Colorectal and other cancer risks for carriers and noncarriers from families with a DNA mismatch repair gene mutation: a prospective cohort study

Reference details

Win AK, Young JP, Lindor NM, Tucker KM, Ahnen DJ, Young GP, Buchanan DD, Clendenning M, Giles GG, Winship I, Macrae FA, Goldblatt J, Southey MC, Arnold J, Thibodeau SN, Gunawardena SR, Bapat B, Baron JA, Casey G, Gallinger S, Le Marchand L, Newcomb PA, Haile RW, Hopper JL, Jenkins MA (2012) Colorectal and other cancer risks for carriers and noncarriers from families with a DNA mismatch repair gene mutation: a prospective cohort study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 30:958-964

ABTRACT

PURPOSE: To determine whether cancer risks for carriers and noncarriers from families with a mismatch repair (MMR) gene mutation are increased above the risks of the general population. PATIENTS AND METHODS: We prospectively followed a cohort of 446 unaffected carriers of an MMR gene mutation (MLH1, n = 161; MSH2, n = 222; MSH6, n = 47; and PMS2, n = 16) and 1,029 their unaffected relatives who did not carry a mutation every 5 years at recruitment centers of the Colon Cancer Family Registry. For comparison of cancer risk with the general population, we estimated country-, age-, and sex-specific standardized incidence ratios (SIRs) of cancer for carriers and noncarriers. RESULTS: Over a median follow-up of 5 years, mutation carriers had an increased risk of colorectal cancer (CRC; SIR, 20.48; 95% CI, 11.71 to 33.27; P < .001),="" endometrial="" cancer="" (sir,="" 30.62;="" 95%="" ci,="" 11.24="" to="" 66.64;="" p="">< .001),="" ovarian="" cancer="" (sir,="" 18.81;="" 95%="" ci,="" 3.88="" to="" 54.95;="" p="">< .001),="" renal="" cancer="" (sir,="" 11.22;="" 95%="" ci,="" 2.31="" to="" 32.79;="" p="">< .001),="" pancreatic="" cancer="" (sir,="" 10.68;="" 95%="" ci,="" 2.68="" to="" 47.70;="" p=".001)," gastric="" cancer="" (sir,="" 9.78;="" 95%="" ci,="" 1.18="" to="" 35.30;="" p=".009)," urinary="" bladder="" cancer="" (sir,="" 9.51;="" 95%="" ci,="" 1.15="" to="" 34.37;="" p=".009)," and="" female="" breast="" cancer="" (sir,="" 3.95;="" 95%="" ci,="" 1.59="" to="" 8.13;="" p=".001)." we="" found="" no="" evidence="" of="" their="" noncarrier="" relatives="" having="" an="" increased="" risk="" of="" any="" cancer,="" including="" crc="" (sir,="" 1.02;="" 95%="" ci,="" 0.33="" to="" 2.39;="" p=".97)." conclusion:="" we="" confirmed="" that="" carriers="" of="" an="" mmr="" gene="" mutation="" were="" at="" increased="" risk="" of="" a="" wide="" variety="" of="" cancers,="" including="" some="" cancers="" not="" previously="" recognized="" as="" being="" a="" result="" of="" mmr="" mutations,="" and="" found="" no="" evidence="" of="" an="" increased="" risk="" of="" cancer="" for="" their="" noncarrier="">

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