Single Nucleotide Polymorphisms in Selected Apoptotic Genes and BPDE-Induced Apoptotic Capacity in Apparently Normal Primary Lymphocytes: A Genotype-Phenotype Correlation Analysis. (15th October 2008)

• Record Type: Journal Article
• Authors: Hu, Zhibin; Li, Chunying; Chen, Kexin; Wang, Li-E; Sturgis, Erich M.; Spitz, Margaret R.; Wei, Qingyi
• Other Names: Vineis Paolo Academic Editor.
• Is Part Of: Journal of cancer epidemiology. Volume 2008(2008)
• Publication Date: 2008-10-15
• Subjects: Cancer -- Epidemiology -- Periodicals; 616.994005
• DOI: 10.1155/2008/147905
• Languages: English
• ISSNs: 1687-8558

Abstract

Abstract : Apoptotic capacity (AC) in primary lymphocytes may be a marker for cancer susceptibility, and functional single nucleotide polymorphisms (SNPs) in genes involved in apoptotic pathways may modulate cellular AC in response to DNA damage. To further examine the correlation between apoptotic genotypes and phenotype, we genotyped 14 published SNPs in 11 apoptosis-related genes (i.e., p53, Bcl-2, BAX, CASP9, DR4, Fas, FasL, CASP8, CASP10, CASP3, and CASP7 ) and assessed the AC in response to benzo[a]pyrene-7, 8-9, 10-diol epoxide (BPDE) in cultured primary lymphocytes from 172 cancer-free subjects. We found that among these 14 SNPs, R72P, intron 3 16-bp del/ins, and intron 6 G>A inp 53, −938C>A in Bcl-2, and I522L in CASP10 were significant predictors of the BPDE-induced lymphocytic AC in single-locus analysis. In the combined analysis of the threep 53 variants, we found that the individuals with the diplotypes carrying 0-1 copy of the commonp 53 R-del-G haplotype had higher AC values compared to other genotypes. Although the study size may not have the statistical power to detect the role of other SNPs in AC, our findings suggest that some SNPs in genes involved in the intrinsic apoptotic pathway may modulate lymphocytic AC in response to BPDE exposure in the general population. Larger studies are needed to validate these findings for further studying individual susceptibility to cancer and other apoptosis-related diseases.