Cancer Risks for the Relatives of Colorectal Cancer Cases with a Methylated MLH1 Promoter Region: Data from the Colorectal Cancer Family Registry

Blogger's Note: focus on MLH1

".....The cohort consisted of 3,128 first- and second-degree relatives of the 233 MLH1-methylated CRC cases with no MMR or MUTYH gene mutations.

The standardized incidence ratio (SIR) for CRC was 1.60 [95% confidence interval (CI), 1.22–2.16] for first-degree relatives and 1.08 (0.74–1.60) for second-degree relatives.

The SIR for gastric cancer was 2.58 (1.52–4.71) for first-degree relatives and 4.52 (2.23–10.61) for second-degree relatives and, for ovarian cancer, it was 2.16 (1.29–3.86) for first-degree relatives.

The risk of liver cancer was also increased significantly in first-degree relatives but the estimate was on the basis of only two cases.

These data imply that relatives of CRC cases with MLH1 methylation may be at increased risk of CRC and stomach cancer and possibly ovarian and liver cancer, suggesting that there may be a heritable factor for CRC and other cancers associated with MLH1 methylation in non–Lynch syndrome."