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 journalArticleAcademicpeer-review

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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 languageEnglish
Number of pages9
JournalBJU International
Publication statusE-pub ahead of print - 2 Sept 2022

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