Smoking, alcohol consumption and cancer: A Mendelian randomisation study in UK Biobank and international genetic consortia participants

Susanna C Larsson*, Paul Carter, Siddhartha Kar, Mathew Vithayathil, Amy M Mason, Karl Michaëlsson, Stephen Burgess

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

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Abstract

Background
Observational studies have reported that smoking and alcohol consumption are associated with risk of certain cancers, but it remains unclear whether the associations are causal. This Mendelian randomisation study sought to investigate the causal associations of smoking and alcohol consumption with 19 site-specific cancers.

Methods and findings
We used summary-level data for genetic variants associated with smoking initiation (ever smoked regularly) and alcohol consumption, and the corresponding associations with lung, breast, ovarian, and prostate cancer from genome-wide association studies consortia. We additionally estimated genetic associations with 19 site-specific cancers among 367 643 European-descent individuals in UK Biobank who were 37-73 years of age when recruited from 2006 to 2010. Genetic predisposition to smoking initiation was associated with higher odds of lung cancer in the International Lung Cancer Consortium (OR 1.80; 95% CI 1.59-2.03; p=2.2610-21) and UK Biobank (odds ratio [OR] 2.26; 95% confidence interval [CI] 1.92-2.65; p=1.1710-22). We found strong or suggestive evidence that genetic predisposition to smoking was associated with higher odds of head and neck cancer (OR 1.40; 95% CI 1.13-1.74; p=0.002), oesophageal cancer (OR 1.83; 95% CI 1.34-2.49; p=1.3110-4), stomach cancer (OR 1.46; 95% CI 1.05-2.03; p=0.024), cervical cancer (OR 1.55; 95% CI 1.27-1.88; p=1.2410-5), and bladder cancer (OR 1.40 (95% CI 1.92-2.65; p=9.4010-5). In contrast, there was suggestive evidence of an inverse association between genetic predisposition to smoking and prostate cancer in the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome consortium (OR 0.90; 95% CI 0.83-0.98; p=0.011), and a similar estimate in UK Biobank (OR 0.90; 95% CI 0.80-1.02; p=0.104). We found limited evidence that genetically-predicted alcohol consumption was associated with any site-specific cancer or overall cancer (n=75 037 cases; OR 0.95; 95% CI 0.84-1.07; p=0.376). A positive association was observed for lung cancer in the International Lung Cancer Consortium, but not in UK Biobank.

Conclusions
This study confirms the well-established relationship between smoking and lung cancer, and indicates that smoking may also be a risk factor for cancer of the head and neck, oesophagus, stomach, cervix, and bladder. There was no evidence of a causal effect of alcohol consumption on overall cancer but an effect on any site-specific cancer cannot be precluded.
Original languageEnglish
Number of pages14
JournalPLoS Medicine
DOIs
Publication statusPublished - 23 Jul 2020

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