BRCA1 and BRCA2 (BRCA1/2) mutations account for most (though not all) cases of inherited breast cancer in women. These mutations are also associated with an increased risk for ovarian cancer. In men, BRCA1/2 mutations increase the risk for breast cancer and may also increase prostate cancer risk.  Research has indicated there may also be an increased risk of melanoma and pancreatic cancer in people with BRCA1/2 mutations.

Although BRCA1/2 mutations significantly increase the risk of cancer, having one of these mutations doesn’t mean a person actually has cancer or will necessarily ever get the disease.   But new research from scientists at the National Cancer Institute and the National Human Genome Research Institute, published online this week in the journal PLoS ONE, suggests that those BRCA1/2 carriers who do escape cancer may still be at risk of a shorter than average lifespan.

In a study of almost 5,300 people with Ashkenazi Jewish ancestry researchers found that, on average, both men and women who carry BRCA1/2 mutations die younger — even when cancer deaths are excluded from the analysis.  Among women free of melanoma, breast, ovarian and pancreatic cancer, BRCA1/2 mutation carriers died 5.8 years earlier (age 75.0 vs. 80.5) than those women without the mutations. In men, after excluding cases of melanoma, prostate and pancreatic cancer, BRCA1/2 mutation carriers died about 3.7 years earlier than those without the mutations (71.0 years old vs. 74.7).

“Theoretically, these mutations may either be associated with a small increase in risk of a variety of different diseases, or they may be associated with moderate increase in risk of a few major diseases,” the authors write.  They note that the current study is unable to make this distinction because it did not collect information on non-cancer related causes of death.

The researchers analyzed the effects of only the three BRCA mutations that are most common in Ashkenazi Jewish people: 185delAG in BRCA1, 5382insC in BRCA1, and 6174delT in BRCA2.  The mutations account for 80-90% of hereditary breast and ovarian cancer in this ethnic group.  But there are hundreds of other BRCA1/2 mutations that have been associated with cancer, and the authors caution that further studies taking these other BRCA1/2 mutations into account and using study subjects from diverse groups will be needed to confirm their results.

(23andMe provides data for the three BRCA1/2 mutations most commonly found in people with Ashkenazi Jewish ancestry in the BRCA Cancer Mutations (Selected) Carrier Status Clinical Report.)

The authors conclude that understanding the effects of BRCA1/2 mutations on non-cancer related deaths could eventually help scientists understand how the mutations affect cancer risk and may even facilitate efforts aimed at finding new ways of preventing disease in BRCA1/2 mutation carriers.

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There has been plenty of research in both genetics and archaeology recently trying to figure out how the New World was colonized. Was it by boat or via the frozen wasteland of the Bering Strait? Was it a fast trip down to South America, or did these first inhabitants take a more leisurely stroll? And when did all this happen anyway?

As each new study is published we are learning vital information on the peopling of the Americas. Ideas and theories continue to be retooled as new evidence comes to light.

This will certainly be the case with regards to a paper in the May 2008 issue of PLoS Genetics. In this article, researchers from Oxford and Cornell Universities report on a new computer model they have developed to trace prehistoric human migrations across the globe.

Using genetic information from various populations alive today, the authors estimated how those groups may be related to one another. Then they used those relationships to piece together the prehistoric movements of early humans.

As expected, their analysis showed a single migration out of Africa that eventually populated Eurasia and the Americas. However, the results for the Peopling of the Americas were more surprising.

The conventional wisdom states that the first inhabitants of the Americas came from Asia in a single wave more than 10,000 years ago. But when the authors compared the genetic data of two Native American groups (one in Colombia and one in the American Southwest) to groups in East Asia, what they found supported a two-wave migration.

The Colombian sample of Native Americans was actually more closely related to the East Asian sample than it was to the American Southwest sample. That suggests the two populations come from independent sources – and that there were at least two separate migrations of humans into the New World. Clearly, one of these migrations would have come from East Asia and made its way into South America. However, the data suggest a separate migration, probably from a different part of Asia or Siberia, came at a different time, and this time only made it to North America. This conclusion is significant, as it contradicts current theories on the topic, which argue a more constant flow of migrants from an original source somewhere in Asia.

There are still plenty of questions regarding this research, especially with regard to how it compares to the archaeological record and to previous genetic studies. The answers to these questions can only come with additional research, which, thankfully, is always forthcoming on the peopling of the Americas.

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