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Carriers of MLH1 and MSH2 mutations have higher cancer risk than carriers of MSH6 mutations

Tuesday, June 7, 2011 (Last Updated: 06/08/2011)

TUESDAY, June 7 (HealthDay News) -- In families with Lynch syndrome, carriers of MLH1 and MSH2 mutations have an increased risk of cancer incidence compared to carriers of an MSH6 mutation, according to a study published in the June 8 cancer-themed issue of the Journal of the American Medical Association to coincide with the annual meeting of the American Society of Clinical Oncology, held from June 3 to 7 in Chicago.

Valérie Bonadona, M.D., Ph.D., of the Centre National de la Recherche Scientifique in Villeurbanne, France, and colleagues investigated the age-specific cumulative cancer risks associated with mutations in the MLH1, MSH2, and MSH6 genes, in 537 families with Lynch syndrome. A total of 248 participants with MLH1, 256 with MSH2, and 33 with MSH6 were included in the analyses.

The investigators identified significant differences in estimated cumulative cancer risk between carriers of the three mutated genes. By age 70 years, the estimated cumulated cancer risks for colorectal cancers were 41 percent for carriers of the MLH1 mutation, 48 percent for MSH2, and 12 percent for MSH6. The estimated cumulated risks for endometrial cancer by age 70 years were 54, 21, and 16 percent for MLH1, MSH2, and MSH6 carriers, respectively. For ovarian cancer, the risks were 20, 24, and 1 percent for MLH1, MSH2, and MSH6 carriers, respectively. Irrespective of the gene mutation, the estimated cumulative cancer risk by age 40 years did not exceed 2 percent for endometrial cancer or 1 percent for ovarian cancer, and the estimated lifetime risk for other tumors did not exceed 3 percent.

"MSH6 mutations are associated with markedly lower cancer risks than MLH1 or MSH2 mutations," the authors write.

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Specialties Hematology & Oncology
Gastroenterology
Pathology
OBGYN & Women's Health

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