title: Apoptosis-Related Single Nucleotide Polymorphisms and the Risk of Non-Small Cell Lung Cancer in Women.
abstract: BACKGROUND
  Germline apoptosis-related single nucleotide polymorphisms (SNPs) have been shown to contribute to the risk of developing non-small cell lung cancer (NSCLC). However, very few studies have looked specifically at apoptosis-related SNPs in a racially-stratified analysis of white and African-American women.
  
  
  METHODS
  We examined the risk of developing NSCLC associated with 98 germline SNPs in 32 apoptosis-related genes among women in a population-based case-control study from the Detroit metropolitan area. We examined 453 cases of NSCLC and 478 control subjects. We used an unconditional logistic regression with a dominant model, stratified by race, and adjusted for age, pack-years smoked, ever/never smoking status, family history of lung cancer, history of COPD, BMI and education.
  
  
  RESULTS
  Our logistic regression identified 3 significant apoptosis-related SNPs in whites (APAF-1,rs1007573;CD40rs3765459, andCD40rs1535045), and 7 significant SNPs (ATM,rs1801516;BAK1,rs513349;TNF,rs1800629;TP63,rs6790167;TP63,rs7613791,TP63,rs35592567 andTP63,rs3856775)in African-Americans. In a downstream analysis, these SNPs were further prioritized utilizing the False Positive Report Percentage (FPRP) methodology and backwards elimination. In whites,APAF-1 (rs1007573),CD40 (rs3765459) andCD40(rs1535045) were all found to be significant by FPRP. In African-Americans,TP63SNPs rs6790167 and rs7613791 were found to have a significant FPRP. In parallel, a backward elimination procedure was used on the 3 significant SNPs in whites and 7 significant SNPs in African-Americans. This procedure identifiedAPAF-1rs1007573 (OR=1.86, 95% CI: 1.17-2.95) andCD40rs1535045 (OR=0.58, 95% CI: 0.40-0.84) as significant independent predictors of risk among whites, andATMrs1801516 (OR=24.15, 95% CI: 3.50-166.55),TNFrs1800629 (OR= 0.42, 95% CI: 0.18-0.99) andTP63rs6790167 (OR: 2.85, 95% CI: 1.33-6.09) as significant, independent predictors in African-Americans.
  
  
  CONCLUSIONS
  In whites, only SNPsAPAF-1rs1007573 andCD40rs1535045 were significant by both FPRP and backwards elimination, while in African-Americans, onlyTP63rs6790167 was significant by both methodologies. Thus, we have identified three promising variants associated with increased risk of NSCLC that warrant additional investigation in future studies.
authors.affiliation: Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD 20850.
authors.forename: Anand
authors.initials: A
authors.lastname: Pathak
authors.affiliation: Population Studies and Disparities Research Program, Karmanos Cancer Institute, Wayne State University, 4100 John R., Mail Code: MM04EP, Detroit, MI 48201.
authors.forename: Angela S
authors.initials: AS
authors.lastname: Wenzlaff
authors.affiliation: Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD 20850.
authors.forename: Paula L
authors.initials: PL
authors.lastname: Hyland
authors.affiliation: Population Studies and Disparities Research Program, Karmanos Cancer Institute, Wayne State University, 4100 John R., Mail Code: MM04EP, Detroit, MI 48201.
authors.forename: Michele L
authors.initials: ML
authors.lastname: Cote
authors.affiliation: Population Studies and Disparities Research Program, Karmanos Cancer Institute, Wayne State University, 4100 John R., Mail Code: MM04EP, Detroit, MI 48201.
authors.forename: Greg R
authors.initials: GR
authors.lastname: Keele
authors.affiliation: Applied Genomics Technology Center and Department of Obstetrics & Gynecology, Wayne State University School of Medicine, CS Mott Center. 275 East Hancock St., Detroit MI 48201.
authors.forename: Susan
authors.initials: S
authors.lastname: Land
authors.affiliation: Preventive Medicine Residency, Department of Epidemiology, University of Michigan School of Public Health, 1415 Washington Heights -M5216 SPH II Ann Arbor, MI 48109.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Boulton
authors.affiliation: Population Studies and Disparities Research Program, Karmanos Cancer Institute, Wayne State University, 4100 John R., Mail Code: MM04EP, Detroit, MI 48201.
authors.forename: Ann G
authors.initials: AG
authors.lastname: Schwartz
keywords: APAF-1; ATM; CD40; TNF; TP63; apoptosis; females; non-small cell lung cancer (NSCLC); single nucleotide polymorphisms