NAT2 and NER genetic variants and sporadic prostate cancer susceptibility in African Americans

S. Hooker, C. Bonilla, F. Akereyeni, C. Ahaghotu, R. A. Kittles

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Prostate cancer is a common malignancy that disproportionately affects African-American men. Environmental factors and variation in genes responsible for chemical and dietary carcinogen metabolism and DNA damage repair may modulate risk. Fourteen single nucleotide polymorphisms in NAT2 and four NER genes (ERCC1, XPF/ERCC4, XPG/ERCC5 and CSB/ERCC6) were genotyped in a case-control study of 254 African-American prostate cancer cases and 301 healthy controls from Washington, DC. Smoking status, BMI, age and genetic ancestry were included as covariates in the association analyses. We found that individuals homozygous for the XPG/ERCC5 -72C/T promoter polymorphism had a significant reduction in risk, for prostate cancer (OR=0.12; 95% CI = 0.03-0.48). A haplotype trend regression test also revealed a protective effect for the haplotype bearing the T allele (P = 0.003). In silica analyses suggest a functional implication for the promoter variant since it deletes a GCF transcriptional factor-binding site responsible for the downregulation of transcription. The protective effect of the promoter SNP on risk for prostate cancer was independent of smoking. In contrast, none of the SNPs typed for NAT2, ERCC1, ERCC4 and ERCC6 showed significant association with risk. Additional tests for genotype interactions were not significant. We note that there may be other factors, such as dietary exposures, which may modulate prostate cancer risk in combination with genetic variation within the NAT2 and NER genes. Our results, in combination with previous observations of LOH for ERCC5 in prostate tumors, provide further evidence for a role of XPG/ ERCC5 in the etiology of prostate cancer.

Original languageEnglish (US)
Pages (from-to)349-356
Number of pages8
JournalProstate Cancer and Prostatic Diseases
Volume11
Issue number4
DOIs
StatePublished - Nov 21 2008
Externally publishedYes

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ASJC Scopus subject areas

  • Oncology
  • Urology
  • Cancer Research

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