Body mass index, hormone replacement therapy, and endometrial cancer risk: a meta-analysis

Body mass index (BMI) is a risk factor for endometrial cancer. We quantified the risk and investigated whether the association differed by use of hormone replacement therapy (HRT), menopausal status, and histologic type.

We searched MEDLINE and EMBASE (1966 to December 2009) to identify prospective studies of BMI and incident endometrial cancer. We did random-effects meta-analyses, meta-regressions, and generalized least square regressions for trend estimations assuming linear, and piecewise linear, relationships.

Twenty-four studies (17,710 cases) were analyzed; 9 studies contributed to analyses by HRT, menopausal status, or histologic type, all published since 2003. In the linear model, the overall risk ratio (RR) per 5 kg/m(2) increase in BMI was 1.60 (95% CI, 1.52-1.68), P < 0.0001. In the piecewise model, RRs compared with a normal BMI were 1.22 (1.19-1.24), 2.09 (1.94-2.26), 4.36 (3.75-5.10), and 9.11 (7.26-11.51) for BMIs of 27, 32, 37, and 42 kg/m(2), respectively. The association was stronger in never HRT users than in ever users: RRs were 1.90 (1.57-2.31) and 1.18 (95% CI, 1.06-1.31) with P for interaction = 0.003. In the piecewise model, the RR in never users was 20.70 (8.28-51.84) at BMI 42 kg/m(2), compared with never users at normal BMI. The association was not affected by menopausal status (P = 0.34) or histologic type (P = 0.26).

HRT use modifies the BMI-endometrial cancer risk association.

These findings support the hypothesis that hyperestrogenia is an important mechanism underlying the BMI-endometrial cancer association, whilst the presence of residual risk in HRT users points to the role of additional systems.