular patterns that indicate where in the body it came from.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Figure_16_03_03.jpg">CNX OpenStax/Wikimedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
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<h2>Testing options</h2>
<p>There are currently several MCED tests in development and in clinical trials. <a href="https://doi.org/10.1200/JCO.2017.76.8671">No MCED test</a> is currently FDA-approved or recommended by medical societies.</p>
<p>In 2021, the biotech company GRAIL launched the first commercially available MCED test in the U.S. Its <a href="https://health.clevelandclinic.org/the-galleri-test/">Galleri test</a> claims to detect over 50 different types of cancers. At least two other U.S.-based companies, <a href="https://doi.org/10.1377/hlthaff.2021.01316">Exact Sciences and Freenome</a>, and one Chinese company, <a href="https://doi.org/10.1038/s41467-020-17316-z">Singlera Genomics</a>, have tests in development. Some of these tests use different cancer detection methods in addition to circulating tumor DNA, such as looking for cancer-associated proteins in blood.</p>
<p>MCED tests are not yet typically covered by insurance. GRAIL’s Galleri test is currently <a href="https://www.galleri.com/the-galleri-test/cost">priced at $949</a>, and the company offers a payment plan for people who have to pay out of pocket. Legislators have <a href="https://www.congress.gov/bill/117th-congress/senate-bill/1873">introduced a bill in Congress</a> to provide Medicare coverage for MCED tests that obtain FDA approval. It is unusual for Congress to consider legislation devoted to a single lab test, and this highlights both the scale of the medical market for MCED and concerns about disparities in access without coverage for these expensive tests.</p>
<h2>How should MCED tests be used?</h2>
<p>Figuring out how MCED tests should be implemented in the clinic will take many years. Researchers and clinicians are just beginning to address questions on who should be tested, at what age, and how past medical and family history should be taken into account. <a href="https://prevention.cancer.gov/major-programs/mcd/questions-and-answers-cancer">Setting guidelines</a> for how doctors will further evaluate positive MCED results is just as important.</p>
<p>There is also concern that MCED tests may result in overdiagnoses of <a href="https://www.verywellhealth.com/what-does-indolent-mean-2615124">low-risk, asymptomatic cancers</a> better left undetected. This happened with <a href="https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/prostate-cancer-screening">prostate cancer screening</a>. Previously, guidelines recommended that all men ages 55 to 69 regularly get blood tests to determine their levels of PSA, a protein produced by cancerous and noncancerous prostate tissue. But now the recommendation is more nuanced, with screening suggested on an individual basis that takes into account personal preferences.</p>
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<a href="https://images.theconversation.com/files/492186/original/file-20221027-19202-1tbimh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Medical professional drawing blood from patient" src="https://images.theconversation.com/files/492186/original/file-20221027-19202-1tbimh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/492186/original/file-20221027-19202-1tbimh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/492186/original/file-20221027-19202-1tbimh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/492186/original/file-20221027-19202-1tbimh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/492186/original/file-20221027-19202-1tbimh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=502&fit=crop&dpr=1 754w, https://images.theconversation.com/files/492186/original/file-20221027-19202-1tbimh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=502&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/492186/original/file-20221027-19202-1tbimh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=502&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Questions remain on how MCEDs will be implemented in the clinic.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/nurse-help-patient-to-stop-bleeding-while-donating-royalty-free-image/1290652548">Boy Anupong/Moment via Getty Images</a></span>
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<p>Another concern is that further testing to confirm positive MCED results will be costly and a burden to the medical system, particularly if a full-body scan is required. The out-of-pocket cost for an MRI, for example, can <a href="https://www.goodrx.com/health-topic/diagnostics/how-much-does-an-mri-cost">run up to thousands of dollars</a>. And patients who get a positive MCED result but are unable to confirm the presence of cancer after extensive imaging and other follow-up tests may develop lifelong anxiety about a potentially missed diagnosis and continue to take expensive tests in fruitless search for a tumor.</p>
<p>Despite these concerns, early clinical studies show promise. A <a href="https://doi.org/10.1126/science.abb9601">2020 study</a> of over 10,000 previously undiagnosed women found 26 of 134 women with a positive MCED test were confirmed to have cancer. A <a href="https://doi.org/10.1016/j.annonc.2021.05.806">2021 study sponsored by GRAIL</a> found that half of the over 2,800 patients with a known cancer diagnosis had a positive MCED test and only 0.5% of people confirmed to not have cancer had a false positive test. The test performed best for patients with more advanced cancers but did detect about 17% of the patients who had very-early-stage disease.</p>
<p>MCED tests may soon revolutionize the way clinicians approach cancer screening. The question is whether the health care system is ready for them.</p><img src="https://counter.theconversation.com/content/191728/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Colin Pritchard does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Multicancer early detection tests are among the priorities of the Biden administration’s Cancer Moonshot. The tests show promise, but questions remain about when and how to use them.Colin Pritchard, Professor of Laboratory Medicine and Pathology, School of Medicine, University of WashingtonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1886552022-09-06T05:01:54Z2022-09-06T05:01:54ZA window to the brain: the retina gives away signs of Alzheimer’s disease and could help with early detection<figure><img src="https://images.theconversation.com/files/482934/original/file-20220906-13-omytfy.jpg?ixlib=rb-1.1.0&rect=907%2C201%2C3926%2C3522&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption"></span> </figcaption></figure><p>The retina has long been poeticised as the window to the soul, but research now shows it could be a window to the brain and act as an early warning system for cognitive decline. </p>
<p>A <a href="https://jnnp.bmj.com/content/92/9/983">growing body of research</a> suggests the retina is thinner in people with Alzheimer’s disease, reflecting the cell loss that is a hallmark of the neurodegenerative disease. </p>
<p>We investigated a group of middle-aged people who are part of the <a href="https://dunedinstudy.otago.ac.nz/">Dunedin Study</a>, a comprehensive longitudinal project that has continued for five decades. We found people with thinner retinal nerve fibre layers (one of the cell layers in the retina) had <a href="https://jamanetwork.com/journals/jamaophthalmology/article-abstract/2788716">slower mental processing speed</a>. This is one of the first cognitive processes to decline in Alzheimer’s disease.</p>
<p>The people in our study were 45 years old, which is young for investigating age-related neurological diseases like Alzheimer’s. But treatments and interventions are most effective when administered during the earliest stages of Alzheimer’s and it is crucial to find ways of identifying people’s risk as early as possible. Easy risk identification will also help with clinical trials for Alzheimer’s disease treatments. </p>
<h2>Why the retina is a good biomarker for the brain</h2>
<figure class="align-right ">
<img alt="A graphic of the layers in a retina." src="https://images.theconversation.com/files/482849/original/file-20220905-14-2maaxg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/482849/original/file-20220905-14-2maaxg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=1097&fit=crop&dpr=1 600w, https://images.theconversation.com/files/482849/original/file-20220905-14-2maaxg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=1097&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/482849/original/file-20220905-14-2maaxg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=1097&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/482849/original/file-20220905-14-2maaxg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1379&fit=crop&dpr=1 754w, https://images.theconversation.com/files/482849/original/file-20220905-14-2maaxg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1379&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/482849/original/file-20220905-14-2maaxg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1379&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The retina at the back of the eye is made up of different layers. From the bottom up are blood vessels, separated from the retina by Bruch’s membrane (blue), pigment-detecting cones (light purple) and rods (orange). In blue at the top of the image are the ganglion cells and a layer of nerve fibers.</span>
<span class="attribution"><span class="source">BSIP/Education Images/Universal Images Group via Getty Images</span></span>
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<p>The retina (the back of your eye) is part of the central nervous system, and some of its cells <a href="https://www.nature.com/articles/nrneurol.2012.227">connect directly to the brain</a>. </p>
<p>Many of the processes that happen in the brain also occur in retinal ganglion cells, another layer of cells that make up the retina. This includes some of the abnormal processes common in Alzheimer’s disease, such as the abnormal deposition of amyloid beta protein and cell loss.</p>
<p>Retinal imaging has many advantages over other imaging technologies. It’s fast, with each scan taking only a few seconds, non-invasive, painless and relatively cheap. </p>
<p>It’s also already widely available. In Aotearoa, every hospital eye department has an optical coherence tomography (OCT) device for imaging the retina, and these devices are increasingly available in primary care clinics and retail optometrists. </p>
<figure class="align-center ">
<img alt="A person having a retinal scan taken by an optical coherence tomography device." src="https://images.theconversation.com/files/480728/original/file-20220824-13-ov158i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/480728/original/file-20220824-13-ov158i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=428&fit=crop&dpr=1 600w, https://images.theconversation.com/files/480728/original/file-20220824-13-ov158i.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=428&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/480728/original/file-20220824-13-ov158i.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=428&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/480728/original/file-20220824-13-ov158i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=538&fit=crop&dpr=1 754w, https://images.theconversation.com/files/480728/original/file-20220824-13-ov158i.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=538&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/480728/original/file-20220824-13-ov158i.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=538&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Hospitals and some primary care clinics have an optical coherence tomography device to scan the retina.</span>
<span class="attribution"><span class="license">Author provided</span></span>
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<p>Retinal imaging also lends itself to being interpreted by artificial intelligence applications. This means assessment of Alzheimer’s disease risk from the retina could be quick, easy and widely available. </p>
<p>For these reasons, researchers are beginning to investigate how early the retina starts to thin in Alzheimer’s disease. The disease has an insidious onset, with a gradual decline in cognitive processes such as memory, but the underlying pathology tends to be fairly far along by the time people notice the symptoms and seek medical treatment. </p>
<p>If we can detect retinal thinning before the symptoms become apparent, it could be possible to identify people who are in the earliest stages of Alzheimer’s disease. </p>
<h2>Retinal thinning and cognitive decline in middle age</h2>
<p>The people we studied are all part of the unique Dunedin Study, which tracked the development of a thousand babies born in Ōtepoti Dunedin between April 1972 and March 1973. </p>
<p>They’ve been assessed repeatedly every few years since, on a wide range of topics including mental health, risk-taking behaviours, respiratory and cardiovascular function, social support and dental health, among others. </p>
<p>They’ve also repeatedly undergone cognitive tests since they were children, each time using similar formats and standardised tests. This means we can compare their cognitive performance in middle age with their own results from childhood. </p>
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Read more:
<a href="https://theconversation.com/vaccine-resistance-has-its-roots-in-negative-childhood-experiences-a-major-study-finds-180114">Vaccine resistance has its roots in negative childhood experiences, a major study finds</a>
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<p>Most cognitive tests used in Alzheimer’s studies are blunt tools designed to detect large drops in cognition. But the detailed cognitive data we have allow us to detect even small cognitive changes. </p>
<p>Using statistical techniques, we used each person’s cognitive scores in childhood to predict what we’d expect their cognitive score to be at age 45, and measured how far away they were from what we’d predicted. </p>
<p>A number of study members’ scores were substantially lower than what we’d expect, indicating they were experiencing cognitive decline, even in middle age. </p>
<figure class="align-center ">
<img alt="Person having an eye test" src="https://images.theconversation.com/files/482848/original/file-20220905-12-3fc4ry.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/482848/original/file-20220905-12-3fc4ry.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/482848/original/file-20220905-12-3fc4ry.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/482848/original/file-20220905-12-3fc4ry.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/482848/original/file-20220905-12-3fc4ry.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/482848/original/file-20220905-12-3fc4ry.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/482848/original/file-20220905-12-3fc4ry.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Research suggests people with thinner retinas have older looking brains and other structural brain abnormalities.</span>
<span class="attribution"><span class="source">Getty Images</span></span>
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<h2>Why this matters</h2>
<p>While there are a number of potential causes of cognitive decline, papers from our research group are building up a picture of the factors associated with this outcome. We found people experiencing cognitive decline by 45 have <a href="https://pubmed.ncbi.nlm.nih.gov/31822815/">older looking brains</a> and more tiny bleeds and lesions, known as hyperintensities, in their <a href="https://academic.oup.com/braincomms/article/1/1/fcz041/5670525">white matter</a> (measured using MRI). </p>
<p>Our <a href="https://www.biorxiv.org/content/10.1101/2022.08.31.506114v1">research</a> found people with thinner retinas had older looking brains and other structural brain abnormalities. This suggests cognitive decline, detected in its earliest stages, is associated with cell loss in the brain and the retina. </p>
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<a href="https://theconversation.com/illuminating-the-brain-one-neuron-and-synapse-at-a-time-5-essential-reads-about-how-researchers-are-using-new-tools-to-map-its-structure-and-function-187607">Illuminating the brain one neuron and synapse at a time – 5 essential reads about how researchers are using new tools to map its structure and function</a>
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<p>To investigate this question even further, we are now focusing on measuring study members’ levels of a specific type of protein (phosphorylated tau <a href="https://link.springer.com/article/10.1007/s00401-020-02195-x">pTau181</a>) which is abundant in neurons and deposited in cells in several neurodegenerative diseases. This is thought to be one of the earliest indicators of Alzheimer’s disease, and it will help us to understand whether the changes we are observing are specific to Alzheimer’s disease and how early they can be detected. </p>
<p>Developing treatments for advanced stages of Alzheimer’s disease has been <a href="https://www.bmj.com/content/374/bmj.n1682.long">ineffective</a> so far, and it seems likely future pharmaceutical treatments will be most effective in the earliest stages of the disease. </p>
<p>Also, lifestyle-based interventions may help to <a href="https://pubmed.ncbi.nlm.nih.gov/32741806/">mitigate symptomatic cognitive decline</a>. This makes early identification of people who would benefit from these interventions extremely important.</p><img src="https://counter.theconversation.com/content/188655/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ashleigh Barrett-Young receives funding from the Neurological Foundation of New Zealand.</span></em></p>A thinning of the retina is associated with earlier ageing of the brain. Widely available retinal imaging could help detect cognitive decline in its earliest stages.Ashleigh Barrett-Young, Postdoctoral Fellow in Psychology, University of OtagoLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1814152022-04-25T12:13:44Z2022-04-25T12:13:44ZOvarian cancer is not a silent killer – recognizing its symptoms could help reduce misdiagnosis and late detection<figure><img src="https://images.theconversation.com/files/458950/original/file-20220420-23-c2b2re.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C3332%2C2209&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Ovarian cancer is more likely to be cured with early diagnosis.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/pelvic-pain-stomachache-concept-hands-of-young-royalty-free-image/1128669705">Pornpak Khunatorn/iStock via Getty Images Plus</a></span></figcaption></figure><p>Ovarian cancer is the <a href="https://www.cdc.gov/cancer/ovarian/statistics/index.htm">most deadly</a> of gynecologic tumors. Fewer than 40% of those diagnosed with ovarian cancer are cured, and approximately <a href="https://www.cancer.org/cancer/ovarian-cancer/about/key-statistics.html">12,810 people</a> in the U.S. die from the disease every year. </p>
<p>For the past 25 years, scientists have tried to identify a screening test to detect ovarian cancer in its earliest stages, when the <a href="https://www.cancer.org/cancer/ovarian-cancer/detection-diagnosis-staging/survival-rates.html">chance of cure is high</a>. Unfortunately, multiple <a href="https://prevention.cancer.gov/major-programs/prostate-lung-colorectal-and-ovarian-cancer-screening-trial">clinical</a> <a href="https://doi.org/10.1016/S0140-6736(15)01224-6">trials</a> with hundreds of thousands of participants have failed to identify an effective way to screen for ovarian cancer. In fact, the U.S. Preventive Services Task Force gave ovarian cancer screening a <a href="https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/ovarian-cancer-screening">grade of D</a> in 2018, meaning it recommends against periodic screening because it doesn’t improve survival and can prove harmful to patients.</p>
<p>Because no effective screening test currently exists, <a href="https://dx.doi.org/10.3238%2Farztebl.2011.0635">70% of people with ovarian cancer</a> are diagnosed at advanced stages, when <a href="https://www.medscape.com/answers/255771-194612/what-is-the-prognosis-of-ovarian-cancer">chances of cure</a> are poor. Around 60% to 90% of people with stage one or two cancer that stays around the ovaries and pelvis are disease-free five years after diagnosis, compared with only 10% to 40% of those with stage three or four cancer that has spread through the abdomen and beyond. </p>
<p>But even those with advanced disease have a <a href="https://doi.org/10.1038/nrclinonc.2015.224">higher chance</a> of being cured if complete surgical removal is still possible. This makes early diagnosis all the more important for overall survival.</p>
<p>Without screening tests, many physicians wrongly assume that early diagnosis for ovarian cancer isn’t possible. As a <a href="https://scholar.google.com/citations?user=pn7haLoAAAAJ&hl=en">gynecologic oncologist</a> who treats hundreds of ovarian cancer patients each year, I was frustrated by these late diagnoses, and wondered if better recognition of its symptoms could help clinicians and patients identify ovarian cancer earlier.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/L_GYn7a8oBE?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Ovarian cancer is often misdiagnosed.</span></figcaption>
</figure>
<h2>Detectable symptoms</h2>
<p>Ovarian cancer has historically been called a “<a href="https://dx.doi.org/10.1017%2Fs0025727300000521">silent killer</a>,” because clinicians thought its symptoms were undetectable. Patients were often diagnosed so late that doctors thought nothing could be done.</p>
<p>But there have been many studies over the past 20 years demonstrating that ovarian cancer does have <a href="https://doi.org/10.1097/AOG.0000000000004664">early warning signs</a>. My colleagues and I conducted one of the <a href="https://doi.org/10.1002/1097-0142(20001115)89:10%3C2068::AID-CNCR6%3E3.0.CO;2-Z">earliest studies</a> in 2000. Our survey of 1,700 people with ovarian cancer found that 95% of patients reported noticeable symptoms three to 12 months before diagnosis. The most common symptoms were pain in their pelvis and abdomen, increased frequency and urge to urinate, difficulty eating or feeling full quickly, and bloating or abdominal distension. </p>
<p>Importantly, people with both advanced- and early-stage disease reported similar types of symptoms. <a href="https://doi.org/10.1016/j.ogc.2012.02.007">Subsequent studies</a> from multiple researchers further confirm that patients with even early-stage ovarian cancer experience frequent symptoms.</p>
<p>We also found that providers often misdiagnosed ovarian cancer as another condition. When we asked patients what their doctors told them was the cause of their symptoms, 15% had their symptoms attributed to irritable bowel disease, 12% to stress, 9% to gastritis, 6% to constipation, 6% to depression and 4% to some other cause. Thirty percent were given treatment for a different condition. And 13% were told there was nothing wrong.</p>
<p>One major issue has been distinguishing ovarian cancer symptoms from those of common gastrointestinal and urinary conditions. In <a href="https://doi.org/10.1002/cncr.22371">another study</a>, my team and I found that patients with ovarian cancer have symptoms with a recent onset and occur more than 50% of the month.</p>
<p>To facilitate early detection of ovarian cancer, my team and I compared the symptoms ovarian cancer patients experienced with those of patients without ovarian cancer. We <a href="https://doi.org/10.1002/cncr.22371">developed an index</a> that identified six important symptoms of ovarian cancer: bloating, increased abdominal size, feeling full quickly, difficulty eating, pelvic pain and abdominal pain. Symptoms needed to occur more than 12 times a month but to have lasted for less than a year. </p>
<p>Based on these criteria, our index was able to detect ovarian cancer in 60% to 85% of the patients in our study, a range similar to that achieved through diagnostic blood tests for ovarian cancer.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/458982/original/file-20220420-24670-fds9t5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Person talking to doctor in exam room" src="https://images.theconversation.com/files/458982/original/file-20220420-24670-fds9t5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/458982/original/file-20220420-24670-fds9t5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=377&fit=crop&dpr=1 600w, https://images.theconversation.com/files/458982/original/file-20220420-24670-fds9t5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=377&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/458982/original/file-20220420-24670-fds9t5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=377&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/458982/original/file-20220420-24670-fds9t5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=473&fit=crop&dpr=1 754w, https://images.theconversation.com/files/458982/original/file-20220420-24670-fds9t5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=473&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/458982/original/file-20220420-24670-fds9t5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=473&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Recognizing the symptoms of ovarian cancer could lead to earlier diagnosis.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/woman-at-a-check-up-royalty-free-image/1368068504">FatCamera/E+ via Getty Images</a></span>
</figcaption>
</figure>
<h2>Preventing ovarian cancer</h2>
<p>While early detection is important, there are also prevention strategies that can help reduce the risk of developing ovarian cancer.</p>
<p>If you have a family history of ovarian cancer, inform your doctor, who may recommend <a href="https://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet">genetic testing</a> to fully determine your risk, or prophylactic surgery to prevent the development of cancer.</p>
<p>Oral contraceptives, tubal ligation (or surgery to close the fallopian tubes), pregnancy and breastfeeding all <a href="https://www.cancer.gov/types/ovarian/patient/ovarian-prevention-pdq">reduce the risk</a> of ovarian cancer. </p>
<p>Finally, <a href="https://doi.org/10.1001/jamanetworkopen.2021.47343">up to 70%</a> of ovarian cancers may arise from the fallopian tubes. Removing the fallopian tubes at the time of another surgery may be another option to help reduce the risk of ovarian cancer. This should be done only if you do not plan on becoming pregnant in the future.</p>
<p>[<em>Get fascinating science, health and technology news.</em> <a href="https://memberservices.theconversation.com/newsletters/?nl=science&source=inline-science-fascinating">Sign up for The Conversation’s weekly science newsletter</a>.]</p><img src="https://counter.theconversation.com/content/181415/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Barbara Goff receives funding from National Institutes of Health, TEAL foundation. Ovarian Cancer Research Foundation and Marsha Rivkin Foundation</span></em></p>There are currently no effective tests to screen for ovarian cancer. But that doesn’t mean there aren’t ways to recognize and prevent it.Barbara Goff, Professor of Obstetrics and Gynecology, University of WashingtonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1564642021-03-09T13:35:58Z2021-03-09T13:35:58Z3 medical innovations fueled by COVID-19 that will outlast the pandemic<figure><img src="https://images.theconversation.com/files/388126/original/file-20210305-19-1xbafnd.jpg?ixlib=rb-1.1.0&rect=1233%2C95%2C5784%2C5892&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Gene-based vaccines had never been approved for humans before the coronavirus pandemic.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/covid-19-rna-vaccine-illustration-royalty-free-illustration/1296294288?adppopup=true">Juan Gaertner/Science Photo Library via Getty Images</a></span></figcaption></figure><p><em>A number of technologies and tools got a chance to prove themselves for the first time in the context of COVID-19. Three researchers working in gene-based vaccines, wearable diagnostics and drug discovery explain how their work rose to the challenge of the pandemic, and their hopes that each technology is now poised to continue making big changes in medicine.</em></p>
<p></p><hr><p></p>
<h2>Genetic vaccines</h2>
<p><strong>Deborah Fuller, Professor of Microbiology, University of Washington</strong></p>
<p>Thirty years ago, researchers for the first time injected mice with genes from a foreign pathogen to <a href="https://doi.org/10.1038/356152a0">produce an immune response</a>. Like many new discoveries, these first gene-based vaccines had their ups and downs. Early mRNA vaccines were hard to store and <a href="https://doi.org/10.1038/nrd.2017.243">didn’t produce the right type of immunity</a>. DNA vaccines were more stable but weren’t efficient at getting into the cell’s nucleus, so they <a href="https://dx.doi.org/10.1038%2Fnrg2432">failed to produce sufficient immunity</a>.</p>
<p>Researchers slowly overcame the problems of <a href="https://doi.org/10.1038/mt.2008.200">stability</a>, getting the genetic instructions <a href="https://doi.org/10.1073/pnas.1209367109">where they needed to be</a> and making them induce <a href="https://doi.org/10.1038/nrd.2017.243">more effective immune responses</a>. By 2019, academic labs and biotechnology companies all over the world had dozens of promising mRNA and DNA vaccines for infectious diseases, as well as for cancer in development or in <a href="https://dx.doi.org/10.3390%2Fvaccines7020037">phase 1 and phase 2 human clinical trials</a>.</p>
<p>When COVID-19 struck, mRNA vaccines in particular were ready to be put to a real-world test. The <a href="https://theconversation.com/how-mrna-vaccines-from-pfizer-and-moderna-work-why-theyre-a-breakthrough-and-why-they-need-to-be-kept-so-cold-150238">94% efficacy of the mRNA vaccines</a> surpassed health officials’ highest expectations.</p>
<p>DNA and mRNA vaccines offer huge advantages over traditional types of vaccines, since they use only genetic code from a pathogen – rather than the entire virus or bacteria. Traditional vaccines take months, if not years, to develop. In contrast, once scientists get the genetic sequence of a new pathogen, they can <a href="https://doi.org/10.3389/fimmu.2020.583077">design a DNA or mRNA vaccine in days</a>, identify a lead candidate for clinical trials within weeks and have <a href="https://doi.org/10.1038/s41541-020-0159-8">millions of doses manufactured within months</a>. This is basically what happened with the coronavirus.</p>
<p>Gene-based vaccines also produce precise and effective immune responses. They stimulate not only antibodies that block an infection, but also a strong T cell response that can <a href="https://www.gavi.org/vaccineswork/what-are-nucleic-acid-vaccines-and-how-could-they-be-used-against-covid-19#:%7E:text=Nucleic%20acid%20vaccines%20use%20genetic,immune%20response%20against%20it">clear an infection if one occurs</a>. This makes these vaccines better able to respond to mutations, and it also means they could be capable of <a href="https://www.genengnews.com/insights/immunotherapy-targets-emerging-infectious-diseases/">eliminating chronic infections</a> or <a href="https://doi.org/10.1038/d41586-019-03072-8">cancerous cells</a>.</p>
<p>The hopes that gene-based vaccines could one day provide a vaccine for malaria or HIV, cure cancer, replace less effective traditional vaccines or be ready to stop the next pandemic before it gets started are no longer far-fetched. Indeed, many <a href="https://doi.org/10.1016/j.coi.2020.01.006">DNA</a> and <a href="https://doi.org/10.1038/nrd.2017.243">mRNA</a> vaccines against a wide range of infectious diseases, for treatment of chronic infections and for cancer are already in advanced stages and clinical trials. As someone who has been working on these vaccines for decades, I believe their proven effectiveness against COVID-19 will usher in a new era of vaccinology with <a href="https://doi.org/10.1016/j.ymthe.2020.06.017">genetic vaccines at the forefront</a>.</p>
<p></p><hr><p></p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/388127/original/file-20210305-23-1yr4ab5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A person wearing a smart watch." src="https://images.theconversation.com/files/388127/original/file-20210305-23-1yr4ab5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/388127/original/file-20210305-23-1yr4ab5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/388127/original/file-20210305-23-1yr4ab5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/388127/original/file-20210305-23-1yr4ab5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/388127/original/file-20210305-23-1yr4ab5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/388127/original/file-20210305-23-1yr4ab5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/388127/original/file-20210305-23-1yr4ab5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Smartwatches and other wearable technologies allow users to capture more continuous health data than ever before.</span>
<span class="attribution"><a class="source" href="https://pixabay.com/photos/smartwatch-gadget-technology-smart-828786/">Pixabay</a></span>
</figcaption>
</figure>
<h2>Wearable tech and early illness detection</h2>
<p><strong>Albert H. Titus, Professor of Biomedical Engineering, University at Buffalo</strong></p>
<p>During the pandemic, researchers have taken full advantage of the proliferation of smartwatches, smart rings and other wearable health and wellness technology. These devices can measure a person’s <a href="https://doi.org/10.1038/s41598-020-78355-6">temperature</a>, <a href="https://dx.doi.org/10.2196%2F10828">heart rate</a>, <a href="https://dx.doi.org/10.2196%2Fjmir.9157">level of activity</a> and other <a href="https://dx.doi.org/10.2196%2F16811">biometrics</a>. With this information, researchers have been able to track and <a href="https://doi.org/10.2196/26107">detect COVID-19 infections</a> even before people notice they have any symptoms.</p>
<p>As wearable usage and adoption <a href="https://www.gartner.com/en/newsroom/press-releases/2021-01-11-gartner-forecasts-global-spending-on-wearable-devices-to-total-81-5-billion-in-2021">grew in recent years</a>, researchers began studying the ability of these devices to <a href="https://dx.doi.org/10.3390%2Fnano9060813">monitor disease</a>. However, although real-time data collection was possible, previous work had focused primarily on chronic diseases.</p>
<p>But the pandemic both served as a lens to focus many researchers in the field of health wearables and offered them an unprecedented opportunity to study real-time <a href="https://doi.org/10.1038/s41928-020-00533-1">infectious disease detection</a>. The number of people potentially affected by a single disease – COVID-19 – at one time gave researchers a large population to draw from and to test hypotheses on. Combined with the fact that <a href="https://www.gartner.com/en/newsroom/press-releases/2021-01-11-gartner-forecasts-global-spending-on-wearable-devices-to-total-81-5-billion-in-2021">more people than ever</a> are using wearables with health monitoring functions and that these devices collect lots of useful data, researchers were able to try to diagnose a disease solely using data from wearables – an experiment they could only dream of before.</p>
<p>Wearables can detect symptoms of COVID-19 or other illnesses <a href="https://doi.org/10.1038/s41551-020-00640-6">before symptoms are noticeable</a>. While they have proved to be capable of detecting sickness early, the symptoms wearables detect are <a href="https://doi.org/10.1038/s41928-020-00533-1">not unique to COVID-19</a>. These symptoms can be predictive of a number of potential illnesses or other health changes, and it is much harder to say what illness a person has versus simply saying they are <a href="https://doi.org/10.1016/j.jiph.2011.05.002">sick with something</a>. </p>
<p>Moving into the post-pandemic world, it’s likely that more people will <a href="https://www.gartner.com/en/newsroom/press-releases/2021-01-11-gartner-forecasts-global-spending-on-wearable-devices-to-total-81-5-billion-in-2021">incorporate wearables</a> into their lives and that the devices will only improve. I expect the knowledge researchers have gained during the pandemic on how to use wearables to monitor health will form a starting point for how to handle future outbreaks – not just of viral pandemics, but potentially of other events such as food poisoning outbreaks and seasonal flu episodes. But since wearable tech is concentrated within pockets of affluent and <a href="https://dx.doi.org/10.1016%2Fj.ijinfomgt.2020.102209">younger populations</a>, the research community and society as a whole must simultaneously address the disparities that exist.</p>
<p></p><hr><p></p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/388128/original/file-20210305-23-cskouk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A map showing proteins connections." src="https://images.theconversation.com/files/388128/original/file-20210305-23-cskouk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/388128/original/file-20210305-23-cskouk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=590&fit=crop&dpr=1 600w, https://images.theconversation.com/files/388128/original/file-20210305-23-cskouk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=590&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/388128/original/file-20210305-23-cskouk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=590&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/388128/original/file-20210305-23-cskouk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=742&fit=crop&dpr=1 754w, https://images.theconversation.com/files/388128/original/file-20210305-23-cskouk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=742&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/388128/original/file-20210305-23-cskouk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=742&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Every place that a coronavirus protein interacts with a human protein is a potential druggable site.</span>
<span class="attribution"><a class="source" href="http://qbi.ucsf.edu/COVID-19">QBI Coronavirus Research Group</a>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<h2>A new way to discover drugs</h2>
<p><strong>Nevan Krogan, Professor of Cellular Molecular Pharmacology and Director of the Quantitative Biosciences Institute, University of California, San Francisco</strong></p>
<p>Proteins are the molecular machines that make your cells function. When proteins malfunction or are hijacked by a pathogen, you often get disease. Most drugs work by disrupting the action of one or several of these <a href="https://www.cancer.gov/about-cancer/treatment/types/targeted-therapies/targeted-therapies-fact-sheet">malfunctioning or hijacked proteins</a>. So a logical way to look for new drugs to treat a specific disease is to study individual genes and proteins that are directly affected by that disease. For example, researchers know that the BRCA gene – a gene that protects your DNA from being damaged – is closely related to the development of breast and ovarian cancer. So a lot of work has focused on finding drugs that affect the <a href="https://doi.org/10.1038/s41571-018-0055-6">function of the BRCA protein</a>.</p>
<p>However, single proteins working in isolation are usually not solely responsible for disease. Genes and the proteins they encode are part of complicated networks – the BRCA protein <a href="https://doi.org/10.1073/pnas.0805242105">interacts with tens to hundreds</a> of other proteins that help it perform its cellular functions. My colleagues and I are part of a <a href="https://doi.org/10.1016/j.molcel.2018.07.010">small but growing</a> field of <a href="https://doi.org/10.1016/j.cell.2018.08.044">researchers</a> who study these <a href="https://doi.org/10.1038/nature04670">connections and interactions among proteins</a> – what we call protein networks. </p>
<p>For a few years now, my colleagues and I have been exploring the potential of these networks to find more ways drugs could ameliorate disease. When the coronavirus pandemic hit, we knew we had to try this approach and see if it could be used to rapidly find a treatment for this emerging threat. We immediately started <a href="https://theconversation.com/covid-19-treatment-might-already-exist-in-old-drugs-were-using-pieces-of-the-coronavirus-itself-to-find-them-133701">mapping the extensive network of human proteins</a> that SARS-CoV-2 hijacks so it can replicate.</p>
<p>Once we built this map, we pinpointed human proteins in the network that <a href="https://theconversation.com/covid-19-treatment-might-already-exist-in-old-drugs-were-using-pieces-of-the-coronavirus-itself-to-find-them-133701">drugs could easily target</a>. We found <a href="https://doi.org/10.1038/s41586-020-2286-9">69 compounds</a> that influence the proteins in the coronavirus network. 29 of them are already FDA-approved treatments for other illnesses. On Jan. 25 we published a paper showing that one of the drugs, Aplidin (Plitidepsin), currently being used to treat cancer, is <a href="https://doi.org/10.1126/science.abf4058">27.5 times more potent than remdesivir</a> in treating COVID-19, <a href="https://doi.org/10.1101/2021.01.24.427991">including one of the new variants</a> The drug has been approved for phase 3 clinical trials in 12 countries as a <a href="https://clinicaltrials.gov/ct2/show/NCT04784559">treatment for the new coronavirus</a>.</p>
<p>But this idea of mapping the protein interactions of diseases to look for novel drug targets doesn’t apply just to the coronavirus. We have now used this approach on <a href="http://hpmi.ucsf.edu">other pathogens</a> as well as other diseases including <a href="http://ccmi.org">cancer</a>, neurodegenerative and <a href="http://pcmi.ucsf.edu">psychiatric disorders</a>.</p>
<p>These maps are allowing us to connect the dots among many seemingly disparate aspects of single diseases and discover new ways drugs could treat them. We hope this approach will allow us and researchers in other areas of medicine to discover new therapeutic strategies and also see whether any old drugs might be repurposed to treat other conditions.</p>
<p>[<em>Understand new developments in science, health and technology, each week.</em> <a href="https://theconversation.com/us/newsletters/science-editors-picks-71/?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=science-understand">Subscribe to The Conversation’s science newsletter</a>.]</p><img src="https://counter.theconversation.com/content/156464/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Deborah Fuller is a co-founder of Orlance, Inc that is developing a needle-free technology for delivery of DNA and RNA vaccines. She has grant funding from the National Institutes of Health, the Department of Defense and the Washington Research Foundation.</span></em></p><p class="fine-print"><em><span>Albert H. Titus has received research funding from the National Science Foundation, the National Institutes of Health, and the Department of Defense. He has also received funding for research in this area from Garwood Medical Devices. He is a Fellow of the National Academy of Inventors, a Senior Member of the IEEE, a member of BMES, ASEE, and is a member of the BME Council of Chairs. </span></em></p><p class="fine-print"><em><span>Nevan Krogan receives funding from NIH, DARPA and Roche Pharmaceuticals.</span></em></p>The coronavirus pandemic has driven a lot of scientific progress in the past year. But just as some of the social changes are likely here to stay, so are some medical innovations.Deborah Fuller, Professor of Microbiology, School of Medicine, University of WashingtonAlbert H. Titus, Professor of Biomedical Engineering, University at BuffaloNevan Krogan, Professor and Director of Quantitative Biosciences Institute & Senior Investigator at the Gladstone Institutes, University of California, San FranciscoLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1222492019-08-23T12:20:46Z2019-08-23T12:20:46ZNew blood screening may detect ovarian cancer two years before other methods<figure><img src="https://images.theconversation.com/files/289071/original/file-20190822-170956-zstdsq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/real-female-hairless-fight-against-cancer-243554755?src=QqPUzHwuo1ierIyyU9MAMQ-1-2">fototip/Shutterstock</a></span></figcaption></figure><p>Ovarian cancer has a high mortality risk because it is so often diagnosed at <a href="https://onlinelibrary.wiley.com/doi/full/10.3322/caac.21456">a very late stage</a>. In a <a href="https://www.nature.com/articles/s41416-019-0544-0">new study</a>, our team has shown that detection rates can be significantly improved by screening for a specific set of proteins in the bloodstream. This could mean detection of ovarian cancer up to two years before current screenings allow.</p>
<p>Cancer tests walk a harsh line between missing cancer and misdiagnosing healthy people. If you make your test too strict, you will fail to detect traces of real cancers that are present. If it is too lenient you will falsely detect cancer where it doesn’t exist.</p>
<p>While it might seem obvious we should tip the scales in favour of catching every cancer, the burden this places on the health system <a href="https://theconversation.com/medical-researchers-raise-alarm-on-overdiagnosis-12471">can be unsustainable</a>. Not to mention the stress and potentially dangerous treatment it can mean for healthy people.</p>
<p>Our group is working to improve this balancing act in the diagnosis of ovarian cancer, the statistics for which speak for themselves. In 2016, 4,227 women <a href="https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/ovarian-cancer">died from ovarian cancer</a>. The overall five year survival for stage III & IV ovarian cancer (late stage) is only 22%, making this the <a href="https://www.ncbi.nlm.nih.gov/pubmed/22237781">most lethal</a> female reproductive cancer. When ovarian cancer is detected early, the patient’s prospects are much better, with approximately 90% of women diagnosed at stage I (early stage) <a href="https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/ovarian-cancer">surviving five years or more</a>.</p>
<h1>Red herrings in current cancer detection</h1>
<p>Unfortunately, ovarian cancers are often not caught early enough. Almost six in ten ovarian cancer cases are <a href="https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/ovarian-cancer">diagnosed at a late stage</a> in England and Northern Ireland today, resulting in a <a href="https://www.ncbi.nlm.nih.gov/pubmed/27903971">high death rate</a>.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/289072/original/file-20190822-170946-1kcsan7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/289072/original/file-20190822-170946-1kcsan7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/289072/original/file-20190822-170946-1kcsan7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/289072/original/file-20190822-170946-1kcsan7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/289072/original/file-20190822-170946-1kcsan7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/289072/original/file-20190822-170946-1kcsan7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/289072/original/file-20190822-170946-1kcsan7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="attribution"><a class="source" href="https://www.shutterstock.com/download/success?u=http%3A%2F%2Fdownload.shutterstock.com%2Fgatekeeper%2FW3siZSI6MTU2NjUwMzg4OCwiYyI6Il9waG90b19zZXNzaW9uX2lkIiwiZGMiOiJpZGxfMTM3NzQ1ODUwNCIsImsiOiJwaG90by8xMzc3NDU4NTA0L2h1Z2UuanBnIiwibSI6MSwiZCI6InNodXR0ZXJzdG9jay1tZWRpYSJ9LCJsUXhjL0dwbjhwZk5VZHNzb1dxYUNyN2NmUjAiXQ%2Fshutterstock_1377458504.jpg&ir=true&pi=33421636&m=1377458504&src=y6qv_ROL2M0fAm5GPdCpcQ-1-7">Iconic Bestiary/Shutterstock</a></span>
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<p>Late detection of ovarian cancers is mostly due to the “non-specific” nature of its symptoms. Currently most blood tests measure the levels of a <a href="https://en.wikipedia.org/wiki/CA-125">protein CA125</a>. But using this as a marker for cancer in the blood <a href="https://theconversation.com/why-single-blood-markers-for-disease-will-become-a-thing-of-the-past-41636">is not reliable</a> as it can also be elevated in pregnancy, during a woman’s period, and other non fatal conditions (such as <a href="https://www.nhs.uk/conditions/endometriosis/">endometriosis</a>). Additionally, not all cancer patients show this marker. Studies have shown it is <a href="https://www.ncbi.nlm.nih.gov/pubmed/2651469">only elevated in around 50%</a> of early stage cancers.</p>
<p>For this reason, our research team has been working with an international group of experts from the universities of New South Wales, Milan and Manchester, to develop a combination of proteins we can use to identify cancer earlier than is currently possible.</p>
<p><a href="https://www.ncbi.nlm.nih.gov/pubmed/28664912">Our previous work</a> lead to the identification of four <a href="https://www.ncbi.nlm.nih.gov/pubmed/26815306">possible markers</a> we could look for in the blood to maximise the power of our tests (protein CA125, phosphatidylcholine-sterol acyltransferase, vitamin K-dependent protein Z, and C-reactive protein).</p>
<h1>A time capsule of blood samples</h1>
<p>Armed with our panel of blood markers, the next stage was to test for effectiveness in a large group of women. Part of the success of our study came from the <a href="https://www.ncbi.nlm.nih.gov/pubmed/31388184">incredible dataset</a> we had access to thanks to the United Kingdom Collaborative Trial for Ovarian Cancer Screening (<a href="https://gtr.ukri.org/projects?ref=G0801228">UKCTOCS</a>). From the 200,000 women registered in this database, we were able to select 80 women (49 ovarian cancer cases, and 31 healthy people). Blood samples from these women had been taken every year for seven years before the ovarian cancer patients were diagnosed with the disease.</p>
<p>This provided us with a very powerful tool. With this time capsule of samples we were able to observe how levels of our four target proteins changed over time between patients and healthy individuals. In essence, it allowed us to see directly if the proteins differed between patients and the healthy people over time. Because the samples were taken over such a long period, we could track back over the seven years to see when the first time the proteins would allow us to detect the disease.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/289074/original/file-20190822-170922-ksv1jh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/289074/original/file-20190822-170922-ksv1jh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=262&fit=crop&dpr=1 600w, https://images.theconversation.com/files/289074/original/file-20190822-170922-ksv1jh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=262&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/289074/original/file-20190822-170922-ksv1jh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=262&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/289074/original/file-20190822-170922-ksv1jh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=329&fit=crop&dpr=1 754w, https://images.theconversation.com/files/289074/original/file-20190822-170922-ksv1jh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=329&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/289074/original/file-20190822-170922-ksv1jh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=329&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">shutterstock time.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-vector/pixel-flat-people-run-over-clocks-1427233007?src=rZUwIjIjoUMvNj22KHqosg-1-0">New Design Illustrations/ Shutterstock</a></span>
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<p>We then developed a computerised tool that assessed changes in protein levels to determine the “predicted risk” of ovarian cancer for each person (cancer patients and healthy people). The tool was asked to grade the risk of ovarian cancer for each person at each point along the seven year timeline (rating them severe, elevated, intermediate, or normal).</p>
<p>This initial work demonstrated that the screening tool has the potential to diagnose ovarian cancer one to two years earlier than current diagnosis. Our results also suggest it could identify 60% of the most aggressive ovarian cancers around one year before currently possible.</p>
<h1>The future - digital biological maps</h1>
<p>The results of this study are encouraging but this research is still at an early stage. We are now setting up a study to verify our results in a large group, which will provide us with around 1,000 blood samples. By using a technique called <a href="https://www.atascientific.com.au/spectrometry/">SWATH mass spectrometry</a>, we can create a digital map of all the proteins in a person’s system at that time.</p>
<p>This means we do not have to rely on physical blood samples, which can get used up or expire. If future research suggests a new protein is important, we can come back in the future to look at these samples again and can share them easily with other research groups. We hope this study will provide the data we need to advocate for an ovarian cancer screening programme.</p>
<p>By optimising these methods we also hope we can move towards a stage where ovarian cancer is diagnosed in stages I and II in most women, when treatment can really make a difference.</p><img src="https://counter.theconversation.com/content/122249/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>This research was funded by the CRUK and the eve appeal . </span></em></p><p class="fine-print"><em><span>Ciaren Graham receives funding unrelated to the current study</span></em></p>We need to change diagnosis of ovarian cancer from late stage to early - scientists make stepsBobby Graham, Reader in the School of Biological Sciences, Queen's University BelfastCiaren Graham, Senior Lecturer in the School of Biological Sciences, Queen's University BelfastLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/441662015-07-08T05:24:39Z2015-07-08T05:24:39ZNew lock-and-key technology promises rapid cancer testing for developing world<p>One of the biggest challenges in modern medicine is diagnosis. This is particularly important in cancer, where early detection can dramatically improve the chance of survival. </p>
<p>Diagnosis is difficult enough when you have access to fully-equipped laboratories and reliable technology. But what happens in developing countries where even basic infrastructure like refrigeration may not be available? </p>
<p>The answer is shockingly clear. On average, <a href="http://www.who.int/dg/speeches/2010/iaea_forum_20100921/en/">70% of people</a> in developing countries do not get diagnosed until a late stage, when treatment is no longer effective. As a result of this, there is a big international drive to develop simple and accurate diagnostic technology.</p>
<p>A lot of research in early cancer diagnosis has focused <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3078627/">on biomarkers</a>. These are molecules, cells or any other measurable biological characteristic that can be used as an objective way to detect disease. Biomarkers are particularly useful since they do not rely on symptoms perceived by the patient, which can be ambiguous or may not appear until the disease has progressed substantially. </p>
<h2>Glycoproteins</h2>
<p>For detecting cancer (and in fact many other diseases), a useful class of biomarkers are <a href="http://www.wisegeek.com/what-is-a-glycoprotein.htm">the glycoproteins</a>. These molecules are proteins that are bound to one or more carbohydrate chains (sugars). They are found throughout the body, in blood, mucus, saliva and even sperm and they can be a signal for disease. If a suitable detection device is developed, a simple sample, for example of blood or urine, could be all that is needed to detect a cancer in its early stages. </p>
<p>Crucially, the biological function of a glycoprotein depends on its chemical structure. What is more important for disease diagnosis is that the chemical structure of a glycoprotein can be changed by the disease. This makes them ideal as a target for accurately detecting specific diseases. </p>
<p>Despite this promise, there are currently two big problems with using glycoproteins to diagnose cancer. The first problem is the technology. Existing methods rely on antibodies to detect <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3404449/">glycoproteins</a>. Antibodies are large proteins produced by our immune systems. They can be generated for use in devices, but this is challenging. They generally also need to be stored in refrigerators and they are readily degraded by UV light. </p>
<p>The second problem with glycoproteins is accuracy. Current detection methods rely on the fact that many individuals with cancer produce higher levels of glycoproteins. They do not account for healthy people who may naturally have high levels of certain glycoproteins. Some cancer patients may also have anomalously low levels of glycoproteins. Detection of glycoprotein levels with antibodies can therefore lead to a large number of false positive and negative results. This is distressing for the patient and can also waste crucial resources if a healthy person is sent for further testing or unnecessary treatment.</p>
<p>If early cancer diagnosis is to become available across the world, we need new technologies that are easy to transport and store. There also need to be substantial advances in accuracy. </p>
<p>Researchers at the University of Birmingham <a href="http://pubs.rsc.org/en/Content/ArticleLanding/2015/SC/C5SC02031J#!divAbstract">have</a> come up with some clever chemistry that might solve both of these problems. The team has approached the problem from a different direction. Rather than just detecting levels of glycoproteins, they have created a method which can identify specific glycoproteins for specific diseases. They do this by detecting both the shape of the glycoprotein and its particular chemical fingerprint. </p>
<h2>Lock and key</h2>
<p>The method works by taking a disease biomarker (in this case, a glycoprotein associated with prostate cancer) and essentially taking a cast of it. The prostate cancer glycoprotein is tethered to a surface and detection molecules are assembled around it. When the glycoprotein is removed, it leaves behind a perfect chemical “cast”. The group have essentially made a lock and the only key that will fit is the specific prostate cancer glycoprotein. Other glycoproteins might be the right size, but they won’t be able to bind to the very specific molecules inside the lock.</p>
<p>This new work could pave the way to fast and accurate cancer diagnosis. What is particularly exciting is that the method does not rely on antibodies. This means that there is no need for special storage, which could make a big difference for early cancer diagnosis in the developing world. </p>
<p>Another exciting feature of this work is the scope for diagnosing other problems. The prostate cancer glycoprotein they have used is just a template. In theory, they should be able to make a device using any glycoprotein. This would mean the technology could be adapted according to what disease you want to detect, not just cancers, but also immune deficiencies, neurodegenerative diseases and cardiovascular disorders.</p><img src="https://counter.theconversation.com/content/44166/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Zoe Schnepp does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>A new way of matching cancer biomarkers in bodily fluids could lead to produce detection technology that doesn’t need expensive labs.Zoe Schnepp, Research Fellow in Chemistry, University of BirminghamLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/165842013-08-05T04:32:34Z2013-08-05T04:32:34ZTool to predict women’s cancer risk could prompt lifestyle changes<figure><img src="https://images.theconversation.com/files/28530/original/6dz84zc8-1375408197.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The predictive tool might help women make decisions about changing their lifestyle.</span> <span class="attribution"><span class="source">Image from shutterstock.com</span></span></figcaption></figure><p>Researchers in the United States have <a href="http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001492">developed a new model</a> to predict women’s risk of developing breast, uterine and ovarian cancer, based on individual lifestyle factors. These three cancers make up one-third of all invasive cancers diagnosed among Australian women, with <a href="http://www.aihw.gov.au/acim-books/">more than 17,000</a> diagnosed each year. </p>
<p>While the prognosis for women who are diagnosed with these cancers is improving, due in part to earlier detection and more effective treatment, <a href="http://www.aihw.gov.au/acim-books/">nearly 4,000 Australian women</a> died due to one of these cancers in 2007. Added to this is the impact a cancer diagnosis has on quality of life and psychological well-being.</p>
<p>The ideal way of reducing the impact of cancer is to prevent the development of cancer in the first place. An estimated <a href="http://cancerforum.org.au/Issues/2012/March/Forum/Impact_future_cancer_incidence.htm">one-third of cancers</a> can be prevented through improvements in lifestyle behaviours, such as not smoking, reducing alcohol intake, increasing physical activity and having a more nutritious diet. </p>
<p>So, how does the new tool work, and how accurate is it likely to be?</p>
<h2>Assessing risk</h2>
<p>The researchers used the results of a <a href="http://dietandhealth.cancer.gov/">large study of almost 200,000 healthy women aged over 50 </a> to develop mathematical models that tries to estimate a woman’s risk of each type of cancer. They then analysed a <a href="http://www.ncbi.nlm.nih.gov/pubmed/21642681">separate cohort</a> of 64,440 initially healthy women aged 55 to see how the model performed.</p>
<p>The model is based on the combination of known risk factors a woman has, including body mass index, smoking status and level of alcohol consumption. It also takes into account other factors such as: </p>
<ul>
<li>age at birth of first child </li>
<li>number of children </li>
<li>family history of breast of ovarian cancer </li>
<li>age at menopause</li>
<li>the use of oral contraceptives and hormone replacement therapy. </li>
</ul>
<p>The magnitude and direction of these associations depend on the specific cancer. </p>
<p>The idea behind these models was that having an estimate of future risk would help women and their doctors make more informed decisions about cancer screening, prophylactic surgery, improving preventive behaviours, and use of specific medicines.</p>
<p>Although there have been previous risk factor models for breast cancer, this is the first study that has examined models for breast cancer, endometrial cancer and ovarian cancer from the one cohort.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/28564/original/2n4t2pqy-1375427403.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/28564/original/2n4t2pqy-1375427403.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/28564/original/2n4t2pqy-1375427403.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/28564/original/2n4t2pqy-1375427403.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/28564/original/2n4t2pqy-1375427403.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/28564/original/2n4t2pqy-1375427403.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/28564/original/2n4t2pqy-1375427403.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The new tool takes into account the age at birth of first child and number of children, which affect cancer risk.</span>
<span class="attribution"><span class="source">Image from shutterstock.com</span></span>
</figcaption>
</figure>
<p>There are two ways in which this tool could be used. First, the relative risk estimates show the impact each risk factor has on subsequent risk, and so could provide motivation of modify those risks. A woman who drinks at least one alcoholic drink per day has about a 25% greater risk of endometrial cancer than a teetotaller. So in terms of endometrial cancer risk, a woman is better off not drinking alcohol.</p>
<p>The second use is to estimate, based on a specific combination of risk factors, a woman’s risk (or probability) is of being diagnosed with one of these cancers in the next 20 years. These absolute estimates are <a href="http://www.qrisk.org/">often provided</a> through web-based dissemination tools, such as this one for cardiovascular disease. </p>
<p>At present, <a href="http://dceg.cancer.gov/tools/risk-assessment/br_en_oc_ram">it seems</a> the researchers of the tool have only made computer codes available for statistical software.</p>
<h2>The down sides</h2>
<p>The model has some shortcomings. These studies only include Caucasian women aged 50 years and over. So we cannot extrapolate the results to younger women, nor to women of other races or nationalities.</p>
<p>Also, the cohorts did not include all eligible women. The <a href="http://www.ncbi.nlm.nih.gov/pubmed/11744517">response rate</a> for the original study cohort, for example, was only 17.6% (approximately 570,000 out of 3.5 million people).</p>
<p>It is possible that the people who responded to the study had different characteristics to those who didn’t. They might have been healthier or more interested in health issues, both of which may impact on their risk of cancer and so on the final results.</p>
<p>The authors also acknowledge the models aren’t intended to predict the probability of the three cancers among women at much higher risk, such as those with the BRCA1 or BRCA2 mutations.</p>
<h2>How do the models perform?</h2>
<p>Performance is typically measured in two ways – calibration and discrimination.</p>
<p>Calibration measures how well the model, developed in the initial cohort, corresponds to the real outcome possibility: in this case, the observed proportion of cancer diagnoses in the second cohort.</p>
<p>In contrast, discrimination measures the ability of the model to predict a given outcome (that is, a cancer diagnosis) based on the combination of risk factors for a specific person.</p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/28565/original/d4zyqdsj-1375427720.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/28565/original/d4zyqdsj-1375427720.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=751&fit=crop&dpr=1 600w, https://images.theconversation.com/files/28565/original/d4zyqdsj-1375427720.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=751&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/28565/original/d4zyqdsj-1375427720.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=751&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/28565/original/d4zyqdsj-1375427720.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=944&fit=crop&dpr=1 754w, https://images.theconversation.com/files/28565/original/d4zyqdsj-1375427720.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=944&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/28565/original/d4zyqdsj-1375427720.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=944&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The model is only slightly better than tossing a coin at calculating the risk of breast and ovarian cancer for an individual woman.</span>
<span class="attribution"><span class="source">Image from shutterstock.com</span></span>
</figcaption>
</figure>
<p>In terms of calibration, the predictive risk model performed well. Although it over-estimated the overall risk of endometrial cancer by about 20%, the predicted risk for breast and ovarian cancers agreed closely with the observed risk.</p>
<p>Discrimination, however, was not so impressive. When considering that a value of 0.5 is analogous to tossing a coin, and 1.0 is perfect prediction, the discrimination values for breast cancer and ovarian cancer were 0.58 and 0.59 respectively. The predictive capacity for endometrial cancer was slightly better at 0.68.</p>
<h2>What these results mean in practice?</h2>
<p>These models provide important insights into the absolute burden of these cancers in a population of white women aged 50 years and over. It’s also useful in gauging the potential for how the population risk of cancer could be reduced using preventive interventions among this population.</p>
<p>But it’s not very effective at predicting individual woman’s risk of cancer. While the factors included in the statistical models explain some of the risk, there remain other unmeasured factors that dictate whether a woman will get one of these cancers. </p>
<p>This means that a woman might have none of the risk factors and still be diagnosed with breast cancer, or she might have all of the risk factors and not be diagnosed in the next 20 years. Given that there is still a lot to be learnt about the causes of most types of cancer, this conclusion is not really surprising.</p>
<p>The take-home message of this research is that there are measures by which women can reduce their risk of getting these types of cancer, and hopefully these results increase their motivation to do so.</p><img src="https://counter.theconversation.com/content/16584/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Peter Baade receives funding from the National Health and Medical Research Council (NHMRC).</span></em></p>Researchers in the United States have developed a new model to predict women’s risk of developing breast, uterine and ovarian cancer, based on individual lifestyle factors. These three cancers make up…Peter Baade, Senior Research Fellow, Cancer Council QueenslandLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/26892011-08-12T03:57:55Z2011-08-12T03:57:55ZBreast cancer screening – are women given all the facts?<figure><img src="https://images.theconversation.com/files/2858/original/aapone-20041014000012598198-mammography_machine-original.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Early detection means a better chance of successful treatment but are some women being treated unnecessarily?</span> <span class="attribution"><span class="source">AAP</span></span></figcaption></figure><p><a href="http://www.breastcanceraustralia.org/home.html">Breast cancer</a> is the most common cause of cancer-related death in Australian women. But experts disagree on the benefits of breast cancer screening programs, with some arguing that it’s unclear whether it does <a href="http://onlinelibrary.wiley.com/o/cochrane/clsysrev/articles/CD001877/frame.html">more harm than good</a>.</p>
<p>One in 11 women will be diagnosed with breast cancer before the age of 75. In Australia, as in many other developed countries, we have a screening program to detect breast cancer early because this offers the best chance of survival. </p>
<h2>Early detection programs</h2>
<p>The National Program for the Early Detection of Breast Cancer, now called BreastScreen Australia, was introduced in 1991. </p>
<p>The program encourages all women aged between 50 and 69 years without any signs or symptoms to have screening mammograms every two years. </p>
<p>Mammography uses X-ray to try to find early breast cancers before a lump can be felt. </p>
<p>The reason for screening asymptomatic women is that early detection in this age group is believed to offer a better chance of successful treatment and recovery.</p>
<p>Researchers from the <a href="http://www.bmj.com/content/338/bmj.b86.full">Nordic Cochrane Centre</a> and others are now questioning this reasoning. </p>
<p><a href="http://www.bmj.com/content/343/bmj.d4411.abstract">French researchers</a> for instance, have recently analysed data from breast cancer deaths registered in the <a href="http://www.who.int/healthinfo/morttables/en/index.html">World Health Organization mortality database</a>. </p>
<p>They compared three pairs of countries: Northern Ireland and the Republic of Ireland, the Netherlands and Belgium, and Sweden and Norway. </p>
<p>The country pairs are neighbours and similar in population structure, socioeconomic circumstances, quality of health-care services and access to treatment. </p>
<p>But they differ in the length of time they’ve had mammography screening programs. </p>
<p>In one half of each pair, the program has existed since around 1990, while the other country introduced it some years later.</p>
<p>The researchers found that between 1989 and 2006, trends in breast cancer mortality rates varied little between the pairs of countries.</p>
<p>They concluded that screening didn’t play a direct part in the reduction of breast cancer mortality.</p>
<p>How can this be explained, if early detection is supposed to lead to better detection, treatment and years of survival after diagnosis? </p>
<p>Well, some of the cancerous tumours detected through screening grow very slowly, or not at all. Indeed, some disappear if left untreated.</p>
<p>So some women receive a cancer diagnosis even though their tumours won’t necessarily lead to sickness or death. </p>
<p>These women experience needless anxiety and stress and are treated unnecessarily. </p>
<p>A systematic review of interventions <a href="http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001877.pub4/abstract;jsessionid=18D69F315F62E3D90AC518F2F1C54BF2.d03t03">published in the Cochrane Library</a> found that for every 2,000 women screened regularly for 10 years, one will avoid dying from breast cancer and have her life prolonged. </p>
<p>In addition, 10 healthy women, who wouldn’t have been diagnosed if they hadn’t participated in the screening program, will be diagnosed with breast cancer and treated unnecessarily. </p>
<p>These women have either a part or the whole of their breast removed, as well as often receiving radiotherapy and chemotherapy.</p>
<h2>So why do it?</h2>
<p>Unfortunately, medical science hasn’t yet discovered how to distinguish tumours that will lead to cancer from those that will disappear without treatment or cause no harm during the lifetime of a person. </p>
<p>But this isn’t explained to women when they are about to participate in breast cancer screening. The website of the <a href="http://www.health.gov.au/internet/screening/publishing.nsf/Content/faqs">BreastScreen Australia Program</a> notes a 25% fall in mortality since the introduction of mammography screening, but doesn’t mention the unnecessary pain and anguish that may be caused by the program. </p>
<p>Instead, a link to a <a href="http://canceraustralia.nbocc.org.au/our-organisation/position-statements/over-diagnosis-from-mammography-screening">National Breast and Ovarian Cancer Centre position statement</a> on over-diagnosis from mammography screening is provided. It is a technical statement and “not intended to be a decision-making aid for women considering screening”. </p>
<p>Women need to be given the existing evidence about benefits and harms of screening programs in a plain English statement and the opportunity to discuss the available evidence with their health-care provider. It is a necessary condition for informed consent. </p>
<p>After all, we expect to be provided with information about possible side effects of medical procedures and prescription drugs. So possible harms of screening procedures need to be disclosed as well.</p>
<p>The Nordic Cochrane Centre has developed a mammography screening leaflet that addresses the following questions:</p>
<ul>
<li><p>What are the benefits and harms of attending a screening program?</p></li>
<li><p>How many will benefit from being screened, and how many will be harmed?</p></li>
<li><p>What is the scientific evidence for this? </p></li>
</ul>
<p>The <a href="http://www.cochrane.dk/">leaflet</a> is available online in English and 12 other languages. BreastScreen Australia Program should either promote the use of this leaflet or develop its own. </p>
<p>Different people make different choices. Given all the information, some women may decide it’s reasonable for them to attend breast cancer screening with mammography. </p>
<p>Others may choose not to attend but all women need to know <em>all</em> the available facts to make an informed choice.</p><img src="https://counter.theconversation.com/content/2689/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Monika Merkes does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Breast cancer is the most common cause of cancer-related death in Australian women. But experts disagree on the benefits of breast cancer screening programs, with some arguing that it’s unclear whether…Monika Merkes, Honorary Associate, Australian Institute for Primary Care & Ageing, La Trobe UniversityLicensed as Creative Commons – attribution, no derivatives.