Carriers of MSH6 mutation at higher risk for colorectal, endometrial cancers

Carriers of the MSH6 mutation were at higher risk for colorectal and endometrial cancers and any cancer associated with Lynch syndrome by age 80.

Mutations in MSH6 account for 10% to 20% of Lynch syndrome, which causes colorectal and other cancers; however, less is known about cumulative cancer risk for people with this mutation, according to researchers.

To examine cumulative risk, researchers studied data from 113 families of MSH6 carriers. They gathered information on mutation status, sex, age, histories of cancer, polypectomy and hysterectomy from 3,140 relatives of the carriers.

At age 70 years, the risk for colorectal cancer was 22% in men with MSH6 mutations and 10% in women with the mutation. When aged 80 years, the risk for diagnosis of colorectal cancer was 44% for men with MSH6 mutations and 20% for women with MSH6 mutations.

The risk for endometrial cancer when aged 70 years was 26% in women carriers of MSH6; when aged 80 years, the risk was 44%.

Twenty-four percent of men with MSH6 mutations and 40% of women with MSH6 mutations were at risk for diagnosis of any Lynch syndrome cancer when aged 70 years. At 80 years, the risk increased to 47% in men with MSH6 mutations and 65% in women with MSH6 mutations.

Overall, carriers of the MSH6 mutation had an almost eightfold increased risk of any colorectal cancer compared with the general population (HR= 7.6; 95% CI, 5.4-10.8). However, women with MSH6 mutations had a 26-fold increased risk for endometrial cancer (HR=25.5; 95% CI, 16.8-38.7) and a sixfold increased risk of cancers linked to Lynch syndrome (HR=6.0; 95% CI, 3.4-10.7) when compared with the general population.

Baglietto L. J Natl Cancer Inst. 2009;doi:10.1093/jnci/djp473.