Single nucleotide polymorphisms of 8 inflammation-related genes and their associations with smoking-related cancers

✍ Scribed by Sam S. Oh; Shen-Chih Chang; Lin Cai; Carlos Cordon-Cardo; Bao-Guo Ding; Sander Greenland; Na He; Qingwu Jiang; Leeka Kheifets; Anh Le; Yuan-Chin Amy Lee; Simin Liu; Ming-Lan Lu; Jenny T. Mao; Hal Morgenstern; Li-Na Mu; Allan Pantuck; Jeanette C. Papp; Sungshim Lani Park; Jian Yu Rao; Victor E. Reuter; Donald P. Tashkin; Hua Wang; Nai-Chieh Y. You; Shun-Zhang Yu; Jin-Kou Zhao; Arie Belldegrun; Zuo-Feng Zhang

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: French
• Weight: 465 KB
• Volume: 127
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.25214

✦ Synopsis

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.