Interactions of obesity, body shape, diabetes and sex steroids with respect to prostate cancer risk in the UK Biobank cohort

Q: How were diabetes, obesity, body shape, and sex hormones analyzed for prostate cancer risk?

The study used multivariable Cox proportional hazards models in UK Biobank men to assess independent associations and to test multiplicative and additive interactions.

Q: What did the results show about the combined effect of obesity and diabetes?

Diabetes and BMI showed synergistic inverse associations with prostate cancer risk, with significant interaction measures reported for the co-occurrence of diabetes and obesity.

Q: Did ABSI and sex steroid measures modify the associations with prostate cancer risk?

Yes. The inverse associations related to obesity and diabetes were attenuated for higher ABSI, and associations also differed across testosterone and oestradiol categories and with SHBG and HI.

Sep 21, 2026

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Background: Obesity and diabetes are linked to lower low-grade prostate cancer risk and influence steroid hormone synthesis, yet it remains unclear whether they modify each other’s effects on prostate cancer risk. Methods: Independent associations of diabetes, BMI, ABSI, hip index, testosterone, SHBG, and oestradiol were assessed using multivariable Cox models in UK Biobank men. Multiplicative and additive interactions were evaluated with obesity (BMI ≥30) and diabetes. Results: Over 10.3 years, 9417 incident cases occurred among 195,813 men, showing synergistic inverse associations; effects varied by ABSI and hormone measures.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages16

Reading Time40 min

AccessFree to download

Abstract

Background

Methods

Results

Conclusions

Introduction

Obesity, diabetes, and low-grade prostate cancer

Androgen and oestrogen involvement

Abdominal and hip measures (WC, BMI, ABSI, HI)

DOI: 10. 1002/cam4 .6918 RESEAR CH ARTICLE Interactions of obesity, body shape, diabetes and sex steroids with respect to prostate cancer risk in the UK Biobank cohort Sofia Christakoudi1,2 | Konstantinos K. Tsilidis1,3 | Evangelos Evangelou1,3 | Elio Riboli1 1Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK 2Department of Inflammation Biology, School of Immunology and Microbial Sciences, King's College London, London, UK 3Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece Correspondence Sofia Christakoudi, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St Mary's Campus, London, W2 1PG, UK. Email: [s.christakoudi@imperial.ac.uk](s.christakoudi@imperial.ac.uk) Funding information NIHR Imperial Biomedical Research Centre Abstract Background: Obesity and diabetes are associated inversely with low-grade prostate cancer risk and affect steroid hormone synthesis but whether they modify each other's impact on prostate cancer risk remains unknown. Methods: We examined the independent associations of diabetes, body mass index (BMI), ‘a body shape index’(ABSI), hip index (HI), circulating testosterone, sex hormone binding globulin (SHBG) (per one standard deviation increase) and oestradiol ≥175 pmol/L with total prostate cancer risk using multivariable Cox proportional hazards models for UK Biobank men. We evaluated multiplicative interactions (pMI) and additive interactions (relative excess risk from interaction (pRERI), attributable proportion (pAR), synergy index (pSI)) with obese (BMI ≥30 kg/m2) and diabetes. Results: During a mean follow-up of 10.3 years, 9417 incident prostate cancers were diagnosed in 195,813 men. Diabetes and BMI were associated more strongly inversely with prostate cancer risk when occurring together (pMI = 0.0003, pRERI = 0.032, pAP = 0.020, pSI = 0.002) . ABSI was associated positively in obesemen (HR = 1.081; 95% CI = 1.030–1. 135) and men with diabetes (HR = 1. 114; 95% CI = 1.021–1.216) . The inverse associations with obesity and diabetes were attenuated for high-ABSI ≥79.8 (pMI = 0.022, pRERI = 0.008, pAP = 0.005, pSI <0.0001 obesity; pMI = 0.017, pRERI = 0.047, pAP = 0.025, pSI = 0.0005 diabetes) . HI was associated inversely in men overall (HR = 0.967; 95% CI = 0.947–0.988) . Free testosterone (FT) was associated most strongly positively in normal weight men (HR = 1.098; 95% CI = 1.045–1. 153) and men with diabetes (HR = 1. 189; 95% CI = 1.081–1.308). Oestradiol was associated inversely in obese men (HR = 0.805; 95% CI = 0.682–0.951) . The inverse association with obesity was stronger for high-FT ≥243 pmol/L (pRERI = 0.040, pAP = 0.031, pSI = 0.002) and high-oestradiol (pRERI = 0.030, pAP = 0.012, pSI <0.0001). The inverse association with diabetes was attenuated for high-FT (pMI = 0.008, pRERI = 0.015, pAP = 0.009, pSI = 0.0006) . SHBG This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. Cancer Medicine. 2024;13:e6918 . [https://doi.org/10.1002/cam4.6918](https://doi.org/10.1002/cam4.6918) [wileyonlinelibrary.com/journal/cam4](wileyonlinelibrary.com/journal/cam4) 1 of 16 was associated inversely in men overall (HR = 0.918; 95% CI = 0.895–0.941), more strongly for high-HI ≥49.1 (pMI = 0.024) . Conclusions: Obesity and diabetes showed synergistic inverse associations with prostate cancer risk, likely involving testosterone reduction for diabetes andoestrogen generation for obesity, which were attenuated for high-ABSI. HI and SHBG showed synergistic inverse associations with prostate cancer risk. KEYWORDS cancer prevention, cancer risk factors, epidemiology, prostate cancer 1 | INTROD

FAQs

How were diabetes, obesity, body shape, and sex hormones analyzed for prostate cancer risk?

The study used multivariable Cox proportional hazards models in UK Biobank men to assess independent associations and to test multiplicative and additive interactions.

What did the results show about the combined effect of obesity and diabetes?

Diabetes and BMI showed synergistic inverse associations with prostate cancer risk, with significant interaction measures reported for the co-occurrence of diabetes and obesity.

Did ABSI and sex steroid measures modify the associations with prostate cancer risk?

Yes. The inverse associations related to obesity and diabetes were attenuated for higher ABSI, and associations also differed across testosterone and oestradiol categories and with SHBG and HI.

Sep 21, 2026

Uploaded by Anda