Endometrial cancer risk factors by 2 main histologic subtypes

On the basis of clinical and pathologic criteria, endometrial carcinoma has been distinguished as Types I (mainly endometrioid) and II (nonendometrioid). Limited data suggest that these subtypes have different risk factor profiles. The authors prospectively evaluated risk factors for Types I (n = 1,312) and II (n = 138) incident endometrial carcinoma among 114,409 women in the National Institutes of Health (NIH)-AARP Diet and Health Study (1995-2006). For individual risk factors, relative risks were estimated with Cox regression by subtype, and P_{heterogeneity} was assessed in case-case comparisons with Type I as the referent. Stronger relations for Type I versus Type II tumors were seen for menopausal hormone therapy use (relative risk (RR) of 1.18 vs. 0.84; P_{heterogeneity} = 0.01) and body mass index of ≥30 vs. <30 kg/m² (RR of 2.93 vs. 1.83; P_{heterogeneity} = 0.001). Stronger relations for Type II versus Type I tumors were observed for being black versus white (RR of 2.18 vs. 0.66; P_{heterogeneity} = 0.0004) and having a family history of breast cancer (RR of 1.93 vs. 0.80; P _{heterogeneity} = 0.002). Other risk factor associations were similar by subtype. In conclusion, the authors noted different risk factor associations for Types I and II endometrial carcinomas, supporting the etiologic heterogeneity of these tumors. Because of the limited number of Type II cancers, additional evaluation of risk factors will benefit from consortial efforts.