Author of

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  P2.05 - Poster Session/ Prevention and Tobacco Control (ID 216)

  • Event: WCLC 2015
  • Type: Poster
  • Track: Prevention and Tobacco Control
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)

  • 14608

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    P2.05-008 - The Role of Haplotype in 15q25.1 Locus in Lung Cancer Risk: Results of Scanning Chromosome 15 (ID 1015)

    09:30 - 09:30  |  Author(s): C.I. Amos
    • Abstract
    • Slides

    Background:
    The role of haplotypes and the interaction of haplotypes and smoking exposure in the etiology of lung cancer have not been well characterized.
    
    Methods:
    We analyzed data from an Italian population-based case-control study among 1815 lung cancer cases and 1959 healthy controls in discovery phase and performed a validation using a case-control study comprising 2983 lung cancer cases and 3553 healthy controls of European ancestry for replication. Haplotype analyses and logistic regression were used to explore the casual haplotype and its association with lung cancer risk.
    
    Results:
    Sliding window haplotype analysis within chromosome 15, evaluating 4,722,250 haplotypes, and pair-wise haplotype analysis identified that rs16969968-rs588765 was the most significant haplotype associated with lung cancer risk (omnibus p = 8.35 × 10[−15] in discovery and 7.26× 10[−14] in replication), and improved the prediction of case status over that provided by the individual SNPs rs16969968 or rs588765 (likelihood ratio test p = 0.006 for rs16969968 and 3.83 × 10[−14] for rs588765 in discovery, 0.009 for rs16969968 and 4.62 × 10[−13] for rs588765 in replication, compared with rs16969968-rs588765). Compared to the wild type homozygous diplotype, the CA/CA homozygote exhibited an approximately 2-fold increase risk for lung cancer (OR = 2.12; 95% CI, 1.46 - 3.07 in discovery, and OR = 2.01; 95% CI, 1.51 - 2.67 in replication). Even among never-smokers, individuals with CA/CA homozygous diplotype had an increased risk of lung cancer with borderline significance in the discovery (adjusted OR = 1.75, 95% CI, 0.96 – 3.19) and statistical significance in the replication (adjusted OR = 2.10, 95% CI, 1.12 – 3.96), compared to those with combined genotypes (CG/CG + CG/TG). We also found that smokers with the CA/CA homozygous diplotype had a more than 13-fold increased risk for lung cancer in the discovery (adjusted OR = 13.42, 95% CI, 8.21 – 21.95) and 15-fold increased risk in the replication (adjusted OR = 15.52, 95% CI, 9.85 – 24.45), compared to nonsmokers with the combined genotypes (CG/CG + CG/TG).
    
    Conclusion:
    The rs16969968-rs588765 haplotype modifies lung cancer risk more than effects from individual variations at rs16969968 or rs588765, may be a marker of genetic susceptibility to lung cancer even among never-smokers, and has a joint effect with smoking exposure on lung risk.This knowledge may facilitate our understanding of lung cancer etiology and identifies a particularly high risk.
    
    

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