Six Germline Mutations Uncovered of Increased Pancreatic Cancer Risk

June 20, 2018
Six Germline Mutations Uncovered of Increased Pancreatic Cancer Risk
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Only about 10% of all pancreatic cancer cases are associated with individuals that have a prior family history. Investigators at the Mayo Clinic have now uncovered clinical evidence suggesting that current testing guidelines miss genetic predisposition to cancer in the remaining 90% of pancreatic cancer patients. The researchers identified six genes containing mutations that may be passed down in families, substantially increasing a person's risk for pancreatic cancer. Findings from the new study—published recently in JAMA, in an article entitled “ Association Between Inherited Germline Mutations in Cancer Predisposition Genes and Risk of Pancreatic Cancer”—suggest that many people should have DNA testing to understand their risk for cancer.

"This study provides the most comprehensive data to date supporting genetic testing for all pancreatic cancer patients," noted senior study investigator Fergus Couch, Ph.D. chair of the division of experimental pathology and laboratory medicine at The Mayo Clinic. "This is the first study to provide estimates on the magnitude of cancer risk associated with each gene. It indicates that family history alone cannot predict who has these mutations."

In the current study, genetic testing was conducted on 3030 pancreatic patients who were seen at the Mayo Clinic between 2000 and 2016. The test results of 21 cancer genes were compared to equivalent results from more than 123,000 patients without pancreatic cancer. The research team found six genes clearly linked to an increased risk of pancreatic cancer: BRCA1, BRCA2, CDKN2A, TP53, MLH1, and ATM. These genetic mutations were identified in 5.5% of all pancreatic cancer patients, including 5.2% of cancer patients without a family history of pancreatic cancer.

“Multiple genes can each increase the risk of pancreatic cancer,” explained senior study author Gloria Petersen, Ph.D., professor of epidemiology at the Mayo Clinic. “But if genetic testing is performed only on patients with a family history of pancreatic cancer, then a small number of patients will be helped."

Patients who have these genetic mutations are at a substantially higher risk for pancreatic cancer, but that does not definitively mean they will develop the disease.

"The conclusion of this study is that we now have better molecular insights into the underlying genetic causes of pancreatic cancer," stated study author Raed Samara, Ph.D., global product manager at QIAGEN, who designed the DNA testing for this research. "The comprehensive data generated from this cohort required the specific and uniform sequencing and deep analyses of a focused set of cancer predisposition genes. The risks of developing pancreatic cancer due to mutations in these genes can be more accurately estimated than ever before because of this seminal study."

Often, pancreatic cancer is not diagnosed until late stages, when it has spread to other parts of the body. This year, 55,000 Americans will be diagnosed with pancreatic cancer, and 44,000 Americans will die of the disease this year, according to American Cancer Society estimates.