JAMA Logo Lynch syndrome is a hereditary cancer syndrome that supposedly carries a high risk of colon cancer and an above-normal risk of other cancers. A recent study has now identified mutations linked with a lower cancer risk and mutations associated with an increased risk for ovarian and endometrial cancer. The study findings may help detect the exact target population for surgery and address the issue of optimum age.

During the study, authors thoroughly scrutinized specific cancer risks associated with mutations in the genes MLH1, MSH2, and MSH6 by examining a large sample of families with Lynch syndrome. The investigations engulfed 537 families with segregating mutated genes, 248 with MLH1, 256 with MSH2; and 33 with MSH6. These families were enrolled between January 2006 and December 2009 from 40 French cancer genetics clinics. In conclusion, significant differences in estimated cumulative cancer risk between the 3 mutated genes was registered.

Authors share, “For colorectal cancer, the estimated cumulative risks by age 70 years were 41 percent for MLH1 mutation carriers, 48 percent for MSH2, and 12 percent for MSH6. The estimated cumulative risks in carriers did not begin to increase until age 30 years, irrespective of gene mutation. For endometrial cancer, the estimated cumulative risks by age 70 years were 54 percent for MLH1, 21 percent for MSH2, and 16 percent for MSH6. By age 40 years, the estimated cumulative risk did not exceed 2 percent, irrespective of gene mutation. For ovarian cancer, the estimated cumulative risks by age 70 years were 20 percent for MLHl, 24 percent for MSH2, and 1 percent for MSH6. By age 40 years, the estimated cumulative risk did not exceed 1 percent, irrespective of gene mutation.”

Overall, for other Lynch syndrome-associated cancers, the estimated cumulative risks by age 70 years probably did not exceed 3 percent. This figure allegedly remained consistently low among families with the MSH6 mutations than in those carrying the other gene mutations. Valerie Bonadona, M.D., Ph.D., of the Centre National de la Recherche Scientifique, Villeurbanne, France, and colleagues believe that the results can possibly help understand the phenotypic differences between the MSH6, MLH1 or MSH2 mutation carriers.

The study is published online and in the June 8 issue of JAMA.