Associations between variants of the 8q24 chromosome and nine smoking-related cancer sites.
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.
Park
Sungshim Lani
SL
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.
Chang
Shen-Chih
SC
Cai
Lin
L
Cordon-Cardo
Carlos
C
Ding
Bao-Guo
BG
Greenland
Sander
S
Hussain
Shehnaz K
SK
Jiang
Qingwu
Q
Liu
Simin
S
Lu
Ming-Lan
ML
Mao
Jenny T
JT
Morgenstern
Hal
H
Mu
Li-Na
LN
Ng
Leslie J
LJ
Pantuck
Allan
A
Rao
Jianyu
J
Reuter
Victor E
VE
Tashkin
Donald P
DP
You
Nai-Chieh Y
NC
Yu
Can-Qing
CQ
Yu
Shun-Zhang
SZ
Zhao
Jin-Kou
JK
Belldegrun
Arie
A
Zhang
Zuo-Feng
ZF
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