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

Abstract

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. 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. 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. Our findings emphasize the importance of utilizing a combination of traditional and advanced statistical tools to identify and validate single gene and multi-locus interactions in relation to cancer susceptibility.

Association between APE1 T1349G polymorphism and prostate cancer risk: evidence from a meta-analysis

“…The associations between APE1 T1349G polymorphism and risk of other types of cancers have not been fully assessed in currently available studies [21][22][23][24]. In addition, studies on the association between APE1 T1349G polymorphism and risk of prostate cancer remained inconclusive [7,10,[13][14][15][16]. Therefore, we performed this present meta-analysis to precisely assess the association between APE1 T1349G polymorphism and prostate cancer risk.…”

“…In addition, those seven studies contained a total of 3,063 individuals [7,10,[13][14][15][16]. Among those seven studies, three studies were from Asian population, two were from Caucasians, and the other two were from Africans [7,10,[13][14][15][16]. The main characteristics of seven studies included into the meta-analysis were shown in Table 1.…”

“…Finally, seven studies from six publications were finally included into the meta-analysis [7,10,[13][14][15][16]. In addition, those seven studies contained a total of 3,063 individuals [7,10,[13][14][15][16]. Among those seven studies, three studies were from Asian population, two were from Caucasians, and the other two were from Africans [7,10,[13][14][15][16].…”

“…After screening the titles and abstracts of those 29 studies, 23 studies were further excluded for duplicate data, reviews, or non-relevant research studies. Finally, seven studies from six publications were finally included into the meta-analysis [7,10,[13][14][15][16]. In addition, those seven studies contained a total of 3,063 individuals [7,10,[13][14][15][16].…”

“…Previous studies have shown that there are many single nucleotide polymorphisms in the APE1 gene, and the most frequently studied one is APE1 T1349G polymorphism (rs1130409) [11,12]. APE1 T1349G polymorphism was considered to be associated with risk of cancer, but studies on the association between APE1 T1349G polymorphism and risk of prostate cancer remained inconclusive [7,10,[13][14][15][16]. In order to shed some light on these inconsistent findings, a meta-analysis was performed to precisely assess the association between APE1 T1349G polymorphism and prostate cancer risk.…”