Association analyses identify multiple new lung cancer susceptibility loci and their interactions with smoking in the Chinese population

Nat Genet. 2012 Jul 15;44(8):895-9. doi: 10.1038/ng.2351.

Abstract

To find additional susceptibility loci for lung cancer, we tested promising associations from our previous genome-wide association study (GWAS) of lung cancer in the Chinese population in an extended validation sample size of 7,436 individuals with lung cancer (cases) and 7,483 controls. We found genome-wide significant (P < 5.0 × 10(-8)) evidence for three additional lung cancer susceptibility loci at 10p14 (rs1663689, close to GATA3, P = 2.84 × 10(-10)), 5q32 (rs2895680 in PPP2R2B-STK32A-DPYSL3, P = 6.60 × 10(-9)) and 20q13.2 (rs4809957 in CYP24A1, P = 1.20 × 10(-8)). We also found consistent associations for rs247008 at 5q31.1 (IL3-CSF2-P4HA2, P = 7.68 × 10(-8)) and rs9439519 at 1p36.32 (AJAP1-NPHP4, P = 3.65 × 10(-6)). Four of these loci showed evidence for interactions with smoking dose (P = 1.72 × 10(-10), P = 5.07 × 10(-3), P = 6.77 × 10(-3) and P = 4.49 × 10(-2) for rs2895680, rs4809957, rs247008 and rs9439519, respectively). These results advance our understanding of lung cancer susceptibility and highlight potential pathways that integrate genetic variants and smoking in the development of lung cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian Continental Ancestry Group / genetics*
  • Case-Control Studies
  • China
  • GATA3 Transcription Factor / genetics
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Lung Neoplasms / etiology*
  • Lung Neoplasms / genetics*
  • Muscle Proteins / genetics
  • Nerve Tissue Proteins / genetics
  • Polymorphism, Single Nucleotide
  • Protein Phosphatase 2 / genetics
  • Smoking / adverse effects*
  • Smoking / genetics*
  • Steroid Hydroxylases / genetics
  • Vitamin D3 24-Hydroxylase

Substances

  • DPYSL3 protein, human
  • GATA3 Transcription Factor
  • GATA3 protein, human
  • Muscle Proteins
  • Nerve Tissue Proteins
  • Steroid Hydroxylases
  • CYP24A1 protein, human
  • Vitamin D3 24-Hydroxylase
  • PPP2R2B protein, human
  • Protein Phosphatase 2