Smoking, alcohol consumption, and cancer: A mendelian randomisation study in UK Biobank and international genetic consortia participants
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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:
https://doi.org/10.1371/journal.pmed.1003178
Souhrn
Background
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.
Conclusions
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
Zdroje
1. Collaborators GBDA. Alcohol use and burden for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2018;392: 1015–35. doi: 10.1016/S0140-6736(18)31310-2 30146330
2. Inoue-Choi M, Liao LM, Reyes-Guzman C, Hartge P, Caporaso N, Freedman ND. Association of long-term, low-intensity smoking with all-cause and cause-specific mortality in the National Institutes of Health-AARP Diet and Health Study. JAMA Intern Med. 2017;177: 87–95. doi: 10.1001/jamainternmed.2016.7511 27918784
3. World Health Organization. WHO global report on mortality attributable to tobacco. Geneva: World Health Organization, 2012. Available from: https://apps.who.int/iris/handle/10665/44815.
4. Gandini S, Botteri E, Iodice S, Boniol M, Lowenfels AB, Maisonneuve P, et al. Tobacco smoking and cancer: a meta-analysis. Int J Cancer. 2008;122: 155–64. doi: 10.1002/ijc.23033 17893872
5. Pirie K, Peto R, Reeves GK, Green J, Beral V, Million Women Study C. The 21st century hazards of smoking and benefits of stopping: a prospective study of one million women in the UK. Lancet. 2013;381: 133–41. doi: 10.1016/S0140-6736(12)61720-6 23107252
6. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Tobacco smoke and involuntary smoking. IARC Monogr Eval Carcinog Risks Hum 2004;83: 1–1438. 15285078
7. Secretan B, Straif K, Baan R, Grosse Y, El Ghissassi F, Bouvard V, et al. A review of human carcinogens—Part E: tobacco, areca nut, alcohol, coal smoke, and salted fish. Lancet Oncol. 2009;10: 1033–4. doi: 10.1016/s1470-2045(09)70326-2 19891056
8. McGee EE, Jackson SS, Petrick JL, Van Dyke AL, Adami HO, Albanes D, et al. Smoking, alcohol, and biliary tract cancer risk: a Pooling Project of 26 prospective studies. J Natl Cancer Inst. 2020;111: 1263–78. doi: 10.1093/jnci/djz103 31127946
9. Allen NE, Beral V, Casabonne D, Kan SW, Reeves GK, Brown A, et al. Moderate alcohol intake and cancer incidence in women. J Natl Cancer Inst. 2009;101: 296–305. doi: 10.1093/jnci/djn514 19244173
10. McNabb S, Harrison TA, Albanes D, Berndt SI, Brenner H, Caan BJ, et al. Meta-analysis of 16 studies of the association of alcohol with colorectal cancer. Int J Cancer. 2020;146: 861–73. doi: 10.1002/ijc.32377 31037736
11. Lee JE, Hunter DJ, Spiegelman D, Adami HO, Albanes D, Bernstein L, et al. Alcohol intake and renal cell cancer in a pooled analysis of 12 prospective studies. J Natl Cancer Inst. 2007;99: 801–10. doi: 10.1093/jnci/djk181 17505075
12. Bagnardi V, Rota M, Botteri E, Tramacere I, Islami F, Fedirko V, et al. Alcohol consumption and site-specific cancer risk: a comprehensive dose-response meta-analysis. Br J Cancer. 2015;112: 580–93. doi: 10.1038/bjc.2014.579 25422909
13. Jung S, Wang M, Anderson K, Baglietto L, Bergkvist L, Bernstein L, et al. Alcohol consumption and breast cancer risk by estrogen receptor status: in a pooled analysis of 20 studies. Int J Epidemiol. 2016;45: 916–28. doi: 10.1093/ije/dyv156 26320033
14. Bagnardi V, Rota M, Botteri E, Tramacere I, Islami F, Fedirko V, et al. Light alcohol drinking and cancer: a meta-analysis. Ann Oncol. 2013;24: 301–8. doi: 10.1093/annonc/mds337 22910838
15. Liu M, Jiang Y, Wedow R, Li Y, Brazel DM, Chen F, et al. Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use. Nat Genet. 2019;51: 237–44. doi: 10.1038/s41588-018-0307-5 30643251
16. Wang Y, McKay JD, Rafnar T, Wang Z, Timofeeva MN, Broderick P, et al. Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer. Nat Genet. 2014;46: 736–41. doi: 10.1038/ng.3002 24880342
17. Michailidou K, Lindstrom S, Dennis J, Beesley J, Hui S, Kar S, et al. Association analysis identifies 65 new breast cancer risk loci. Nature. 2017;551: 92–4. doi: 10.1038/nature24284 29059683
18. Phelan CM, Kuchenbaecker KB, Tyrer JP, Kar SP, Lawrenson K, Winham SJ, et al. Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer. Nat Genet. 2017;49: 680–91. doi: 10.1038/ng.3826 28346442
19. Schumacher FR, Al Olama AA, Berndt SI, Benlloch S, Ahmed M, Saunders EJ, et al. Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci. Nat Genet. 2018;50: 928–36. doi: 10.1038/s41588-018-0142-8 29892016
20. Hemani G, Zheng J, Elsworth B, Wade KH, Haberland V, Baird D, et al. The MR-Base platform supports systematic causal inference across the human phenome. Elife. 2018;7: pii: e34408. doi: 10.7554/eLife.34408 29846171
21. Sudlow C, Gallacher J, Allen N, Beral V, Burton P, Danesh J, et al. UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med. 2015;12: e1001779. doi: 10.1371/journal.pmed.1001779 25826379
22. Machiela MJ, Chanock SJ. LDlink: a web-based application for exploring population-specific haplotype structure and linking correlated alleles of possible functional variants. Bioinformatics. 2015;31: 3555–7. doi: 10.1093/bioinformatics/btv402 26139635
23. Burgess S, Bowden J, Fall T, Ingelsson E, Thompson SG. Sensitivity analyses for robust causal inference from Mendelian randomization analyses with multiple genetic variants. Epidemiology. 2017;28: 30–42. doi: 10.1097/EDE.0000000000000559 27749700
24. Burgess S, Foley CN, Allara E, Staley JR, Howson JMM. A robust and efficient method for Mendelian randomization with hundreds of genetic variants. Nat Commun. 2020;11: 376. doi: 10.1038/s41467-019-14156-4 31953392
25. Verbanck M, Chen CY, Neale B, Do R. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nat Genet. 2018;50: 693–8. doi: 10.1038/s41588-018-0099-7 29686387
26. Spiller W, Davies NM, Palmer TM. Software application profile: mrrobust—a tool for performing two-sample summary Mendelian randomization analyses Int J Epidemiol. 2019;48: 684–90. doi: 10.1093/ije/dyy195
27. Yavorska OO, Burgess S. MendelianRandomization: an R package for performing Mendelian randomization analyses using summarized data. Int J Epidemiol. 2017;46: 1734–9. doi: 10.1093/ije/dyx034 28398548
28. Burgess S. Sample size and power calculations in Mendelian randomization with a single instrumental variable and a binary outcome. Int J Epidemiol. 2014;43: 922–9. doi: 10.1093/ije/dyu005 24608958
29. Fircanis S, Merriam P, Khan N, Castillo JJ. The relation between cigarette smoking and risk of acute myeloid leukemia: an updated meta-analysis of epidemiological studies. Am J Hematol. 2014;89: E125–32. doi: 10.1002/ajh.23744 24753145
30. Huncharek M, Haddock KS, Reid R, Kupelnick B. Smoking as a risk factor for prostate cancer: a meta-analysis of 24 prospective cohort studies. Am J Public Health. 2010;100: 693–701. doi: 10.2105/AJPH.2008.150508 19608952
31. Rohrmann S, Linseisen J, Allen N, Bueno-de-Mesquita HB, Johnsen NF, Tjonneland A, et al. Smoking and the risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition. Br J Cancer. 2013;108: 708–14. doi: 10.1038/bjc.2012.520 23169298
32. Watters JL, Park Y, Hollenbeck A, Schatzkin A, Albanes D. Cigarette smoking and prostate cancer in a prospective US cohort study. Cancer Epidemiol Biomarkers Prev. 2009;18: 2427–35. doi: 10.1158/1055-9965.EPI-09-0252 19706848
33. Brien SE, Ronksley PE, Turner BJ, Mukamal KJ, Ghali WA. Effect of alcohol consumption on biological markers associated with risk of coronary heart disease: systematic review and meta-analysis of interventional studies. BMJ. 2011;342: d636. doi: 10.1136/bmj.d636 21343206
34. Udenigwe CC, Ramprasath VR, Aluko RE, Jones PJ. Potential of resveratrol in anticancer and anti-inflammatory therapy. Nutr Rev. 2008;66: 445–54. doi: 10.1111/j.1753-4887.2008.00076.x 18667005
35. Fernandez-Panchon MS, Villano D, Troncoso AM, Garcia-Parrilla MC. Antioxidant activity of phenolic compounds: from in vitro results to in vivo evidence. Crit Rev Food Sci Nutr. 2008;48: 649–71. doi: 10.1080/10408390701761845 18663616
36. Boccia S, Hashibe M, Galli P, De Feo E, Asakage T, Hashimoto T, et al. Aldehyde dehydrogenase 2 and head and neck cancer: a meta-analysis implementing a Mendelian randomization approach. Cancer Epidemiol Biomarkers Prev. 2009;18: 248–54. doi: 10.1158/1055-9965.EPI-08-0462 19124505
37. Lewis SJ, Smith GD. Alcohol, ALDH2, and esophageal cancer: a meta-analysis which illustrates the potentials and limitations of a Mendelian randomization approach. Cancer Epidemiol Biomarkers Prev. 2005;14: 1967–71. doi: 10.1158/1055-9965.EPI-05-0196 16103445
38. Wang J, Wang H, Chen Y, Hao P, Zhang Y. Alcohol ingestion and colorectal neoplasia: a meta-analysis based on a Mendelian randomization approach. Colorectal Dis. 2011;13: e71–8. doi: 10.1111/j.1463-1318.2010.02530.x 21114754
39. Rota M, Porta L, Pelucchi C, Negri E, Bagnardi V, Bellocco R, et al. Alcohol drinking and risk of leukemia-a systematic review and meta-analysis of the dose-risk relation. Cancer Epidemiol. 2014;38: 339–45. doi: 10.1016/j.canep.2014.06.001 24986108
40. Brunner C, Davies NM, Martin RM, Eeles R, Easton D, Kote-Jarai Z, et al. Alcohol consumption and prostate cancer incidence and progression: A Mendelian randomisation study. Int J Cancer. 2017;140: 75–85. doi: 10.1002/ijc.30436 27643404
41. Burgess S, Davies NM, Thompson SG. Bias due to participant overlap in two-sample Mendelian randomization. Genet Epidemiol. 2016;40: 597–608. doi: 10.1002/gepi.21998 27625185
42. Palmer TM, Sterne JA, Harbord RM, Lawlor DA, Sheehan NA, Meng S, et al. Instrumental variable estimation of causal risk ratios and causal odds ratios in Mendelian randomization analyses. Am J Epidemiol. 2011;173: 1392–403. doi: 10.1093/aje/kwr026 21555716
43. Vansteelandt S, Bowden J, Babanezhad M, Goetghebeur E. On instrumental variables estimation of causal odds ratios. Stat Sci. 2011;26: 403–22.
44. Larsson SC, Mason AM, Back M, Klarin D, Damrauer SM, Million Veteran P, et al. Genetic predisposition to smoking in relation to 14 cardiovascular diseases. Eur Heart J. 2020. doi: 10.1093/eurheartj/ehaa193 32300774
45. Larsson SC, Burgess S, Michaëlsson K. Smoking and stroke: a Mendelian randomization study. Ann Neurol. 2019;86: 468–71. doi: 10.1002/ana.25534 31237718
46. Yuan S, Larsson SC. A causal relationship between cigarette smoking and type 2 diabetes mellitus: A Mendelian randomization study. Sci Rep. 2019;9: 19342. doi: 10.1038/s41598-019-56014-9 31852999
47. Yuan S, Michaelsson K, Wan Z, Larsson SC. Associations of Smoking and Alcohol and Coffee Intake with Fracture and Bone Mineral Density: A Mendelian Randomization Study. Calcif Tissue Int. 2019;105: 582–8. doi: 10.1007/s00223-019-00606-0 31482193
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