title: Associations between variants of the 8q24 chromosome and nine smoking-related cancer sites.
abstract: 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 (ORadj), 1.69; 95% confidence interval (95% CI), 1.28-2.24], particularly in oropharynx (ORadj, 1.80; 95% CI, 1.30-2.49) and larynx (ORadj, 2.04; 95% CI, 1.12-3.72). We also observed a suggestive association between rs6983267 and liver cancer (ORadj, 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 (ORadj, 1.45; 95% CI, 1.05-2.00) and inversely associated with bladder cancer among ever-smokers (ORadj, 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.
authors.affiliation: 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, USA.
authors.forename: Sungshim Lani
authors.initials: SL
authors.lastname: Park
authors.forename: Shen-Chih
authors.initials: SC
authors.lastname: Chang
authors.forename: Lin
authors.initials: L
authors.lastname: Cai
authors.forename: Carlos
authors.initials: C
authors.lastname: Cordon-Cardo
authors.forename: Bao-Guo
authors.initials: BG
authors.lastname: Ding
authors.forename: Sander
authors.initials: S
authors.lastname: Greenland
authors.forename: Shehnaz K
authors.initials: SK
authors.lastname: Hussain
authors.forename: Qingwu
authors.initials: Q
authors.lastname: Jiang
authors.forename: Simin
authors.initials: S
authors.lastname: Liu
authors.forename: Ming-Lan
authors.initials: ML
authors.lastname: Lu
authors.forename: Jenny T
authors.initials: JT
authors.lastname: Mao
authors.forename: Hal
authors.initials: H
authors.lastname: Morgenstern
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Mu
authors.forename: Leslie J
authors.initials: LJ
authors.lastname: Ng
authors.forename: Allan
authors.initials: A
authors.lastname: Pantuck
authors.forename: Jianyu
authors.initials: J
authors.lastname: Rao
authors.forename: Victor E
authors.initials: VE
authors.lastname: Reuter
authors.forename: Donald P
authors.initials: DP
authors.lastname: Tashkin
authors.forename: Nai-Chieh Y
authors.initials: NC
authors.lastname: You
authors.forename: Can-Qing
authors.initials: CQ
authors.lastname: Yu
authors.forename: Shun-Zhang
authors.initials: SZ
authors.lastname: Yu
authors.forename: Jin-Kou
authors.initials: JK
authors.lastname: Zhao
authors.forename: Arie
authors.initials: A
authors.lastname: Belldegrun
authors.forename: Zuo-Feng
authors.initials: ZF
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008113:Liver Neoplasms / Q000208:ethnology / Q000235:genetics; D008175:Lung Neoplasms / Q000208:ethnology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000208:ethnology / Q000235:genetics*; D010039:Otorhinolaryngologic Neoplasms / Q000208:ethnology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D012907:Smoking / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000208:ethnology / Q000235:genetics