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?

Abstract

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 mutations.

Identifying High-Risk Women for Endometrial Cancer Prevention Strategies: Proposal of an Endometrial Cancer Risk Prediction Model

“…57). This risk is increased further if 2 or more first-or second-degree relatives have previously had endometrial cancer (HR, 8.73; 95% CI, 4.25-17.9; P < 0.001).…”

Ellagic acid regulates Wnt/β-catenin signaling pathway and CDK8 in HCT 116 and HT 29 colon cancer cells

“…Colon cancer carcinogenesis has been reported to be associated with genetic errors in genes involved in apoptosis and cell proliferation (Davies et al, 2005;Watson, 2006;Damaschke et al, 2013;Bharati et al, 2014). Genetic defects triggering aberrant activation of Wnt/ -catenin signalling are common and are reported in over 90% of sporadic cases of colon cancer (Miyaki et al, 1994;Clevers, 2006;Klaus and Birchmeier, 2008;Schon et al, 2014).…”

Family History and Risk of Endometrial Cancer

“…3 Several studies have reported an increased risk of endometrial cancer for women with at least one firstdegree relative (mother, sisters, or daughters) affected with endometrial cancer; however, risk estimates have been inconsistent. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] Furthermore, some studies have estimated associations of risk of endometrial cancer with familial clustering of cancers of the colon, rectum, breast, ovary, and cervix, and these estimates have also been inconsistent. [4][5][6][7][8][9][10][12][13][14][15]17,23,24 Despite the attention directed toward the potential role of family history in endometrial cancer risk, quantification of relative risk (RR) of cancer specific to site in first-degree relatives has not been adequately determined.…”

“…Of the 10 case-control studies, four used hospital attendees without any cancer diagnosis as control participants. 4,8,12,13 Five studies estimated risk of endometrial cancer associated with a family history of cancer up to seconddegree relatives 9,13,14,17,23 and one study estimated risk up to third-degree relatives. 16 Of the 14 studies that reported an association between a family history of endometrial cancer and risk of endometrial cancer, 4-17 nine reported clear evidence for an increased risk of endometrial cancer for women with at least one first-degree relative with endometrial cancer compared with those without a family history.…”