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Body Mass Index, Hormone Replacement Therapy, and Endometrial Cancer Risk: A Meta-Analysis
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Abstract
Background: 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. Methods: 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. Results: 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/m2 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/m2, 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/m2, compared with never users at normal BMI. The association was not affected by menopausal status (P = 0.34) or histologic type (P = 0.26). Conclusions: HRT use modifies the BMI-endometrial cancer risk association. Impact: 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. Cancer Epidemiol Biomarkers Prev; 19(12); 3119–30. ©2010 AACR.
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“Established risk factors for development of EC include obesity and the presence of premalignant lesions associated with endometrial hyperplasia [75,76], with oestrogen exposure considered a key driver of both endometrial hyperplasia and Type I EC that make up 75% of EC cases [76].”
From Endometrial Intracrinology: Oestrogens, Androgens and Endometrial Disorders (2018) · cites this paper as [75]
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Einfluss endogener und exogener Hormone in der Peri- und Postmenopause auf das Krebsrisiko
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Metadata
- Authors
- Crosbie, E. J., Zwahlen, M., Kitchener, H. C., Egger, M., & Renehan, A. G.
- Affiliations
- University of Bern (CH)
- Venue
- Cancer Epidemiology, Biomarkers & Prevention
- Published
- 2010-12-01
- Volume
- 19
- Issue
- 12
- Pages
- 3119-3130
- ISSN
- 1055-9965 (ISSN-L)
- 1538-7755
- OpenAlex
- W2076975509
- Cited by
- 321
- References
- 85
- Citations by year
- 2026: 21 · 2025: 19 · 2024: 15 · 2023: 24 · 2022: 25 · 2021: 25 · 2020: 26 · 2019: 15 · 2018: 19 · 2017: 20 · 2016: 21 · 2015: 33 · 2014: 23 · 2013: 21 · 2012: 9
- FWCI
- 1.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Epidemiology Biomarkers & Prevention (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- BORIS (University Library Bern) (submittedVersion)
- Funders
- National Institute for Health and Care Research (CL-2007-06-005)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Risks and Factors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Health Sciences › Medicine › Obstetrics and Gynecology › Endometrial and Cervical Cancer Treatments
- Keywords
- body mass index, endometrial cancer, hormone replacement therapy, obesity, menopausal status, histological subtypes, cancer risk modification, dose-response relationship, postmenopausal women, endometrial hyperplasia, endometrial adenocarcinoma, endometrioid carcinoma, serous carcinoma
- MeSH terms
- Female, Humans, Risk Factors, Cohort Studies, Body Mass Index, Endometrial Neoplasms, Hormone Replacement Therapy
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