Jan 15, 2009 - Research

Variation in DNA Repair Genes May Increase Risk for Pancreatic Cancer

The cells in our bodies are subject to a constant onslaught of potentially damaging chemicals. Some of these come from the environment — the toxins in cigarette smoke, for an example — while others are natural byproducts of cellular life. Regardless of their origin, these chemicals have the potential to cause serious DNA damage that can eventually result in cancer.

Cells have evolved numerous mechanisms for defusing the danger posed by these chemicals. In the event that these efforts fail and DNA damage does occur, cells also have their own DNA repair systems. Not surprisingly, mutations in the genes that encode these DNA-fixers can leave cells vulnerable and increase the chances that a cancer will develop. Bloom’s syndrome, Fanconi anemia and hereditary breast cancers caused by BRCA mutations are all examples of cancer syndromes caused by relatively rare functional mutations in DNA repair genes.

Research from the University of Texas M.D. Anderson Cancer Center in Houston published online today in Clinical Cancer Research shows that common variations, not just rare mutations, in DNA repair genes can increase the risk for pancreatic cancer.

Pancreatic cancer is the fourth leading cause of cancer death for both men and women in the United States. Environmental factors such as smoking, obesity, diabetes, chronic pancreatitis and dietary factors are known to play a part in determining the risk of pancreatic cancer, but about 10% of patients have a family history of the disease, suggesting that there are also genetic risk factors.

Donghui Lie and colleagues examined variations in several DNA repair genes among 734 non-Hispanic white pancreatic cancer patients and 780 people without the disease. They found that having two copies of the A version of rs1801516 in the ATM gene increased the odds of pancreatic cancer 2.76 times compared to two Gs. Having just one copy of the A version did not significantly increase risk.

SNPs in the ATM gene have also been associated with an increased risk of developing breast cancer. The protein encoded by ATM is known to be crucial for the cellular response to DNA damage.

The researchers also found a significant association between having two copies of the A version of rs2074522 in the LIG3 gene (also involved in DNA repair) and risk for pancreatic cancer. 23andMe does not currently provide data on this SNP.

“Pancreatic cancer is a highly fatal disease because most of the cases are diagnosed at late stage and the tumors are resistant to most therapies. Early detection for pancreatic cancer is crucial to reduce the mortality,” the authors write.

“However, there is no screening method available to identify the high-risk individuals among those at risk,” they write — referring to people such as smokers, people with diabetes, and those with a family history of pancreatic cancer.

The authors suggest that in addition to aiding in the development of screening tests for pancreatic cancer, finding and understanding variants such as those identified in their study will help aid in developing new treatments.

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