Cancer risk in mutation carriers of DNA-mismatch-repair genes - PubMed (original) (raw)
Cancer risk in mutation carriers of DNA-mismatch-repair genes
M Aarnio et al. Int J Cancer. 1999.
Abstract
Excessive incidence of various cancers is a challenging feature of the hereditary-non-polyposis-colorectal-cancer (HNPCC) syndrome. This study estimated the cancer incidences in HNPCC compared with the general population. Individuals in a cohort of 1763 members of 50 genetically diagnosed families were categorized according to their genetic status as mutation carriers, non-carriers, or individuals at 50 or 25% risk of being a carrier. Incidences of cancers in these groups were compared with those in the Finnish population overall. In 360 mutation carriers, standardized incidence ratios (SIR) were significantly increased for colorectal [68; 95% confidence intervals (CI), 56 to 81], endometrial (62; 95% CI, 44 to 86), ovarian (13; 95% CI, 5.3 to 25), gastric (6.9; 95% CI, 3.6 to 12), biliary tract (9.1; 95% CI, 1.1 to 33), uro-epithelial (7.6; 95% CI, 2.5 to 18) and kidney (4.7; 95% CI, 1 to 14) cancers and for central-nervous-system tumours (4.5; 95% CI, 1.2 to 12). The SIR increased with increasing likelihood of being a mutation carrier. The cumulative cancer incidences were 82, 60, 13 and 12% for colorectal, endometrial, gastric and ovarian cancers respectively. For other tumours associated with increased risk, corresponding incidences were below 4%. Interestingly, the incidence of endometrial cancer (60%) exceeded that for colorectal cancer in women (54%). The tumour spectrum associated with germline mutations of DNA-mismatch-repair genes involves 8 or more organ sites, suggesting a need to develop methods to screen for extra-colonic cancer also.
Comment in
- Preparing for the unexpected: encountering gynecological problems when operating for colon cancer.
Dowdy SC, Cliby WA. Dowdy SC, et al. Curr Surg. 2003 Jan-Feb;60(1):12-16. doi: 10.1016/s0149-7944(02)00746-8. Curr Surg. 2003. PMID: 15214315 No abstract available.
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