Genome-wide association study identifies a novel susceptibility locus at 12q23.1 for lung squamous cell carcinoma in han chinese

PLoS Genet. 2013;9(1):e1003190. doi: 10.1371/journal.pgen.1003190. Epub 2013 Jan 17.

Abstract

Adenocarcinoma (AC) and squamous cell carcinoma (SqCC) are two major histological subtypes of lung cancer. Genome-wide association studies (GWAS) have made considerable advances in the understanding of lung cancer susceptibility. Obvious heterogeneity has been observed between different histological subtypes of lung cancer, but genetic determinants in specific to lung SqCC have not been systematically investigated. Here, we performed the GWAS analysis specifically for lung SqCC in 833 SqCC cases and 3,094 controls followed by a two-stage replication in additional 2,223 lung SqCC cases and 6,409 controls from Chinese populations. We found that rs12296850 in SLC17A8-NR1H4 gene region at12q23.1 was significantly associated with risk of lung SqCC at genome-wide significance level [additive model: odds ratio (OR) = 0.78, 95% confidence interval (CI) = 0.72-0.84, P = 1.19×10(-10)]. Subjects carrying AG or GG genotype had a 26% (OR = 0.74, 95% CI = 0.67-0.81) or 32% (OR = 0.68, 95% CI = 0.56-0.83) decreased risk of lung SqCC, respectively, as compared with AA genotype. However, we did not observe significant association between rs12296850 and risk of lung AC in a total of 4,368 cases with lung AC and 9,486 controls (OR = 0.96, 95% CI = 0.90-1.02, P = 0.173). These results indicate that genetic variations on chromosome 12q23.1 may specifically contribute to lung SqCC susceptibility in Chinese population.

Publication types

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

MeSH terms

  • Asian Continental Ancestry Group
  • Carcinoma, Squamous Cell* / genetics
  • Carcinoma, Squamous Cell* / pathology
  • Chromosomes, Human, Pair 12 / genetics
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study*
  • Humans
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • Polymorphism, Single Nucleotide
  • Receptors, Cytoplasmic and Nuclear / genetics*
  • Risk Factors
  • Vesicular Glutamate Transport Proteins / genetics*

Substances

  • Receptors, Cytoplasmic and Nuclear
  • SLC17A8 protein, human
  • Vesicular Glutamate Transport Proteins
  • farnesoid X-activated receptor