Families with germline MMR gene mutations had increased risk for pancreatic cancer

Families with a history of Lynch syndrome, which is caused by pathogenic MMR gene mutations, had nearly ninefold the risk for developing pancreatic cancer compared with the general population, according to newly published results.

Researchers used information collected from databases maintained by Dana-Farber Cancer Institute and the University of Michigan Comprehensive Cancer Center to evaluate the cancer histories of 147 families with Lynch syndrome.

The families had deleterious mutations in MLH1 (n=55), MSH2 (n=81) or MSH6 (n=11). Researchers found pathogenic gene mutations in 302 of the 6,342 individuals in the study.

There were 13 pancreatic cancers in the MLH1 families, 31 in the MSH2 families and three in the MSH6 families. Thirteen families had more than one incidence of cancer and 62% of those families had the MSH2 mutation.

Overall, families with any MMR gene mutation had a HR of 8.6 for developing pancreatic cancer (95% CI, 4.7-15.7) compared with the general population.

Specifically, carriers of MLH1 mutations had an estimated HR of 7.5 (95% CI, 2.4-23.0) for developing pancreatic cancer compared with an HR of 10.9 (95% CI, 5.5-21.9) for MSH2 carriers. Researchers did not calculate risk for MSH6 carriers because of the small number of cancers associated with the mutation.

When the researchers stratified risk by age, they found that risk was greatest among those aged 20 to 49 years (HR=30.5; 95% CI, 14.2-65.7) and it decreased with increasing age.

The absolute cumulative risk for developing pancreatic cancer in mutation carriers aged 50 years was 1.31% (95% CI, 0.31%-2.32%) and 3.68% at 70 years (95% CI, 1.45%-5.88%).

Kastrinos F. JAMA. 2009;302:1790-1795.