Multiple rare variants in different genes account for multifactorial inherited susceptibility to colorectal adenomas

Abstract

Clear-cut inherited Mendelian traits, such as familial adenomatous polyposis or hereditary nonpolyposis colorectal cancer, account for I1307K and E1317Q, and variants were also sought in AXIN1 (axin), CTNNB1 (β-catenin), and the mismatch repair genes hMLH1 and hMSH2. The control group consisted of 483 random controls. Thirty of 124 (24.9%) patients carried potentially pathogenic germ-line variants as compared with 55 (≈12%) of the controls. This overall difference is highly significant, suggesting that many rare variants collectively contribute to the inherited susceptibility to colorectal adenomas.