Multistage analysis of variants in the Inflammation pathway and lung cancer risk in smokers
BACKGROUND: 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. METHODS: We therefore conducted a three-stage comprehensive pathway analysis (discovery, replication and...
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2012
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| 在線閱讀: | https://ncbi.nlm.nih.gov/pmc/articles/PMC3487592/ https://ncbi.nlm.nih.gov/pubmed/22573796 https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1158/1055-9965.EPI-12-0352-T |
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pubmed-34875922012-11-02 Multistage analysis of variants in the Inflammation pathway and lung cancer risk in smokers Spitz, Margaret R. Gorlov, Ivan P. Dong, Qiong Wu, Xifeng Chen, Wei Chang, David W. Etzel, Carol J. Caporaso, Neil E. Zhao, Yang Christiani, David C. Brennan, Paul Albanes, Demetrius Shi, Jianxin Thun, Michael Landi, Maria Teresa Amos, Christopher I. Cancer Epidemiol Biomarkers Prev Article BACKGROUND: 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. METHODS: 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 (1096 cases; 727 controls) and an independent and non-overlapping internal replication set (1154 cases; 1137 controls) were derived from an ongoing case-control study. For discovery, we used an iSelect BeadChip to interrogate a comprehensive panel of 11737 inflammation pathway SNPs and selected nominally significant (p<0.05) SNPs for internal replication. RESULTS: There were 6 SNPs that achieved statistical significance (p<0.05) in the internal replication dataset with concordant risk estimates for former smokers and 5 concordant and replicated SNPs in current smokers. Replicated hits were further tested in a subsequent meta-analysis using external data derived from two published GWAS and a case-control study. Two of these variants (a BCL2L14 SNP in former smokers and a SNP in IL2RB in current smokers) were further validated. In risk score analyses, there was a 26% increase in risk with each additional adverse allele when we combined the genotyped SNP and the most significant imputed SNP in IL2RB in current smokers and a 36% similar increase in risk for former smokers associated with genotyped and imputed BCL2L14 SNPs. CONCLUSIONS/IMPACT: Before they can be applied for risk prediction efforts, these SNPs should be subject to further external replication and more extensive fine mapping studies. 2012-05-09 2012-07 /pmc/articles/PMC3487592/ /pubmed/22573796 http://dx.doi.org/10.1158/1055-9965.EPI-12-0352-T Text en |
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Article Spitz, Margaret R. Gorlov, Ivan P. Dong, Qiong Wu, Xifeng Chen, Wei Chang, David W. Etzel, Carol J. Caporaso, Neil E. Zhao, Yang Christiani, David C. Brennan, Paul Albanes, Demetrius Shi, Jianxin Thun, Michael Landi, Maria Teresa Amos, Christopher I. Multistage analysis of variants in the Inflammation pathway and lung cancer risk in smokers |
| description |
BACKGROUND: 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. METHODS: 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 (1096 cases; 727 controls) and an independent and non-overlapping internal replication set (1154 cases; 1137 controls) were derived from an ongoing case-control study. For discovery, we used an iSelect BeadChip to interrogate a comprehensive panel of 11737 inflammation pathway SNPs and selected nominally significant (p<0.05) SNPs for internal replication. RESULTS: There were 6 SNPs that achieved statistical significance (p<0.05) in the internal replication dataset with concordant risk estimates for former smokers and 5 concordant and replicated SNPs in current smokers. Replicated hits were further tested in a subsequent meta-analysis using external data derived from two published GWAS and a case-control study. Two of these variants (a BCL2L14 SNP in former smokers and a SNP in IL2RB in current smokers) were further validated. In risk score analyses, there was a 26% increase in risk with each additional adverse allele when we combined the genotyped SNP and the most significant imputed SNP in IL2RB in current smokers and a 36% similar increase in risk for former smokers associated with genotyped and imputed BCL2L14 SNPs. CONCLUSIONS/IMPACT: Before they can be applied for risk prediction efforts, these SNPs should be subject to further external replication and more extensive fine mapping studies. |
| author |
Spitz, Margaret R. Gorlov, Ivan P. Dong, Qiong Wu, Xifeng Chen, Wei Chang, David W. Etzel, Carol J. Caporaso, Neil E. Zhao, Yang Christiani, David C. Brennan, Paul Albanes, Demetrius Shi, Jianxin Thun, Michael Landi, Maria Teresa Amos, Christopher I. |
| author_facet |
Spitz, Margaret R. Gorlov, Ivan P. Dong, Qiong Wu, Xifeng Chen, Wei Chang, David W. Etzel, Carol J. Caporaso, Neil E. Zhao, Yang Christiani, David C. Brennan, Paul Albanes, Demetrius Shi, Jianxin Thun, Michael Landi, Maria Teresa Amos, Christopher I. |
| author_sort |
Spitz, Margaret R. |
| title |
Multistage analysis of variants in the Inflammation pathway and lung cancer risk in smokers |
| title_short |
Multistage analysis of variants in the Inflammation pathway and lung cancer risk in smokers |
| title_full |
Multistage analysis of variants in the Inflammation pathway and lung cancer risk in smokers |
| title_fullStr |
Multistage analysis of variants in the Inflammation pathway and lung cancer risk in smokers |
| title_full_unstemmed |
Multistage analysis of variants in the Inflammation pathway and lung cancer risk in smokers |
| title_sort |
multistage analysis of variants in the inflammation pathway and lung cancer risk in smokers |
| publishDate |
2012 |
| url |
https://ncbi.nlm.nih.gov/pmc/articles/PMC3487592/ https://ncbi.nlm.nih.gov/pubmed/22573796 https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1158/1055-9965.EPI-12-0352-T |
| _version_ |
1761591914653548544 |