Objective Lynch Syndrome (LS), an inherited genetic syndrome, predisposes to cancers such as colorectal and endometrial. However, the risk for endometrial cancer (EC) in women not affected by LS, but with a family history of cancer, is currently unknown. We examined the association between a family history of cancer and the risk for EC in non-LS patients. Methods This population-based case-control study included 519 EC cases and 1015 age-matched controls and took place in Alberta, Canada between 2002 and 2006. Information about risk factors, including family history of cancer in first and second degree relatives, was ascertained via in-person interviews. Microsatellite instability (MSI) status of tumor tissue was assessed to determine involvement of DNA mismatch repair genes. Results A first or second degree family history of uterine cancer was modestly associated with the risk for overall EC [odds ratio (OR), 1.3; 95% confidence interval (CI), 0.9,1.9], and the risks were similar for MSI+ cancer (OR= 1.5, 95%CI=0.7, 3.3) and MSI- cancer (OR= 1.3, 95%CI=0.8, 2.4). Although consistent, these associations were modest and not significant. In contrast, the risk for MSI+ cancer was elevated with a reported family history of colorectal cancer (OR= 1.4, 95%CI=1.0, 2.2), but not for MSI- cancer. Conclusions A family history of uterine cancer may be modestly associated with EC risk in non-LS patients regardless of MSI status, suggesting that risk was not related to inherited defects in the MMR gene pathway. These results provide preliminary support for an EC-specific genetic syndrome.

There is a well-documented reduction in endometrial cancer risk with combined oral contraceptive (COC) use. COC use before the first full-term pregnancy may affect breast cancer risk for decades, but this relationship has not been investigated in endometrial cancer. We investigated the risk for endometrial cancer with COC use before the first full-term pregnancy. Cases (n ¼ 524) from a population-based cancer registry and age-matched controls (n ¼ 1,032) were recruited between 2002 and 2006 in Alberta, Canada. Participants completed an inperson interview and provided detailed information on exogenous hormone use and other risk factors. Risk reductions in endometrial cancer with COC use over the premenopausal years were consistent with the published literature. We also found evidence of a long-term, significant risk reduction in parous women with COC use before the first full-term pregnancy. Among parous women, 5 years of COC use before a first fullterm pregnancy was associated with a significant reduction in risk [adjusted OR, 0.42