Apoptosis-related single nucleotide polymorphisms and the risk of non-small cell lung cancer in a case-control study of women

Abstract

Poster Presentations - Abstract 2626

Background: Often, lung cancer is diagnosed at later stages, resulting in a 15% 5-year survival rate. Improved survival is seen for those with early stage disease, thus it is crucial to identify genetic markers that can identify those at the highest risk for early disease. In this study, we focused on understanding the risk of developing non-small cell lung cancer (NSCLC) associated with germline single nucleotide polymorphisms (SNPs) in apoptosis related genes among women in the Detroit metropolitan area. Methods: 453 cases of NSCLC and 478 control subjects were examined in a population based case-control study. Since the allele frequency differed significantly in over 74% of the SNPs between whites and African Americans, analysis was stratified by race. Eight SNPs found not to be in HWE were excluded from the study, leaving 97 SNPs in 32 apoptosis related genes examined for association with risk of lung cancer. Odds ratios and 95% confidence intervals were estimated from unconditional logistic regression models using 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: Among whites, a polymorphism in APAF-1 (rs1007573) was associated with a 2.86 fold increase in risk of lung cancer among smokers (95% CI: 1.58-5.16). SNPS in CD40 rs3765459 and rs1535045 were associated with a reduced risk of lung cancer among white smokers. After carrying out a backwards elimination procedure, only APAF-1 rs1007573 and CD40 rs1535045 remained as significant predictors of risk. Both of these SNPs were found to be noteworthy, as per the False Discovery Reporting Percentage (FDRP) method. In African Americans, 7 SNPs were found to be significantly associated with NSCLC. After the backwards elimination procedure, only SNPs in ATM rs1801516 (OR=24.15, 95% CI: 3.50-166.55), TNF rs1800629 (OR= 0.42, 95% CI: 0.18-0.99) and p63 rs6790167 (OR: 2.85, 95% CI:1.33-6.09) were found to be significant. Testing these SNPs using the FDRP method revealed that only p63 (rs6790167) was noteworthy. Indeed, this locus may represent an important target in NSCLC, as previous SNPs in p63 have been reported to increase the risk of lung cancer in larger GWAS studies. Conclusions: We report two significant SNPs associated with NSCLC risk in whites (APAF-1 rs1007573 and CD40 rs1535045) and one significant SNP in African Americans (p63 rs6790167) as potentially important contributors to NSCLC.