title: Genome-wide Gene-Asbestos Exposure Interaction Association Study Identifies a Common Susceptibility Variant on 22q13.31 Associated with Lung Cancer Risk.
abstract: BACKGROUND
  Occupational asbestos exposure has been found to increase lung cancer risk in epidemiologic studies.
  
  
  METHODS
  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, in silico 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 de novo genotyping to replicate the results from the in silico 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.
  
  
  RESULTS
  We observed significantly increased lung cancer risk among MIRLET7BHG (MIRLET7B host gene located at 22q13.31) polymorphisms rs13053856, rs11090910, rs11703832, and rs12170325 heterozygous and homozygous variant allele(s) carriers (P < 5 × 10(-7) 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.
  
  
  CONCLUSIONS
  Our findings suggest that MIRLET7BHG polymorphisms may be important predictive markers for asbestos exposure-related lung cancer.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Environmental and Occupational Medicine and Epidemiology Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts. Institute of Environmental Health, College of Public Health, National Taiwan University, Taipei, Taiwan.
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Liu
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unit U754, Villejuif, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Stücker
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington. Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington. Department of Otolaryngology, Head and Neck Surgery, School of Medicine, University of Washington, Seattle, Washington.
authors.forename: Chu
authors.initials: C
authors.lastname: Chen
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Gary
authors.initials: G
authors.lastname: Goodman
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Michelle K
authors.initials: MK
authors.lastname: McHugh
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Biomath/Biostatistics Program, The University of Texas Graduate School for Biomedical Sciences, Houston, Texas.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: D'Amelio
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Etzel
authors.affiliation: Environmental and Occupational Medicine and Epidemiology Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Su
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Xihong
authors.initials: X
authors.lastname: Lin
authors.affiliation: Environmental and Occupational Medicine and Epidemiology Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts. Department of Medicine, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts. dchris@hsph.harvard.edu.
authors.forename: David C
authors.initials: DC
authors.lastname: Christiani
mesh_terms: D000368:Aged; D001194:Asbestos / Q000009:adverse effects*; D001900:Boston / Q000453:epidemiology; D004273:DNA, Neoplasm / Q000235:genetics; D004843:Epistasis, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000139:chemically induced / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects*; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D004273:DNA, Neoplasm; D001194:Asbestos