Premium
No association between variant DNA repair genes and prostate cancer risk among men of African descent
Author(s) -
Lavender Nicole A.,
Komolafe Oyeyemi O.,
Benford Marnita,
Brock Guy,
Moore Jason H.,
VanCleave Tiva T.,
States J. Christopher,
Kittles Rick A.,
Kidd La Creis R.
Publication year - 2009
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.21048
Subject(s) - single nucleotide polymorphism , prostate cancer , multifactor dimensionality reduction , dna repair , gene , biology , genetics , genotype , cancer , bioinformatics , medicine
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, we systematically 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 TaqMan 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. Prostate 70: 113–119, 2010. ©2009 Wiley‐Liss, Inc.