The causal association between smoking, alcohol consumption and risk of bladder cancer: A univariable and multivariable Mendelian randomization study

• Published in: International journal of cancer Vol. 151; no. 12; pp. 2136 - 2143
• Main Authors: Xiong, Jie, Yang, Lan, Deng, Yu‐Qing, Yan, Si‐Yu, Gu, Jia‐Min, Li, Bing‐Hui, Zi, Hao, Ming, Dao‐Jing, Zeng, Xian‐Tao, Wang, Yong‐Bo
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 15-12-2022; Wiley Subscription Services, Inc
• Subjects: Alcohol; Alcohol Drinking - adverse effects; Alcohol Drinking - genetics; Alcohol use; Biobanks; Bladder cancer; Body mass index; Cancer; causal inference; Cigarettes; Consortia; Genome-Wide Association Study; Humans; Medical research; Mendelian randomization; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; Risk Factors; Single-nucleotide polymorphism; Smoking; Smoking - adverse effects; Smoking - genetics; Urinary Bladder Neoplasms - etiology; Urinary Bladder Neoplasms - genetics; United Kingdom > UK; alcohol; Mendelian randomization; causal inference; bladder cancer; smoking
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.34228

Smoking and alcohol consumption are associated with bladder cancer risk in observational studies. We conducted a two‐sample univariable and multivariable Mendelian randomization (MR) analysis to determine whether those associations are causal. We used 21, 126, 360, 39 single nucleotide polymorphisms (SNPs) as instrumental variables for number of cigarettes per day, lifetime smoking index, smoking initiation, and drinks per week, respectively. A total of 1115 cases with bladder cancer and 174 006 noncases from FinnGen consortium and 2883 cases with bladder cancer and 417 955 noncases from UK Biobank study were obtained. Genetic predisposition to cigarettes per day, lifetime smoking index and smoking initiation were positively associated with an increased risk of bladder cancer in both the FinnGen and UK Biobank consortium. The summary odds ratio (OR) of bladder cancer was 1.79 (95% confidence interval [CI], 1.31‐2.45; P = .0002), 2.38 (95% CI, 1.45‐3.88; P = .0005) and 1.91 (95% CI, 1.46‐2.50; P = 1.59 × 10−06) for one SD increase in the number of cigarettes per day, lifetime smoking index and smoking initiation, respectively. The genetically instrumented number of drinks per week was not associated with bladder cancer (OR = 0.69; 95% CI, 0.44‐1.10; P = .1237). Estimates were consistent in multivariable MR analyses by the adjustments of body mass index and education. Our study suggests a causal potential of the association of smoking but not alcohol consumption with bladder cancer according to current evidence.
What's new?
Smoking and alcohol consumption have been associated with bladder cancer risk in observational studies. However, the nature of these associations remains unclear. Here, the authors conducted a two‐sample univariable and multivariable Mendelian randomization analysis to explore the potential causal associations of genetic liability for smoking and alcohol consumption with bladder cancer risk. The results suggest that smoking is an important risk factor for bladder cancer. In contrast, there was no association between genetically‐predicted alcohol assumption and bladder cancer risk.