LYNCH SYNDROME AND PANCREATIC CANCER

NEW YORK (Reuters Health) Oct 27 - The risk of pancreatic cancer in families with Lynch syndrome is more than 8 times higher than in the general population, according to a paper in the October 28 issue of the Journal of the American Medical Association.

Lynch syndrome is an autosomal dominant disorder caused by defects in the mismatch repair (MMR) genes MLH1, MSH2, MSH6, or PMS2. The mutations increase patients' risk for colon cancer, endometrial cancer, and other neoplasms, Dr. Sapna Syngal of the Dana-Farber Cancer Institute in Boston and her colleagues note.

To quantify the pancreatic cancer risk associated with these mutations, Dr. Syngal and her team looked at 6,342 people from 147 Lynch syndrome families. Thirty-one families, or 21.1%, had one or more cases of pancreatic cancer affecting 21 men and 26 women.

The estimated relative risk of pancreatic cancer was particularly high for individuals aged 20 to 49 years (hazard ratio, 30.5). The hazard ratio decreased with age, to 5.1 for people 50 to 70 years old.

The absolute cumulative risk of developing pancreatic cancer was 1.31% at age 50 and 3.68% at age 70. By comparison, according to the article, the Surveillance, Epidemiology and End Results (SEER) database shows population-based cumulative incidences of 0.04% and 0.52% for ages 50 and 70 years, respectively.

"Pancreatic cancer is a clinically relevant component of Lynch syndrome and quantifying this risk for gene carriers should be incorporated into clinical management," the researchers say.

In an interview with Reuters Health, Dr. Syngal advised that physicians treating patients with pancreatic cancer ask whether other cancers run in the family. Patients who report a family history of colon or endometrial cancer -- and their family members -- should be tested for mutations that cause Lynch syndrome.

The effectiveness of using endoscopic ultrasound and computed tomography to monitor high-risk families for pancreatic cancer is being studied, Dr. Syngal said, but for now there is no way to prevent the disease in at-risk individuals. But, she added, individuals with any pancreatic cancer-associated mutations should quit smoking, because this is the one known lifestyle-related risk factor for the disease.

JAMA 2009;302:1790-1795.