No association between variant DNA repair genes and prostate cancer risk among men of African descent

Nicole A. Lavender, Oyeyemi O. Komolafe, Marnita Benford, Guy Brock, Jason H. Moore, Tiva T. VanCleave, J. Christopher States, Rick A. Kittles, La Creis R. Kidd

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

BACKGROUND. Recent reports hypothesize that multiple variant DNA repair gene interactions influence cancer susceptibility. However, studies identifying high-risk cancer-related genes use single gene approaches that lack the statistical rigor to model higher order interactions. METHODS. To address this issue,wesystematically evaluated individual and joint modifying effects of commonly studied polymorphic base and nucleotide excision repair genes relative to prostate cancer (PCA) risk using conventional logistic regression models and multifactor dimensionality reduction (MDR). We hypothesized that inheriting two or more compromised DNA repair loci may increase PCA risk due to altered gene product function. Six genetic alterations were evaluated using germ-line DNA samples from 208 PCA cases and 665 disease-free controls via Taq Man polymerase chain reaction. RESULTS. With the exception of XPD 312, no association existed between individual DNA repair single-nucleotide polymorphisms (SNPs) and PCA. Individuals with the XPD 312 Asn/ Asn genotype had an 8.6-fold increase in risk (OR=8.59; 95% CI=1.81-40.66). We did not observe any significant single gene or gene-gene interactions based on MDR modeling. CONCLUSIONS. Our findings emphasize the importance of utilizing a combination of traditional and advanced statistical tools to identify and validate single gene and multilocus interactions in relation to cancer susceptibility.

Original languageEnglish (US)
Pages (from-to)113-119
Number of pages7
JournalProstate
Volume70
Issue number2
DOIs
StatePublished - Feb 1 2010
Externally publishedYes

Keywords

  • Base excision repair
  • Gene-gene interactions
  • Logistic regression analysis
  • Multifactor dimensionality reduction
  • Nucleotide excision repair
  • Prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Urology

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    Lavender, N. A., Komolafe, O. O., Benford, M., Brock, G., Moore, J. H., VanCleave, T. T., States, J. C., Kittles, R. A., & Kidd, L. C. R. (2010). No association between variant DNA repair genes and prostate cancer risk among men of African descent. Prostate, 70(2), 113-119. https://doi.org/10.1002/pros.21048