Skin carcinomas linked to increased risk of other cancers

Susceptibility to non-melanoma skin cancer doesn’t just come from too much time in the sun. Monkey.net/Flickr, CC BY-NC-SA

Non-melanoma skin cancers (NMSCs) are the most common cancers in Australia and account for seven out of every eight new cancers diagnosed. If detected early, they are relatively easy to treat and rarely spread to other parts of the body.

But new research by my colleagues and I, published today in the American journal Cancer Epidemiology, Biomarkers & Prevention, shows that people who get non-melanoma skin cancers – particularly before the age of 25 – are at a much greater risk of developing 30 other cancers, including breast, colon and lung cancers.

What are non-melanoma skin cancers?

Melanomas are the most dangerous form of skin cancer but only account for fewer than 2% of all skin cancers.

There are two main types of non-melanoma skin cancers: basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Both arise from the epidermis, the upper layer of the skin and appear as a flesh-coloured nodule on the skin or a sore that fails to heal. As their names suggest, BCCs come from the basal cells and SCCs from squamous cells.

Basal cell carcinoma. National Cancer Institute, CC BY

BCC remain confined to the skin, while SCC can metastasise to other parts of the body, though this is uncommon. While there were more than 800,000 NMSC treated in Australia in 2011, only 543 Australians died from NMSCs that year.

Broadly speaking, cancer develops from unrestrained cell growth and impaired cell function; normal functioning cells are progressively squeezed out and replaced by dysfunctional cancer cells.

The immune system normally eradicates these dysfunctional cells. And a number of mechanisms regulate cell growth, cell development and also immune surveillance of cancer. Cancer develops when these mechanisms are disrupted.

Different cancers result from disruption of different molecular pathways, and we now recognise there are shared molecular mechanisms for cancers of the epithelial cells (skin, salivary glands breast, bowel, lung) and also between BCC and certain brain tumours. Disruption of one of these shared molecular pathways may lead to multiple cancers in different organs.

Like melanoma, NMSC develops in susceptible people – those with fair skin, red or blond hair, blue eyes and those susceptibility to cancer in general – as a result of UV exposure.

Red heads are at greater risk of skin cancer. Shutterstock

We’ve known for some time that sunlight suppresses the skin immunity – that’s why some people get a cold sore during a holiday in the sun. This is because UV exposure suppresses the immune system in a number of specific ways: one is to allow herpes virus reactivation (a cold sore).

Another is to suppress tumour surveillance by the immune system. This is the natural protective mechanism the body uses to fight developing skin cancers.

Risk of other cancers

Before we undertook our study, we hypothesised that people who developed skin cancers later in life did so as a result of accumulated sun exposure, while those who developed skin cancer at a younger age did so because of an increased susceptibility to cancer in general.

To investigate this, we stratified the risk ratios by age and discovered that young people with NMSC were more cancer-prone.

Using data from the All England Record-linked Hospital and Mortality data set collected between 1999 and 2011, we constructed two cohorts: a group of 502,490 people with a history of NMSC, and another made up of 8.8 million people who served as controls.

We followed up with the participants electronically for five to six years, and found 67,148 from the NMSC group (13.36%) and 863,441 from the control group (9.81%) subsequently developed cancers.

We found that for those who had NMSC, the relative risk for developing cancers of the bladder, brain, breast, colon, liver, lung, pancreas, prostate, and stomach remained consistently elevated when compared to the control group for the entire period of the study, and the risk for cancers of the brain, colon, and prostate increased with time.

We also identified that those who had NMSC before the age of 25 were 53 times more likely to get bone cancer, 26 times more likely to get blood cancers, 20 times more likely to get brain cancer, and 14 times more likely to get any cancer excluding those of the skin.

The risk for developing any cancer subsequent to NMSC decreased with increasing age: 23 times higher risk for those under 25 years of age, 3.52 for those 25-44 years of age, 1.74 for those 45-59 years of age, and 1.32 for those older than 60 years.

So, although the risk decreased with increasing age, it remained higher compared with those who never had NMSC.

A 50-year pack-a-day smoker’s cancer risk is 25 times higher than a non-smoker’s. Shutterstock

The increased risk is significant. By way of comparison, the relative risk of developing lung cancer after smoking a packet of cigarettes a day for 50 years is 25.

Our study shows that NMSC susceptibility is not only a marker of people who have spent too much time in the sun. It is also an important indicator of susceptibility to malignant tumours – and the risk is especially high among people who develop NMSC at a young age.

Knowing your risk

Currently there are no clear guidelines for skin cancer screening.

The Cancer Council recommends opportunistic screening; in other words, when you see your GP for a cold, ask him or her to do a skin check at the same time. But many people who recognise they’re at higher risk of skin cancer attend regular check ups with their dermatologist.

People concerned about skin cancer or who have a new lump on their skin or a sore that won’t heal should seek medical advice from their GP initially, who can arrange referral to a dermatologist, if required.

More broadly, cancer screening works best if you know who to look at and what to look for. The recognition that NMSC patients are cancer-prone individuals, especially when diagnosed with their skin cancer at a young age, allows public health agencies to examine options to better target cancer screening.

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