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

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

1 Citation (Web of Science)

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: BC incidences (n=563) and non-BC controls (n=483,957) were identified in the UK Biobank, and adjusted Cox regression models were used. PRS was constructed based on 34 genetic variants associated with BC development, while a Healthy Lifestyle Score (HLS) was constructed based on 3 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-SD increment in the PRS and the HLS were observed, respectively. Additionally, a simultaneous increment of per 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 (HR 1.55, 95% CI 1.16-1.91, P for trend<0.001). Furthermore, Population-Attributable Fractions (PAF) analysis showed that 12-15% of the BC cases might have been prevented if individuals adhere to a healthy lifestyle.

CONCLUSION: This large-scale cohort study shows that a genetic predisposition combined with unhealth 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 the genetic risk.

Original language	English
Number of pages	9
Journal	BJU International
DOIs	https://doi.org/10.1111/bju.15880
Publication status	E-pub ahead of print - 2 Sept 2022

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10.1111/bju.15880Licence: CC BY-NC

Cite this

@article{1364dbed673d478cbd7362aa84f9c47c,

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: BC incidences (n=563) and non-BC controls (n=483,957) were identified in the UK Biobank, and adjusted Cox regression models were used. PRS was constructed based on 34 genetic variants associated with BC development, while a Healthy Lifestyle Score (HLS) was constructed based on 3 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-SD increment in the PRS and the HLS were observed, respectively. Additionally, a simultaneous increment of per 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 (HR 1.55, 95% CI 1.16-1.91, P for trend<0.001). Furthermore, Population-Attributable Fractions (PAF) analysis showed that 12-15% of the BC cases might have been prevented if individuals adhere to a healthy lifestyle.CONCLUSION: This large-scale cohort study shows that a genetic predisposition combined with unhealth 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 the genetic risk.",

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

year = "2022",

month = sep,

day = "2",

doi = "10.1111/bju.15880",

language = "English",

journal = "BJU International",

issn = "1464-4096",

publisher = "Wiley",

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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

PY - 2022/9/2

Y1 - 2022/9/2

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: BC incidences (n=563) and non-BC controls (n=483,957) were identified in the UK Biobank, and adjusted Cox regression models were used. PRS was constructed based on 34 genetic variants associated with BC development, while a Healthy Lifestyle Score (HLS) was constructed based on 3 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-SD increment in the PRS and the HLS were observed, respectively. Additionally, a simultaneous increment of per 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 (HR 1.55, 95% CI 1.16-1.91, P for trend<0.001). Furthermore, Population-Attributable Fractions (PAF) analysis showed that 12-15% of the BC cases might have been prevented if individuals adhere to a healthy lifestyle.CONCLUSION: This large-scale cohort study shows that a genetic predisposition combined with unhealth 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 the 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: BC incidences (n=563) and non-BC controls (n=483,957) were identified in the UK Biobank, and adjusted Cox regression models were used. PRS was constructed based on 34 genetic variants associated with BC development, while a Healthy Lifestyle Score (HLS) was constructed based on 3 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-SD increment in the PRS and the HLS were observed, respectively. Additionally, a simultaneous increment of per 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 (HR 1.55, 95% CI 1.16-1.91, P for trend<0.001). Furthermore, Population-Attributable Fractions (PAF) analysis showed that 12-15% of the BC cases might have been prevented if individuals adhere to a healthy lifestyle.CONCLUSION: This large-scale cohort study shows that a genetic predisposition combined with unhealth 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 the genetic risk.

U2 - 10.1111/bju.15880

DO - 10.1111/bju.15880

M3 - Article

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SN - 1464-4096

JO - BJU International

JF - BJU International

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