Targetable Mutations in Patients With Pancreatic Cancer Without Family History of Disease

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Only 3 of 33 patients with susceptibility germline mutations had a family history of pancreatic cancer; this was true among 117 of the 818 other patients without a germline mutation.
Only 3 of 33 patients with susceptibility germline mutations had a family history of pancreatic cancer; this was true among 117 of the 818 other patients without a germline mutation.

Some patients with pancreatic cancer harbor targetable deleterious germline mutations even when there is no family history of the disease, according to research published in the Journal of Clinical Oncology.1

Heritable mutations are linked to pancreatic cancer, which is expected to cause the most cancer-related deaths in the United States by 2030. Genes linked to the disease include BRCA2, ATM, PALB2, CDKN2A, PRSS1, STK11, MLH1, and MSH23. BRCA2 is the gene most often linked to familial pancreatic cancer risk; the mutation is most common in the Ashkenazi Jewish population.

For this prospective study, researchers determined the presence of germline mutations among patients with pancreatic cancer regardless of family history.

Among 854 patients with pancreatic cancer, 33 patients had deleterious germline mutations, the most common of which were BRCA2 (12 patients), ATM (10 patients), and BRCA1 (3 patients). Patients with these mutations, 31 of which are linked to pancreatic cancer susceptibility, were on average younger than other patients (60.8 vs 65.1 years, respectively).

Only 3 of the 33 patients with susceptibility germline mutations had a family history of pancreatic cancer; this was true among 117 of the 818 patients without a germline mutation. Among the 33 patients with germline mutations, 18 had a family history of breast cancer, 6 had a family history of prostate cancer, and 3 had a history of ovarian cancer.

RELATED: Hyperthermia Plus Chemotherapy May Be Effective in Pancreatic Cancer

The authors concluded that “there is a significant yield of deleterious germline mutations in pancreatic cancer susceptibility genes in unselected patients with apparently sporadic pancreatic cancer. Routine gene testing of patients with newly diagnosed pancreatic cancer and their families may yield significant clinical benefits.”

Reference

  1. Shindo K, Yu J, Suenaga M, et al. Deleterious germline mutations in patients with apparently sporadic pancreatic adenocarcinoma. J Clin Oncol. 2017 Aug 2. doi: 10.1200/JCO.2017.72.3502 [Epub ahead of print]

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