Multistage analysis of variants in the inflammation pathway and lung cancer risk in smokers.

Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology
Margaret R SpitzChristopher I Amos

Abstract

Tobacco-induced lung cancer is characterized by a deregulated inflammatory microenvironment. Variants in multiple genes in inflammation pathways may contribute to risk of lung cancer. We therefore conducted a three-stage comprehensive pathway analysis (discovery, replication, and meta-analysis) of inflammation gene variants in ever-smoking lung cancer cases and controls. A discovery set (1,096 cases and 727 controls) and an independent and nonoverlapping internal replication set (1,154 cases and 1,137 controls) were derived from an ongoing case-control study. For discovery, we used an iSelect BeadChip to interrogate a comprehensive panel of 11,737 inflammation pathway single-nucleotide polymorphisms (SNP) and selected nominally significant (P < 0.05) SNPs for internal replication. There were six SNPs that achieved statistical significance (P < 0.05) in the internal replication data set with concordant risk estimates for former smokers and five concordant and replicated SNPs in current smokers. Replicated hits were further tested in a subsequent meta-analysis using external data derived from two published genome-wide association studies (GWAS) and a case-control study. Two of these variants (a BCL2L14 SNP in former smokers and a...Continue Reading

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Citations

Jun 5, 2014·Human Genetics·Ming LiUNKNOWN National Birth Defect Prevention Study
Mar 5, 2013·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Margaret R SpitzAnn G Schwartz
Feb 19, 2014·Birth Defects Research. Part A, Clinical and Molecular Teratology·Charlotte A HobbsUNKNOWN National Birth Defects Prevention Study
May 1, 2015·International Journal of Cancer. Journal International Du Cancer·Gad RennertJoshua E Muscat
Sep 1, 2015·Journal of the National Cancer Institute·Rayjean J HungUNKNOWN GAME-ON Network
Nov 12, 2019·International Journal of Cancer. Journal International Du Cancer·Donovan WatzaAnn G Schwartz
Mar 25, 2017·Neuro-oncology·Yen-Tsung HuangDominique S Michaud
May 10, 2016·Medical Science Monitor : International Medical Journal of Experimental and Clinical Research·Bing ZhouJian Shen

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