Abstract
<div>Abstract<p><b>Background:</b> Occupational asbestos exposure has been found to increase lung cancer risk in epidemiologic studies.</p><p><b>Methods:</b> We conducted an asbestos exposure–gene interaction analyses among several Caucasian populations who were current or ex-smokers. The discovery phase included 833 Caucasian cases and 739 Caucasian controls, and used a genome-wide association study (GWAS) to identify single-nucleotide polymorphisms (SNP) with gene–asbestos interaction effects. The top ranked SNPs from the discovery phase were replicated within the International Lung and Cancer Consortium (ILCCO). First, <i>in silico</i> replication was conducted in those groups that had GWAS and asbestos exposure data, including 1,548 cases and 1,527 controls. This step was followed by <i>de novo</i> genotyping to replicate the results from the <i>in silico</i> replication, and included 1,539 cases and 1,761 controls. Multiple logistic regression was used to assess the SNP–asbestos exposure interaction effects on lung cancer risk.</p><p><b>Results:</b> We observed significantly increased lung cancer risk among <i>MIRLET7BHG</i> (<i>MIRLET7B host gene</i> located at 22q13.31) polymorphisms rs13053856, rs11090910, rs11703832, and rs12170325 heterozygous and homozygous variant allele(s) carriers (<i>P</i> < 5 × 10<sup>−7</sup> by likelihood ratio test; df = 1). Among the heterozygous and homozygous variant allele(s) carriers of polymorphisms rs13053856, rs11090910, rs11703832, and rs12170325, each unit increase in the natural log-transformed asbestos exposure score was associated with age-, sex-, smoking status, and center-adjusted ORs of 1.34 [95% confidence interval (CI), 1.18–1.51], 1.24 (95% CI, 1.14–1.35), 1.28 (95% CI, 1.17–1.40), and 1.26 (95% CI, 1.15–1.38), respectively, for lung cancer risk.</p><p><b>Conclusion:</b> Our findings suggest that <i>MIRLET7BHG</i> polymorphisms may be important predictive markers for asbestos exposure–related lung cancer.</p><p><b>Impact:</b> To our knowledge, our study is the first report using a systematic genome-wide analysis in combination with detailed asbestos exposure data and replication to evaluate asbestos-associated lung cancer risk. <i>Cancer Epidemiol Biomarkers Prev; 24(10); 1564–73. ©2015 AACR</i>.</p></div>
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