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

Autoři: Susanna C. Larsson aff001;  Paul Carter aff003;  Siddhartha Kar aff004;  Mathew Vithayathil aff005;  Amy M. Mason aff006;  Karl Michaëlsson aff001;  Stephen Burgess aff003
Působiště autorů: Department of Surgical Sciences, Uppsala University, Uppsala, Sweden aff001;  Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden aff002;  Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom aff003;  MRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, United Kingdom aff004;  MRC Cancer Unit, University of Cambridge, Cambridge, United Kingdom aff005;  British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom aff006;  National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge and Cambridge University Hospitals, Cambridge, United Kingdom aff007;  MRC Biostatistics Unit, University of Cambridge, Cambridge, United Kingdom aff008
Vyšlo v časopise: Smoking, alcohol consumption, and cancer: A mendelian randomisation study in UK Biobank and international genetic consortia participants. PLoS Med 17(7): e32767. doi:10.1371/journal.pmed.1003178
Kategorie: Research Article
doi: 10.1371/journal.pmed.1003178



Smoking is a well-established cause of lung cancer and there is strong evidence that smoking also increases the risk of several other cancers. Alcohol consumption has been inconsistently associated with cancer risk in observational studies. This mendelian randomisation (MR) study sought to investigate associations in support of a causal relationship between smoking and alcohol consumption and 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, including participants of European ancestry. We additionally estimated genetic associations with 19 site-specific cancers among 367,643 individuals of European descent in UK Biobank who were 37 to 73 years of age when recruited from 2006 to 2010. Associations were considered statistically significant at a Bonferroni corrected p-value below 0.0013. Genetic predisposition to smoking initiation was associated with statistically significant higher odds of lung cancer in the International Lung Cancer Consortium (odds ratio [OR] 1.80; 95% confidence interval [CI] 1.59–2.03; p = 2.26 × 10−21) and UK Biobank (OR 2.26; 95% CI 1.92–2.65; p = 1.17 × 10−22). Additionally, genetic predisposition to smoking was associated with statistically significant higher odds of cancer of the oesophagus (OR 1.83; 95% CI 1.34–2.49; p = 1.31 × 10−4), cervix (OR 1.55; 95% CI 1.27–1.88; p = 1.24 × 10−5), and bladder (OR 1.40; 95% CI 1.92–2.65; p = 9.40 × 10−5) and with statistically nonsignificant higher odds of head and neck (OR 1.40; 95% CI 1.13–1.74; p = 0.002) and stomach cancer (OR 1.46; 95% CI 1.05–2.03; p = 0.024). In contrast, there was 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 in UK Biobank (OR 0.90; 95% CI 0.80–1.02; p = 0.104), but the associations did not reach statistical significance. We found no statistically significant association between genetically predicted alcohol consumption and overall cancer (n = 75,037 cases; OR 0.95; 95% CI 0.84–1.07; p = 0.376). Genetically predicted alcohol consumption was statistically significantly associated with lung cancer in the International Lung Cancer Consortium (OR 1.94; 95% CI 1.41–2.68; p = 4.68 × 10−5) but not in UK Biobank (OR 1.12; 95% CI 0.65–1.93; p = 0.686). There was no statistically significant association between alcohol consumption and any other site-specific cancer. The main limitation of this study is that precision was low in some analyses, particularly for analyses of alcohol consumption and site-specific cancers.


Our findings support the well-established relationship between smoking and lung cancer and suggest that smoking may also be a risk factor for cancer of the head and neck, oesophagus, stomach, cervix, and bladder. We found no evidence supporting a relationship between alcohol consumption and overall or site-specific cancer risk.

Klíčová slova:

Alcohol consumption – Consortia – Genetic predisposition – Head – Lung and intrathoracic tumors – Observational studies – Prostate cancer – Smoking habits


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