Is a gene mutation causing younger breast cancer cases?

Are gene mutations, environmental factors or better detection methods behind cases of women being diagnosed with cancer earlier in life than their mothers and aunts? Flickr/Pulpolux

Women who carry genes that predispose them to getting cancer at a young age may be passing the gene onto the next generation and causing cancers to develop at ever younger ages, a new study has found.

However, better detection methods or environmental factors may also be behind the earlier age-of-diagnosis, experts have said.

Scientists already knew that women with a mutation in genes known as BRCA1 and BRCA2 are more likely to develop breast or ovarian cancer at younger ages that women with no mutation.

However, until now, it has not been clear whether passing the gene onto the next generation was causing a compound effect, with each generation being diagnosed with cancer earlier in life.

To find out, researchers from the University of Texas MD Anderson Cancer examined data on 106 women who had breast cancer and BRCA gene mutations and a family member in the previous generation who also had a BRCA-related cancer.

The researchers discovered that the average age of diagnosis in the older generation was 48 years, compared with 42 years in the younger generation.

The researchers also conducted mathematical modelling that included a broader range of factors and concluded that younger generations are expected to develop cancer as much as 7.9 years earlier in life than women in older generations.

“Breast and ovarian cancers in BRCA mutation carriers appeared to be diagnosed at an earlier age in later generations,” the researchers wrote in their paper, titled “Earlier Age of Onset of BRCA Mutation-Related Cancers in Subsequent Generations” and published today in the journal Cancer.

Professor Rodney Scott, a cancer expert from the University of Newcastle’s School of Biomedical Sciences and Pharmacy, said the results were interesting but that other factors may be influencing the younger age of cancer diagnosis.

“My concern is it may well be reflecting an environmental change rather than a real genetic change,” he said.

“The other major contributing factor is the fact that diseases are being diagnosed at much earlier ages now. What you may be seeing is much better detection of diseases now than in earlier generations.”

Hard to prove

Associate Professor Clare Scott, a cancer expert from the Walter and Eliza Hall Institute of Medical Research, said environmental factors and study design flaws made it hard to prove that gene mutations were causing cancer to occur earlier in subsequent generations.

“There are some limitations of the study design, alluded to by the authors, particularly that the ages of cancers in family members were provided by the study participant and were not verified by the investigators,” she said.

However, Professor Scott noted that the researcher’s conclusions echoed findings in another study published by the journal PLoS Genetics in July this year.

In practice, doctors routinely recommend screening for breast cancer from at least five to 10 years prior to the age of the earliest cancer occurring in a family, she said.

“In fact, our routine recommendation is screening commencing from the age of 25 years, which in most cases is at least five years prior to the earliest age of breast cancer in these families, as breast cancer under the age of 30 in families with BRCA1 or BRCA2 mutations is very uncommon,” she said.

“The finding of genetic anticipation should certainly underpin these recommendations for screening to commence at the early ages described above. As screening is not currently uniformly taken up by all women at risk in these families, this information may improve the uptake of screening for breast cancer and prevention strategies for ovarian cancer.”

The University of Texas researchers behind the study published today in Cancer acknowledged that further research was needed to rule out “race, exposures, and other environmental factors, that were not available as part of our analysis.”

“Furthermore, improvements in imaging techniques, such as digital mammography and dedicated breast magnetic resonance imaging, may help diagnose [cancers] earlier in more recent generations,” they wrote.