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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.

SUBMITTER: Oh SS

PROVIDER: S-EPMC2932751 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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

Oh Sam S SS 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

International journal of cancer 20101101 9

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-contr ...[more]

PMID: 20112337

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Project description:PurposeTumor capsule is an independent prognostic factor for patients with hepatocellular carcinoma (HCC) and used increasingly to guide clinical decision-making. Considering the genetic complexity for capsule formation and its potential association with hypoxia, the significance of the polymorphisms of hypoxia-related genes in capsule formation and HCC prognosis remains to be elucidated.Patients and methodsPeripheral blood samples from HCC patients were collected in this study. Single nucleotide polymorphism (SNP) genotyping was conducted by the iPLEX chemistry on a matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (Sequenom, Inc.). The demographic and clinical data for the patients were obtained through medical chart review and/or consultation with the treating physicians. SPSS 25.0, R 4.1.1, and PLINK toolset were used to perform statistical analysis.ResultsA total of 183 patients were enrolled, including 88 patients assigned to the capsule group and 95 to the non-capsule group. SLC2A1 rs841858 T allele, SLC2A1 rs2297977 T allele, STAT1 rs1547550 C allele, and STAT1 rs34997637 G allele were associated with significantly increased risk of capsule formation. The genotypes of SLC2A1 rs841858, SLC2A1 rs2297977, STAT1 rs34997637, and STAT1 rs1914408 were significantly associated with the formation of HCC capsule. The polymorphisms of STAT1 rs2066802, STAT1 rs12693591, and HIF1A rs2057482 showed close relationship with the prognosis of HCC patients in the capsule group, while the genotype distributions of CTNNB1 rs4135385, IFNG rs1861494, and SERPINE1 rs2227631 were closely related to the survival of patients in the non-capsule group. Further haplotype analysis suggested that SLC2A1 block 1 and STAT1 block 2 were related to the susceptibility of HCC capsule.ConclusionThe polymorphisms of the hypoxia-related genes (HIF1A, SERPINE1, IFNG, STAT1, CTNNB1, and SLC2A1) were correlated with the formation of HCC capsule. Several SNPs in these genes also showed association with HCC prognosis except SLC2A1. Further functional studies are warranted to explore the underlying mechanisms.

Dataset Information

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

Publications

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

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