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Associations between Variants of the 8q24 Chromosome and Nine Smoking-Related Cancer Sites

¹ Department of Epidemiology, University of California at Los Angeles School of Public Health; ² Department of Statistics and ³ Jonsson Comprehensive Cancer Center, University of California at Los Angeles; ⁴ Division of Pulmonary and Critical Care Medicine; ⁵ Department of Urology; ⁶ Departments of Pathology and Laboratory Medicine, University of California at Los Angeles David Geffen School of Medicine, Los Angeles, California; ⁷ Department of Epidemiology, School of Public Health, Fujian Medical University, Fuzhou, People's Republic of China; ⁸ Herbert Irwing Comprehensive Cancer Center, Columbia University; ⁹ Departments of Pathology and Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York; ¹⁰ Taixing City Center for Disease Prevention and Control, Taixing City, Jiangsu, People's Republic of China; ¹¹ Fudan University School of Public Health, Shanghai, People's Republic of China; ¹² Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, Michigan; ¹³ Department of Social and Preventive Medicine, State University of New York, Buffalo, New York; ¹⁴ School of Public Health, Peking University, Beijing, People's Republic of China; and ¹⁵ Gates Foundation Beijing Office, Beijing, People's Republic of China

Requests for reprints: Zuo-Feng Zhang, Department of Epidemiology, University of California at Los Angeles School of Public Health, 71-225 CHS, Box 951772, 650 Charles E. Young Drive South, Los Angeles, CA 90095-1772. Phone: 310-825-8418; Fax: 310-206-6039. E-mail: zfzhang{at}ucla.edu

Recent genome-wide association studies identified key single nucleotide polymorphisms (SNPs) in the 8q24 region to be associated with prostate cancer. 8q24 SNPs have also been associated with colorectal cancer, suggesting that this region may not be specifically associated to just prostate cancer. To date, the association between these polymorphisms and tobacco smoking-related cancer sites remains unknown. Using epidemiologic data and biological samples previously collected in three case-control studies from U.S. and Chinese populations, we selected and genotyped one SNP from each of the three previously determined "regions" within the 8q24 loci, rs1447295 (region 1), rs16901979 (region 2), and rs6983267 (region 3), and examined their association with cancers of the lung, oropharynx, nasopharynx, larynx, esophagus, stomach, liver, bladder, and kidney. We observed noteworthy associations between rs6983267 and upper aerodigestive tract cancers [adjusted odds ratio (OR_adj), 1.69; 95% confidence interval (95% CI), 1.28-2.24], particularly in oropharynx (OR_adj, 1.80; 95% CI, 1.30-2.49) and larynx (OR_adj, 2.04; 95% CI, 1.12-3.72). We also observed a suggestive association between rs6983267 and liver cancer (OR_adj, 1.51; 95% CI, 0.99-2.31). When we stratified our analysis by smoking status, rs6983267 was positively associated with lung cancer among ever-smokers (OR_adj, 1.45; 95% CI, 1.05-2.00) and inversely associated with bladder cancer among ever-smokers (OR_adj, 0.35; 95% CI, 0.14-0.83). Associations were observed between rs16901979 and upper aerodigestive tract cancer among never-smokers and between rs1447295 and liver cancer among ever-smokers. Our results suggest variants of the 8q24 chromosome may play an important role in smoking-related cancer development. Functional and large epidemiologic studies should be conducted to further investigate the association of 8q24 SNPs with smoking-related cancers. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3193–202)

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