Single nucleotide polymorphisms of 8 inflammation-related genes and their associations with smoking-related cancers.
Tobacco smoke and its metabolites are carcinogens that increase tissue oxidative stress and induce target tissue inflammation. We hypothesized that genetic variation of inflammatory pathway genes plays a role in tobacco-related carcinogenesis and is modified by tobacco smoking. We evaluated the association of 12 single nucleotide polymorphisms of 8 inflammation-related genes with tobacco-related cancers (lung, oropharynx, larynx, esophagus, stomach, liver, bladder, and kidney) using 3 case-control studies from: Los Angeles (population-based; 611 lung and 553 upper aero-digestive tract cancer cases and 1,040 controls), Taixing, China (population-based; 218 esophagus, 206 stomach, 204 liver cancer cases, and 415 controls), and Memorial Sloan-Kettering Cancer Center (hospital-based; 227 bladder cancer cases and 211 controls). After adjusting for age, education, ethnicity, gender, and tobacco smoking, IL10 rs1800871 was inversely associated with oropharyngeal cancer (CT+TT vs. CC adjusted odds ratio [aOR]: 0.69, 95% confidence interval [CI]: 0.50-0.95), and was positively associated with lung cancer among never smokers (TT vs. CT+CC aOR: 2.5, 95% CI: 1.3-5.1) and inversely with oropharyngeal cancer among ever smokers (CT+TT vs. CC aOR: 0.63, 95% CI: 0.41-0.95). Among all pooled never smokers (588 cases and 816 controls), TNF rs1799964 was inversely associated with smoking-related cancer (CC vs. CT+TT aOR: 0.36, 95% CI: 0.17-0.77). Bayesian correction for multiple comparisons suggests that chance is unlikely to explain our findings (although epigenetic mechanisms may be in effect), which support our hypotheses, suggesting that IL10 rs1800871 is a susceptibility marker for oropharyngeal and lung cancers, and that TNF rs1799964 is associated with smoking-related cancers among never smokers.
Oh
Sam S
SS
Department of Epidemiology, University of California, Los Angeles (UCLA) School of Public Health, Los Angeles, CA, USA.
Chang
Shen-Chih
SC
Cai
Lin
L
Cordon-Cardo
Carlos
C
Ding
Bao-Guo
BG
Greenland
Sander
S
He
Na
N
Jiang
Qingwu
Q
Kheifets
Leeka
L
Le
Anh
A
Lee
Yuan-Chin Amy
YC
Liu
Simin
S
Lu
Ming-Lan
ML
Mao
Jenny T
JT
Morgenstern
Hal
H
Mu
Li-Na
LN
Pantuck
Allan
A
Papp
Jeanette C
JC
Park
Sungshim Lani
SL
Rao
Jian Yu
JY
Reuter
Victor E
VE
Tashkin
Donald P
DP
Wang
Hua
H
You
Nai-Chieh Y
NC
Yu
Shun-Zhang
SZ
Zhao
Jin-Kou
JK
Belldegrun
Arie
A
Zhang
Zuo-Feng
ZF
D000328:Adult; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D007822:Laryngeal Neoplasms / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics*; D009959:Oropharyngeal Neoplasms / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012907:Smoking / Q000235:genetics*