title: Inherited variation at chromosome 12p13.33, including RAD52, influences the risk of squamous cell lung carcinoma.
abstract: Although lung cancer is largely caused by tobacco smoking, inherited genetic factors play a role in its etiology. Genome-wide association studies in Europeans have only robustly demonstrated 3 polymorphic variations that influence the risk of lung cancer. Tumor heterogeneity may have hampered the detection of association signal when all lung cancer subtypes were analyzed together. In a genome-wide association study of 5,355 European ever-smoker lung cancer patients and 4,344 smoking control subjects, we conducted a pathway-based analysis in lung cancer histologic subtypes with 19,082 single-nucleotide polymorphisms mapping to 917 genes in the HuGE-defined "inflammation" pathway. We identified a susceptibility locus for squamous cell lung carcinoma at 12p13.33 (RAD52, rs6489769) and replicated the association in 3 independent studies totaling 3,359 squamous cell lung carcinoma cases and 9,100 controls (OR = 1.20, P(combined) = 2.3 × 10(-8)).
  
  
  CONCLUSIONS
  The combination of pathway-based approaches and information on disease-specific subtypes can improve the identification of cancer susceptibility loci in heterogeneous diseases.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, Maryland 20892, USA.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Shi
authors.forename: Nilanjan
authors.initials: N
authors.lastname: Chatterjee
authors.forename: Melissa
authors.initials: M
authors.lastname: Rotunno
authors.forename: Yufei
authors.initials: Y
authors.lastname: Wang
authors.forename: Angela C
authors.initials: AC
authors.lastname: Pesatori
authors.forename: Dario
authors.initials: D
authors.lastname: Consonni
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: William
authors.initials: W
authors.lastname: Wheeler
authors.forename: Peter
authors.initials: P
authors.lastname: Broderick
authors.forename: Marc
authors.initials: M
authors.lastname: Henrion
authors.forename: Timothy
authors.initials: T
authors.lastname: Eisen
authors.forename: Zhaoming
authors.initials: Z
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Qiong
authors.initials: Q
authors.lastname: Dong
authors.forename: Demetrius
authors.initials: D
authors.lastname: Albanes
authors.forename: Michael
authors.initials: M
authors.lastname: Thun
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Spitz
authors.forename: Pier Alberto
authors.initials: PA
authors.lastname: Bertazzi
authors.forename: Neil E
authors.initials: NE
authors.lastname: Caporaso
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Amos
authors.forename: Richard S
authors.initials: RS
authors.lastname: Houlston
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Landi
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000453:epidemiology / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D002881:Chromosomes, Human, Pair 12; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D051721:Rad52 DNA Repair and Recombination Protein / Q000235:genetics*; D012907:Smoking / Q000453:epidemiology / Q000235:genetics; D013781:Texas / Q000453:epidemiology; D006113:United Kingdom / Q000453:epidemiology
chemical_list: C497194:RAD52 protein, human; D051721:Rad52 DNA Repair and Recombination Protein