No association between variant DNA repair genes and prostate cancer risk among men of African descent.
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.
Lavender
Nicole A
NA
Department of Pharmacology & Toxicology, School of Medicine, University of Louisville, Louisville, Kentucky 40202, USA.
Komolafe
Oyeyemi O
OO
Benford
Marnita
M
Brock
Guy
G
Moore
Jason H
JH
Vancleave
Tiva T
TT
States
J Christopher
JC
Kittles
Rick A
RA
Kidd
La Creis R
LC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044383:Black People; D016022:Case-Control Studies; D004260:DNA Repair / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000235:genetics*; D012307:Risk Factors