Inherited Gene Mutations and Pancreatic Cancer

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Study Links Six Inherited Genetic Mutations To Increased Risk of Pancreatic Cancer

Written By Carlin Kuhlmann
October 8, 2018

We know cancer is caused by genetic mutations, alterations or errors in the DNA within our cells that stop them from functioning normally. While the majority of these mutations are “somatic” – those that occur after conception – up to 10% of all cancer cases, including 10-15% of pancreatic cancer cases, are caused by mutations inherited from our mother or father, which are known as germline mutations.

A study published in June 2018 in the Journal of the American Medical Association (JAMA) by a team of researchers at the Mayo Clinic identified six inherited genetic mutations that increase an individual’s risk for developing pancreatic cancer.[1]

The study recommends that all patients with pancreatic cancer undergo genetic testing, not just those with a family history of the disease, to determine if an inherited genetic mutation is present, which could not only impact their treatment plan, it could also imply an increased risk of pancreatic cancer for the patient’s family members.

Genetic Mutations and Pancreatic Cancer

According to the JAMA study, mutations in six genes – BRCA 1, BRCA 2, CDKN2A, TP53, MLH1, and ATM- were identified in 5.5% of patients with pancreatic cancer, including 5.2% of patients who did not have a family history of pancreatic cancer.

Mutations in these six genes are often associated with hereditary cancer syndromes that can increase an individual or family’s risk for one or more types of cancer including pancreas cancer.

Lynch Syndrome, for example, is an inherited genetic condition linked to mutations in several genes including MLH1 along with other criteria. It is estimated that as many as 1 in 300 people may be carriers of a gene mutation associated with Lynch Syndrome[2], increasing their risk for multiple different types of cancer including colorectal, breast, endometrial (uterine), ovarian, and prostate[3]. Individuals with Lynch Syndrome are twice as likely as the general population to develop pancreatic cancer.[4]

Li-Fraumini Syndrome, another inherited cancer syndrome, is linked to several gene mutations, most commonly a mutation in the TP53 gene. Though Li-Fraumini Syndrome is rare (some estimates note as few as 1 in 20,000 individuals are affected), an individual with Li-Fraumini Syndrome carries a lifetime risk of 90% for developing any type of cancer, half of which are diagnosed before age 30.[5]

BRCA 1 and BRCA 2 mutations are most commonly associated with increased risk of breast and ovarian cancer, and also increase risk for pancreatic cancer. BRCA 1 carriers are twice as likely and BRCA 2 carriers are three times more likely to develop pancreatic cancer.

Learn More About BRCA 1 and BRCA 2 and Pancreatic Cancer

A mutated CDKN2A gene also has implications for multiple cancers. Carriers are at greater risk of developing both pancreatic cancer and melanoma.[6]

According to a team of researchers at Johns Hopkins University, an inherited mutation in the ATM gene is present in 2-3% of individuals with familial pancreatic cancer.[7]

Other gene mutations and inherited syndromes have also been associated with increased risk for pancreatic cancer including familial pancreatitis typically caused by mutations in the PRSS1 gene, Peutz-Jeghers syndrome caused by defects in the STK11 gene, and Von Hippel-Lindau Syndrome caused by mutations in the VHL gene. Pancreatic neuroendocrine tumors (PNETs) have been linked to inherited mutations in the NF1 gene and the MEN1 gene.[8] Research into the genetics of pancreatic cancer is ongoing.

Knowledge is Power and Control Over Your Own Healthcare

There is currently not an effective screening method for pancreatic cancer for the general population, but individuals and families who are predisposed to the disease due to inherited genetic mutations or inherited familial cancer syndromes may benefit from screening and surveillance as guided by physician specialists. Screening plans may involve regular MRIs, endoscopic ultrasounds, and tumor marker blood tests designed to detect cancer at the earliest stage possible when the chance for cure is greatest.

If you have a family history of cancer or family members diagnosed with cancer at a young age and would like to understand your hereditary cancer risk, it is best to start by scheduling an appointment with a genetic counselor or talking with your physician. It is important to note that not all individuals who carry a genetic mutation in one of these genes will ultimately develop pancreatic cancer. A genetic counselor or medical geneticist can help patients understand if genetic testing is right for them as well their individual risk based on test results.

Read More About Genetic Counseling and Genetic Testing

Related Information

Mutated Genes BRCA 1 and 2 Increases Risk of Pancreatic Cancer

Genetic Testing and Genetic Counseling

Getting Pancreatic Cancer is Mostly Random Bad Luck of Cell Mutations

What Causes Pancreatic Cancer

Pancreas Cancer Risk Factors

Symptoms of Pancreatic Cancer

Minimizing Your Chance of Getting Pancreatic Cancer


[1] Hu, C, Hart, S, Polley, E. Association Between Inherited Germline Mutations in Cancer Predisposition Genes and Risk of Pancreatic Cancer. JAMA 2018;319(23):2401-2409.

[2] https://www.cancer.net/cancer-types/lynch-syndrome

[3] https://www.cancer.net/cancer-types/lynch-syndrome

[4] http://columbiasurgery.org/pancreas/genetics-pancreatic-cancer

[5] https://www.cancer.net/cancer-types/li-fraumeni-syndrome

[6] McWilliams, R, Wieben, E, Rabe, K, Pedersen, K, Wu, Y, Sicotte, H, Petersen, G. Prevalence of CDKN2A Mutations in Pancreatic Cancer Patients: Implications for Genetic Counseling. European Journal of Human Genetics 2011; 19(4): 472-478.

[7] http://pathology.jhu.edu/pc/basicheredity.php?area=ba

[8] https://www.cancer.org/cancer/pancreatic-cancer/causes-risks-prevention/risk-factors.html

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