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Cancer risk in mutation carriers of DNA‐mismatch‐repair genes
Author(s) -
Aarnio Markku,
Sankila Risto,
Pukkala Eero,
Salovaara Reijo,
Aaltonen Lauri A.,
de la Chapelle Albert,
Peltomäki Päivi,
Mecklin JukkaPekka,
Järvinen Heikki J.
Publication year - 1999
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19990412)81:2<214::aid-ijc8>3.0.co;2-l
Subject(s) - medicine , lynch syndrome , endometrial cancer , cancer , colorectal cancer , oncology , population , ovarian cancer , germline mutation , incidence (geometry) , dna mismatch repair , gastroenterology , mutation , biology , genetics , gene , physics , environmental health , optics
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. Int. J. Cancer 81:214–218, 1999. © 1999 Wiley‐Liss, Inc.