Cancer Risk in Hereditary Nonpolyposis Colorectal Cancer Syndrome: Later Age of Onset

摘要: Background & Aims: Mutations in the mismatch repair genes cause hereditary nonpolyposis colorectal cancer (HNPCC) syndrome and convey high lifetime risks for (CRC) endometrial cancer. Currently, individuals with HNPCC are based on data from clinically ascertained families. The purpose of this study was to re-examine penetrance using a comprehensive dataset geographically defined region. Methods: A combined 70 families by traditional high-risk criteria molecular screening comprising 88 probands 373 mutation-positive family members used. Statistical methods were modified survival analysis techniques. Results: In relatives (excluding probands), median age at diagnosis CRC 61.2 years (confidence interval [CI], 56.3–68.0 y). risk 68.7% (CI, 58.6%–78.9%) men 52.2% 37.6%–66.9%) women. Considering only probands, 44.0 41.0–46.3 Median onset EC 62.0 55.9 y an upper limit too calculate) 54% 41.9%–66.1%). Conclusions: markedly later 61 than previously reported (∼44 y) is suggested, resulting mainly more rigorous method which all gene-positive (both affected unaffected cancer) considered. Lifetime may be lower presently assumed. If confirmed, these suggest need alter counseling practices, consider older before.