Does risk of endometrial cancer for women without a germline mutation in a DNA mismatch repair gene depend on family history of endometrial cancer or colorectal cancer?

Bharati R, Jenkins MA, Lindor NM, Le Marchand L, Gallinger S, Haile RW, Newcomb PA, Hopper JL, Win AK (2014) Does risk of endometrial cancer for women without a germline mutation in a DNA mismatch repair gene depend on family history of endometrial cancer or colorectal cancer? Gynecologic oncology 133:287-292

OBJECTIVE: To determine whether risk of endometrial cancer for women without a germline mutation in a DNA mismatch repair (MMR) gene depends on family history of endometrial or colorectal cancer. METHODS: We retrospectively followed a cohort of 79,166 women who were recruited to the Colon Cancer Family Registry, after exclusion of women who were relatives of a carrier of a MMR gene mutation. The Kaplan-Meier failure method was used to estimate the cumulative risk of endometrial cancer. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for association between family history of endometrial or colorectal cancer and risk of endometrial cancer. RESULTS: A total of 628 endometrial cancer cases were observed, with mean age at diagnosis of 54.4 (standard deviation: 15.7) years. The cumulative risk of endometrial cancer to age 70 years was estimated to be 0.94% (95% CI 0.83-1.05) for women with no family history of endometrial cancer, and 3.80% (95% CI 2.75-4.98) for women with at least one first- or second-degree relative with endometrial cancer. Compared with women without family history, we found an increased risk of endometrial cancer for women with at least one first- or second-degree relative with endometrial cancer (HR 3.66, 95% CI 2.63-5.08), and for women with one first-degree relative with colorectal cancer diagnosed at age <50 years="" (hr="" 1.48,="" 95%="" ci="" 1.15-1.91).="" conclusion:="" an="" increased="" risk="" of="" endometrial="" cancer="" is="" associated="" with="" a="" family="" history="" of="" endometrial="" cancer="" or="" early-onset="" colorectal="" cancer="" for="" women="" without="" a="" mmr="" gene="" mutation,="" indicating="" for="" potential="" underlying="" genetic="" and="" environmental="" factors="" shared="" by="" colorectal="" and="" endometrial="" cancers="" other="" than="" caused="" by="" mmr="" gene="">