title: Effect of occupational exposures on lung cancer susceptibility: a study of gene-environment interaction analysis.
abstract: BACKGROUND
  Occupational exposures are known risk factors for lung cancer. Role of genetically determined host factors in occupational exposure-related lung cancer is unclear.
  
  
  METHODS
  We used genome-wide association (GWA) data from a case-control study conducted in 6 European countries from 1998 to 2002 to identify gene-occupation interactions and related pathways for lung cancer risk. GWA analysis was performed for each exposure using logistic regression and interaction term for genotypes, and exposure was included in this model. Both SNP-based and gene-based interaction P values were calculated. Pathway analysis was performed using three complementary methods, and analyses were adjusted for multiple comparisons. We analyzed 312,605 SNPs and occupational exposure to 70 agents from 1,802 lung cancer cases and 1,725 cancer-free controls.
  
  
  RESULTS
  Mean age of study participants was 60.1 ± 9.1 years and 75% were male. Largest number of significant associations (P ≤ 1 × 10(-5)) at SNP level was demonstrated for nickel, brick dust, concrete dust, and cement dust, and for brick dust and cement dust at the gene-level (P ≤ 1 × 10(-4)). Approximately 14 occupational exposures showed significant gene-occupation interactions with pathways related to response to environmental information processing via signal transduction (P < 0.001 and FDR < 0.05). Other pathways that showed significant enrichment were related to immune processes and xenobiotic metabolism.
  
  
  CONCLUSIONS
  Our findings suggest that pathways related to signal transduction, immune process, and xenobiotic metabolism may be involved in occupational exposure-related lung carcinogenesis.
  
  
  CONCLUSIONS
  Our study exemplifies an integrative approach using pathway-based analysis to demonstrate the role of genetic variants in occupational exposure-related lung cancer susceptibility. Cancer Epidemiol Biomarkers Prev; 24(3); 570-9. ©2015 AACR.
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York. jyoti.malhotra@mountsinai.org.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Malhotra
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Samantha
authors.initials: S
authors.lastname: Sartori
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
authors.affiliation: Russian Cancer Research Center, Moscow, Russia.
authors.forename: David
authors.initials: D
authors.lastname: Zaridze
authors.affiliation: Department of Epidemiology, The Nofer Institute of Occupational Medicine, Lodz, Poland.
authors.forename: Neonila
authors.initials: N
authors.lastname: Szeszenia-Dabrowska
authors.affiliation: Department of Epidemiology, The Nofer Institute of Occupational Medicine, Lodz, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Świątkowska
authors.affiliation: National Institute of Environmental Health, Budapest, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Rudnai
authors.affiliation: M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Lissowska
authors.affiliation: Department of Occupational Health, Specialized State Health Institute, Banska Bystrica, Slovakia.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Fabianova
authors.affiliation: National Institute of Public Health, Bucharest, Romania.
authors.forename: Dana
authors.initials: D
authors.lastname: Mates
authors.affiliation: Institute of Hygiene and Epidemiology, Charles University, First Faculty of Medicine, Prague, Czech Republic.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Bencko
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Valerie
authors.initials: V
authors.lastname: Gaborieau
authors.affiliation: Centre for Research in Epidemiology and Population Health, INSERM, Villejuif, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Stücker
authors.affiliation: Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute and MF MU Brno, Brno, Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Foretova
authors.affiliation: Department of Preventive Medicine, Faculty of Medicine, Palacky University, Olomouc, Czech Republic.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Janout
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Paolo
authors.initials: P
authors.lastname: Boffetta
mesh_terms: D016022:Case-Control Studies; D005060:Europe / Q000453:epidemiology; D005260:Female; D059647:Gene-Environment Interaction; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009784:Occupational Diseases / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D016273:Occupational Exposure / Q000009:adverse effects / Q000706:statistics & numerical data*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D015398:Signal Transduction