After hMSH2 and hMLH1--what next? Analysis of three-generational, population-based, early-onset colorectal cancer families.

摘要: The aim of our study was to examine the role genetic factors on early-onset colorectal cancer after excluding impact germline mutations in two major mismatch repair genes. A total 131 incident probands, under 45 years at diagnosis a first primary selected from Victorian Cancer Registry, and their first-and second-degree relatives, were interviewed. Germline DNA all 12 probands with family history meeting modified Amsterdam Criteria for Hereditary Non-Polyposis Colorectal (HNPCC) random sample 31 remaining screened hMSH2 hMLH1 via manual sequencing. identified 6 (5%), "HNPCC" families. Of 125 51 (41%) reported least one first-or relative an excess first-degree relatives (SMR = 2.7, 95% CI 1.7-4.1, p < 0.001). lifetime risk age 70 8.0% (5.0-12.8%), compared population 3.2% (p 0.01). best fitting gene model recessively-inherited 98% (95% 24-100%) carried by 0.17% would explain 15% cases before 45. Early-onset is strongly familial even families found be segregating mutation either 2 There evidence yet genes associated high cancer.