Endometrial Cancer Risk Increased With Family History
Women’s risk for endometrial cancer is increased by 82% if they have a mother, sister, or daughter with endometrial cancer, according to a meta-analysis published online December 5 in Obstetrics & Gynecology. Their risk is also increased by 17% if a close relative has colorectal cancer.
Known risk factors for endometrial cancer include age, estrogen use, early menarche, late menopause, obesity, and diabetes, but previous studies had not settled the question of whether family history for endometrial or other cancers should be considered to raise women’s risk.
Aung Ko Win, PhD, from the Centre for Epidemiology and Biostatistics at the University of Melbourne in Australia, and colleagues reviewed 10 case-control studies that included a total of 3871 patients with endometrial cancer and 49,475 female control patients, as well as six cohort studies that included 33,510 women.
The authors found that women with a first-degree relative with endometrial cancer had a relative risk for endometrial cancer of 1.82 (95% confidence interval [CI], 1.65 – 1.98). By age 70 years, women with this family history had a 3.1% risk of developing endometrial cancer (95% CI, 2.8% – 3.4%) compared with a 1.7% risk for women without such a history. This increased risk was not dependent on age (comparing age 55 years or older with younger than 55 years; P = .15), premenopausal or postmenopausal status (P = .45), or whether the affected relative was a mother vs a sister (P = .75).
There was no evidence of association between endometrial cancer and first-degree family history of breast cancer (relative risk [RR], 0.96; 95% CI, 0.88 – 1.04), ovarian cancer (RR, 1.13; 95% CI, 0.85 – 1.41), or cervical cancer (RR, 1.19; 95% CI, 0.83 – 1.55). However, a first-degree family history of colon cancer was linked to a higher risk (RR, 1.17; 95% CI, 1.03 – 1.31).
The authors were unable to test whether risk is increased when a family history includes many affected relatives; whether risk is higher if the affected relative is a sister, rather than a mother; and whether the relative’s age at diagnosis increases a woman’s risk. Because relatives’ cancer diagnoses were usually unverified, the authors excluded second- and third-degree relatives, such as cousins and grandparents, because patients’ recall of family history is less accurate for these relatives.
Lynch syndrome, a germline mutation in DNA mismatch repair genes, is known to be a genetic risk factor for endometrial cancer, but three of the studies found the family history association in families did not have Lynch syndrome. The authors write that these findings, and the association of endometrial cancer with early-onset colorectal cancer, suggest there may be genes other than the ones involved in Lynch syndrome that can predispose women to endometrial cancer.
Obstet Gynecol. Published online December 5, 2014.