The effects of the interaction of genetic predisposition with lifestyle factors on bladder cancer risk

Evan Yi Wen Yu; Yu Xiang Liu; Ya Ting Chen; Qiu Yi Tang; Siamak Mehrkanoon; Shi Zhi Wang; Wen Chao Li; Maurice P. Zeegers; Anke Wesselius

doi:10.1111/bju.15880

The effects of the interaction of genetic predisposition with lifestyle factors on bladder cancer risk

Evan Yi Wen Yu^*, Yu Xiang Liu, Ya Ting Chen, Qiu Yi Tang, Siamak Mehrkanoon, Shi Zhi Wang, Wen Chao Li, Maurice P. Zeegers, Anke Wesselius

^*Corresponding author for this work

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Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Objectives: To investigate the association of polygenic risk score (PRS) and bladder cancer (BC) risk and whether this PRS can be offset by a healthy lifestyle. Methods: Individuals with BC (n = 563) and non-BC controls (n = 483 957) were identified in the UK Biobank, and adjusted Cox regression models were used. A PRS was constructed based on 34 genetic variants associated with BC development, while a healthy lifestyle score (HLS) was constructed based on three lifestyle factors (i.e., smoking, physical activity, and diet). Results: Overall, a negative interaction was observed between the PRS and the HLS (P = 0.02). A 7% higher and 28% lower BC risk per 1-standard deviation (SD) increment in PRS and HLS were observed, respectively. A simultaneous increment of 1 SD in both HLS and PRS was associated with a 6% lower BC risk. In addition, individuals with a high genetic risk and an unfavourable lifestyle showed an increased BC risk compared to individuals with low genetic risk and a favourable lifestyle (hazard ratio 1.55, 95% confidence interval 1.16–1.91; P for trend <0.001). Furthermore, population-attributable fraction (PAF) analysis showed that 12%–15% of the BC cases might have been prevented if individuals had adhered to a healthy lifestyle. Conclusion: This large-scale cohort study shows that a genetic predisposition combined with unhealthy behaviours have a joint negative effect on the risk of developing BC. Behavioural lifestyle changes should be encouraged for people through comprehensive, multifactorial approaches, although high-risk individuals may be selected based on genetic risk.

Original language	English
Pages (from-to)	443-451
Number of pages	9
Journal	BJU International
Volume	131
Issue number	4
DOIs	https://doi.org/10.1111/bju.15880
Publication status	Published - Apr 2023

Keywords

bladder cancer
cohort study
gene–environment interaction
healthy lifestyle
polygenic risk score

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BJU International - 2022 - YuFinal published version, 165 KBLicence: CC BY-NC

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@article{9a3d62588cc94912a1048d57afaf8862,

title = "The effects of the interaction of genetic predisposition with lifestyle factors on bladder cancer risk",

abstract = "Objectives: To investigate the association of polygenic risk score (PRS) and bladder cancer (BC) risk and whether this PRS can be offset by a healthy lifestyle. Methods: Individuals with BC (n = 563) and non-BC controls (n = 483 957) were identified in the UK Biobank, and adjusted Cox regression models were used. A PRS was constructed based on 34 genetic variants associated with BC development, while a healthy lifestyle score (HLS) was constructed based on three lifestyle factors (i.e., smoking, physical activity, and diet). Results: Overall, a negative interaction was observed between the PRS and the HLS (P = 0.02). A 7% higher and 28% lower BC risk per 1-standard deviation (SD) increment in PRS and HLS were observed, respectively. A simultaneous increment of 1 SD in both HLS and PRS was associated with a 6% lower BC risk. In addition, individuals with a high genetic risk and an unfavourable lifestyle showed an increased BC risk compared to individuals with low genetic risk and a favourable lifestyle (hazard ratio 1.55, 95% confidence interval 1.16–1.91; P for trend <0.001). Furthermore, population-attributable fraction (PAF) analysis showed that 12%–15% of the BC cases might have been prevented if individuals had adhered to a healthy lifestyle. Conclusion: This large-scale cohort study shows that a genetic predisposition combined with unhealthy behaviours have a joint negative effect on the risk of developing BC. Behavioural lifestyle changes should be encouraged for people through comprehensive, multifactorial approaches, although high-risk individuals may be selected based on genetic risk.",

keywords = "bladder cancer, cohort study, gene–environment interaction, healthy lifestyle, polygenic risk score",

author = "Yu, {Evan Yi Wen} and Liu, {Yu Xiang} and Chen, {Ya Ting} and Tang, {Qiu Yi} and Siamak Mehrkanoon and Wang, {Shi Zhi} and Li, {Wen Chao} and Zeegers, {Maurice P.} and Anke Wesselius",

note = "Funding Information: This research was conducted using the UK Biobank Resource under Application Number 55889. The work was partly supported by the Natural Science Foundation of Jiangsu Province (SBK2022041824), Fundamental Research Funds for the Central Universities of China (2242022R10062/3225002202A1), and Medical Foundation of Southeast University (4060692202/021). Publisher Copyright: {\textcopyright} 2022 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.",

year = "2023",

month = apr,

doi = "10.1111/bju.15880",

language = "English",

volume = "131",

pages = "443--451",

journal = "BJU International",

issn = "1464-4096",

publisher = "John Wiley and Sons Inc.",

number = "4",

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TY - JOUR

T1 - The effects of the interaction of genetic predisposition with lifestyle factors on bladder cancer risk

AU - Yu, Evan Yi Wen

AU - Liu, Yu Xiang

AU - Chen, Ya Ting

AU - Tang, Qiu Yi

AU - Mehrkanoon, Siamak

AU - Wang, Shi Zhi

AU - Li, Wen Chao

AU - Zeegers, Maurice P.

AU - Wesselius, Anke

N1 - Funding Information: This research was conducted using the UK Biobank Resource under Application Number 55889. The work was partly supported by the Natural Science Foundation of Jiangsu Province (SBK2022041824), Fundamental Research Funds for the Central Universities of China (2242022R10062/3225002202A1), and Medical Foundation of Southeast University (4060692202/021). Publisher Copyright: © 2022 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.

PY - 2023/4

Y1 - 2023/4

N2 - Objectives: To investigate the association of polygenic risk score (PRS) and bladder cancer (BC) risk and whether this PRS can be offset by a healthy lifestyle. Methods: Individuals with BC (n = 563) and non-BC controls (n = 483 957) were identified in the UK Biobank, and adjusted Cox regression models were used. A PRS was constructed based on 34 genetic variants associated with BC development, while a healthy lifestyle score (HLS) was constructed based on three lifestyle factors (i.e., smoking, physical activity, and diet). Results: Overall, a negative interaction was observed between the PRS and the HLS (P = 0.02). A 7% higher and 28% lower BC risk per 1-standard deviation (SD) increment in PRS and HLS were observed, respectively. A simultaneous increment of 1 SD in both HLS and PRS was associated with a 6% lower BC risk. In addition, individuals with a high genetic risk and an unfavourable lifestyle showed an increased BC risk compared to individuals with low genetic risk and a favourable lifestyle (hazard ratio 1.55, 95% confidence interval 1.16–1.91; P for trend <0.001). Furthermore, population-attributable fraction (PAF) analysis showed that 12%–15% of the BC cases might have been prevented if individuals had adhered to a healthy lifestyle. Conclusion: This large-scale cohort study shows that a genetic predisposition combined with unhealthy behaviours have a joint negative effect on the risk of developing BC. Behavioural lifestyle changes should be encouraged for people through comprehensive, multifactorial approaches, although high-risk individuals may be selected based on genetic risk.

AB - Objectives: To investigate the association of polygenic risk score (PRS) and bladder cancer (BC) risk and whether this PRS can be offset by a healthy lifestyle. Methods: Individuals with BC (n = 563) and non-BC controls (n = 483 957) were identified in the UK Biobank, and adjusted Cox regression models were used. A PRS was constructed based on 34 genetic variants associated with BC development, while a healthy lifestyle score (HLS) was constructed based on three lifestyle factors (i.e., smoking, physical activity, and diet). Results: Overall, a negative interaction was observed between the PRS and the HLS (P = 0.02). A 7% higher and 28% lower BC risk per 1-standard deviation (SD) increment in PRS and HLS were observed, respectively. A simultaneous increment of 1 SD in both HLS and PRS was associated with a 6% lower BC risk. In addition, individuals with a high genetic risk and an unfavourable lifestyle showed an increased BC risk compared to individuals with low genetic risk and a favourable lifestyle (hazard ratio 1.55, 95% confidence interval 1.16–1.91; P for trend <0.001). Furthermore, population-attributable fraction (PAF) analysis showed that 12%–15% of the BC cases might have been prevented if individuals had adhered to a healthy lifestyle. Conclusion: This large-scale cohort study shows that a genetic predisposition combined with unhealthy behaviours have a joint negative effect on the risk of developing BC. Behavioural lifestyle changes should be encouraged for people through comprehensive, multifactorial approaches, although high-risk individuals may be selected based on genetic risk.

KW - bladder cancer

KW - cohort study

KW - gene–environment interaction

KW - healthy lifestyle

KW - polygenic risk score

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U2 - 10.1111/bju.15880

DO - 10.1111/bju.15880

M3 - Article

C2 - 36053730

AN - SCOPUS:85138303799

SN - 1464-4096

VL - 131

SP - 443

EP - 451

JO - BJU International

JF - BJU International

IS - 4

ER -

The effects of the interaction of genetic predisposition with lifestyle factors on bladder cancer risk

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