title: 15q12 variants, sputum gene promoter hypermethylation, and lung cancer risk: a GWAS in smokers.
abstract: BACKGROUND
  Lung cancer is the leading cause of cancer-related mortality worldwide. Detection of promoter hypermethylation of tumor suppressor genes in exfoliated cells from the lung provides an assessment of field cancerization that in turn predicts lung cancer. The identification of genetic determinants for this validated cancer biomarker should provide novel insights into mechanisms underlying epigenetic reprogramming during lung carcinogenesis.
  
  
  METHODS
  A genome-wide association study using generalized estimating equations and logistic regression models was conducted in two geographically independent smoker cohorts to identify loci affecting the propensity for cancer-related gene methylation that was assessed by a 12-gene panel interrogated in sputum. All statistical tests were two-sided.
  
  
  RESULTS
  Two single nucleotide polymorphisms (SNPs) at 15q12 (rs73371737 and rs7179575) that drove gene methylation were discovered and replicated with rs73371737 reaching genome-wide significance (P = 3.3×10(-8)). A haplotype carrying risk alleles from the two 15q12 SNPs conferred 57% increased risk for gene methylation (P = 2.5×10(-9)). Rs73371737 reduced GABRB3 expression in lung cells and increased risk for smoking-induced chronic mucous hypersecretion. Furthermore, subjects with variant homozygote of rs73371737 had a two-fold increase in risk for lung cancer (P = .0043). Pathway analysis identified DNA double-strand break repair by homologous recombination (DSBR-HR) as a major pathway affecting susceptibility for gene methylation that was validated by measuring chromatid breaks in lymphocytes challenged by bleomycin.
  
  
  CONCLUSIONS
  A functional 15q12 variant was identified as a risk factor for gene methylation and lung cancer. The associations could be mediated by GABAergic signaling that drives the smoking-induced mucous cell metaplasia. Our findings also substantiate DSBR-HR as a critical pathway driving epigenetic gene silencing.
authors.affiliation: : Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
authors.forename: Shuguang
authors.initials: S
authors.lastname: Leng
authors.affiliation: : Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
authors.forename: Yushi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: : Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
authors.forename: Joel L
authors.initials: JL
authors.lastname: Weissfeld
authors.affiliation: : Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Thomas
authors.affiliation: : Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
authors.forename: Younghun
authors.initials: Y
authors.lastname: Han
authors.affiliation: : Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
authors.forename: Maria A
authors.initials: MA
authors.lastname: Picchi
authors.affiliation: : Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Edlund
authors.affiliation: : Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
authors.forename: Randall P
authors.initials: RP
authors.lastname: Willink
authors.affiliation: : Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
authors.forename: Autumn L
authors.initials: AL
authors.lastname: Gaither Davis
authors.affiliation: : Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
authors.forename: Kieu C
authors.initials: KC
authors.lastname: Do
authors.affiliation: : Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
authors.forename: Tomoko
authors.initials: T
authors.lastname: Nukui
authors.affiliation: : Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
authors.forename: Xiequn
authors.initials: X
authors.lastname: Zhang
authors.affiliation: : Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Burki
authors.affiliation: : Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
authors.forename: David
authors.initials: D
authors.lastname: Van Den Berg
authors.affiliation: : Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
authors.forename: Marjorie
authors.initials: M
authors.lastname: Romkes
authors.affiliation: : Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
authors.forename: W James
authors.initials: WJ
authors.lastname: Gauderman
authors.affiliation: : Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
authors.forename: Richard E
authors.initials: RE
authors.lastname: Crowell
authors.affiliation: : Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
authors.forename: Yohannes
authors.initials: Y
authors.lastname: Tesfaigzi
authors.affiliation: : Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
authors.forename: Christine A
authors.initials: CA
authors.lastname: Stidley
authors.affiliation: : Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Amos
authors.affiliation: : Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
authors.forename: Jill M
authors.initials: JM
authors.lastname: Siegfried
authors.affiliation: : Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
authors.forename: Frank D
authors.initials: FD
authors.lastname: Gilliland
authors.affiliation: : Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS). sbelinsk@LRRI.org.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Belinsky
mesh_terms: D000328:Adult; D000368:Aged; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D015203:Reproducibility of Results; D012306:Risk; D012907:Smoking / Q000009:adverse effects*; D013183:Sputum