title: Single nucleotide polymorphisms of 8 inflammation-related genes and their associations with smoking-related cancers.
abstract: 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.
authors.affiliation: Department of Epidemiology, University of California, Los Angeles (UCLA) School of Public Health, Los Angeles, CA, USA.
authors.forename: Sam S
authors.initials: SS
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authors.forename: Shen-Chih
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authors.lastname: Chang
authors.forename: Lin
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authors.lastname: Cai
authors.forename: Carlos
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authors.lastname: Cordon-Cardo
authors.forename: Bao-Guo
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authors.lastname: Greenland
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authors.forename: Qingwu
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authors.lastname: Kheifets
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authors.forename: Yuan-Chin Amy
authors.initials: YC
authors.lastname: Lee
authors.forename: Simin
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authors.lastname: Liu
authors.forename: Ming-Lan
authors.initials: ML
authors.lastname: Lu
authors.forename: Jenny T
authors.initials: JT
authors.lastname: Mao
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authors.lastname: Morgenstern
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authors.forename: Sungshim Lani
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authors.lastname: Park
authors.forename: Jian Yu
authors.initials: JY
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: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Nai-Chieh Y
authors.initials: NC
authors.lastname: You
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: 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*