title: Gene by Environment Investigation of Incident Lung Cancer Risk in African-Americans.
abstract: BACKGROUND
  Genome-wide association studies have identified polymorphisms linked to both smoking exposure and risk of lung cancer. The degree to which lung cancer risk is driven by increased smoking, genetics, or gene-environment interactions is not well understood.
  
  
  METHODS
  We analyzed associations between 28 single nucleotide polymorphisms (SNPs) previously associated with smoking quantity and lung cancer in 7156 African-American females in the Women's Health Initiative (WHI), then analyzed main effects of top nominally significant SNPs and interactions between SNPs, cigarettes per day (CPD) and pack-years for lung cancer in an independent, multi-center case-control study of African-American females and males (1078 lung cancer cases and 822 controls).
  
  
  RESULTS
  Nine nominally significant SNPs for CPD in WHI were associated with incident lung cancer (corrected p-values from 0.027 to 6.09 × 10(-5)). CPD was found to be a nominally significant effect modifier between SNP and lung cancer for six SNPs, including CHRNA5 rs2036527[A](betaSNP*CPD = - 0.017, p = 0.0061, corrected p = 0.054), which was associated with CPD in a previous genome-wide meta-analysis of African-Americans.
  
  
  CONCLUSIONS
  These results suggest that chromosome 15q25.1 variants are robustly associated with CPD and lung cancer in African-Americans and that the allelic dose effect of these polymorphisms on lung cancer risk is most pronounced in lighter smokers.
authors.affiliation: Division of General Medical Disciplines, Department of Medicine, Stanford University School of Medicine, Stanford, CA, United States.
authors.forename: Sean P
authors.initials: SP
authors.lastname: David
authors.affiliation: Stanford Prevention Research Center, Department of Medicine, Stanford University School of Medicine, Stanford, CA, United States.
authors.forename: Ange
authors.initials: A
authors.lastname: Wang
authors.affiliation: Quantitative Sciences Unit, Department of Medicine, Stanford University School of Medicine, Stanford, CA, United States.
authors.forename: Kristopher
authors.initials: K
authors.lastname: Kapphahn
authors.affiliation: Quantitative Sciences Unit, Department of Medicine, Stanford University School of Medicine, Stanford, CA, United States.
authors.forename: Haley
authors.initials: H
authors.lastname: Hedlin
authors.affiliation: Quantitative Sciences Unit, Department of Medicine, Stanford University School of Medicine, Stanford, CA, United States.
authors.forename: Manisha
authors.initials: M
authors.lastname: Desai
authors.affiliation: Stanford Prevention Research Center, Department of Medicine, Stanford University School of Medicine, Stanford, CA, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Henderson
authors.affiliation: Quantitative Sciences Unit, Department of Medicine, Stanford University School of Medicine, Stanford, CA, United States.
authors.forename: Lingyao
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, United States; Program in Cancer Genetics, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, United States.
authors.forename: Kyle M
authors.initials: KM
authors.lastname: Walsh
authors.affiliation: Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, United States.
authors.forename: Ann G
authors.initials: AG
authors.lastname: Schwartz
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, United States.
authors.forename: John K
authors.initials: JK
authors.lastname: Wiencke
authors.affiliation: Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, United States.
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Spitz
authors.affiliation: Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, United States.
authors.forename: Angela S
authors.initials: AS
authors.lastname: Wenzlaff
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, United States.
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Wrensch
authors.affiliation: Center for Primary Care and Prevention, Department of Family Medicine, Warren Alpert Medical School of Brown University, Pawtucket, RI, United States.
authors.forename: Charles B
authors.initials: CB
authors.lastname: Eaton
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
authors.forename: Helena
authors.initials: H
authors.lastname: Furberg
authors.affiliation: Division of Public Health Sciences, Department of Biostatistical Sciences, Wake Forest University Health Sciences, Winston-Salem, NC, United States.
authors.forename: W
authors.initials: W
authors.lastname: Mark Brown
authors.affiliation: Department of Biostatistics & Bioinformatics, Duke University School of Medicine, Durham, NC, United States.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Goldstein
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, United States.
authors.forename: Themistocles
authors.initials: T
authors.lastname: Assimes
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, CA, United States.
authors.forename: Hua
authors.initials: H
authors.lastname: Tang
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, United States.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Kooperberg
authors.affiliation: Kaiser Permanente, Division of Research, Oakland, CA 94612, United States.
authors.forename: Charles P
authors.initials: CP
authors.lastname: Quesenberry
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH, United States.
authors.forename: Hilary
authors.initials: H
authors.lastname: Tindle
authors.affiliation: Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, United States.
authors.forename: Manali I
authors.initials: MI
authors.lastname: Patel
authors.affiliation: Departments of Genetics, Geisel School of Medicine at Dartmouth, Hanover, NH, United States; Community and Family Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH, United States.
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Amos
authors.affiliation: BioRealm, Culver City, CA, United States.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Bergen
authors.affiliation: Quantitative Sciences Unit, Department of Medicine, Stanford University School of Medicine, Stanford, CA, United States.
authors.forename: Gary E
authors.initials: GE
authors.lastname: Swan
authors.affiliation: Stanford Prevention Research Center, Department of Medicine, Stanford University School of Medicine, Stanford, CA, United States.
authors.forename: Marcia L
authors.initials: ML
authors.lastname: Stefanick
mesh_terms: D001741:Black or African American; D016022:Case-Control Studies; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D005260:Female; D059647:Gene-Environment Interaction; D060045:Genes, Modifier; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011978:Receptors, Nicotinic / Q000235:genetics; D012907:Smoking / Q000009:adverse effects*
chemical_list: C447158:CHRNA5 protein, human; D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic
keywords: African-Americans; Environment; Genetics; Lung Cancer; Single Nucleotide Polymorphisms; Smoking; rs2036527