Causal relationship between obesity, lifestyle factors and risk of benign prostatic hyperplasia: a univariable and multivariable Mendelian randomization study.

Li-Sha Luo, Yong-Bo Wang, Lan Yang, Yu-Qing Deng, Si-Yu Yan, Ping Chen, Xian-Tao Zeng

Journal: Journal of translational medicine 2022;20(1):495

PMID: 36309747

Plain Language Summary

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Benign prostatic hyperplasia (BPH) is a common benign disease in middle-aged and elderly men which is often underestimated and underdiagnosed. If patients are not treated in time, it may lead to serious complications, such as urinary retention, renal insufficiency and renal failure. The aim of this study was to evaluate the possible causal associations of abdominal obesity (measured as waist circumference), overall obesity (measured as body mass index), lifestyle factors (dietary habits, smoking, alcohol drinking, and sedentary behaviour) with risk of BPH. This study is a univariable and multivariable mendelian randomised study. Results show that genetic predisposition to higher waist circumference and sedentary behaviour are independently and causally associated with the risk of BPH. However, there isn’t conclusive evidence that genetic predisposition to relative carbohydrate, fat, protein, and sugar intake, smoking and alcohol drinking are causally associated with the risk of BPH. Authors conclude that further studies are needed to identify comprehensive risk factors on BPH and develop freely accessible prediction models for the BPH. These will help to identify individuals at particular risk and provide decision-making supports for individualised intervention.

Abstract

BACKGROUND

Obesity (waist circumference, body mass index (BMI)) and lifestyle factors (dietary habits, smoking, alcohol drinking, Sedentary behavior) have been associated with risk of benign prostatic hyperplasia (BPH) in observational studies, but whether these associations are causal is unclear.

METHODS

We performed a univariable and multivariable Mendelian randomization study to evaluate these associations. Genetic instruments associated with exposures at the genome-wide significance level (P < 5 × 10) were selected from corresponding genome-wide associations studies (n = 216,590 to 1,232,091 individuals). Summary-level data for BPH were obtained from the UK Biobank (14,126 cases and 169,762 non-cases) and FinnGen consortium (13,118 cases and 72,799 non-cases). Results from UK Biobank and FinnGen consortium were combined using fixed-effect meta-analysis.

RESULTS

The combined odds ratios (ORs) of BPH were 1.24 (95% confidence interval (CI), 1.07-1.43, P = 0.0045), 1.08 (95% CI 1.01-1.17, P = 0.0175), 0.94 (95% CI 0.67-1.30, P = 0.6891), 1.29 (95% CI 0.88-1.89, P = 0.1922), 1.23 (95% CI 0.85-1.78, P = 0.2623), and 1.04 (95% CI 0.76-1.42, P = 0.8165) for one standard deviation (SD) increase in waist circumference, BMI, and relative carbohydrate, fat, protein and sugar intake, 1.05 (95% CI 0.92-1.20, P = 0.4581) for one SD increase in prevalence of smoking initiation, 1.10 (95% CI 0.96-1.26, P = 0.1725) and 0.84 (95% CI 0.69-1.02, P = 0.0741) for one SD increase of log-transformed smoking per day and drinks per week, and 1.31 (95% CI 1.08-1.58, P = 0.0051) for one SD increase in sedentary behavior. Genetically predicted waist circumference (OR = 1.26, 95% CI 1.11-1.43, P = 0.0004) and sedentary behavior (OR = 1.14, 95% CI 1.05-1.23, P = 0.0021) were associated with BPH after the adjustment of BMI.

CONCLUSION

This study supports independent causal roles of high waist circumference, BMI and sedentary behavior in BPH.

© 2022. The Author(s).

Address: Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.; Division of Medical Affairs, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.; Department of Urology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, China.; Department of Urology, Zhongnan Hospital of Wuhan University, No. 169, Donghu Road, Wuchang District, Wuhan, 430071, China. [email protected].; Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. [email protected].; Department of Urology, Zhongnan Hospital of Wuhan University, No. 169, Donghu Road, Wuchang District, Wuhan, 430071, China. [email protected].
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