Apoptosis is an essential physiological process that regulates cellular proliferation. Here, we explored the effect of DNA sequence variation within the BCL-2 gene on prostate cancer susceptibility in three clinical populations, consisting of 428 African Americans, 214 Jamaicans and 218 European Americans. We observed a 70% reduced risk for prostate cancer among the European Americans who had possessed two copies of a promoter variant À938C/A. Additionally, common BCL-2 haplotypes appeared to influence prostate cancer risk; however, studies in larger data sets are needed to confirm our findings. Our data suggest that inherited BCL-2 variants may be associated with a decrease in prostate cancer susceptibility.

Prostate cancer (PCA) detection could be improved by identifying genetic susceptibility markers within essential biological pathways. The goal of this study is to identify an important panel of genetic susceptibility markers. This study evaluates the interaction between two variant genes (NAT1 and MDR1) in relation to PCA risk using a case‐control study of 918 African American men. Individuals who have at least one rapid activation NAT1*10 combined with one or more MDR1 3435T alleles (linked with reduced xenobiotic‐cellular extrusion) were hypothesized to have an elevated risk of PCA relative to those with low risk genotypes. Genetic alterations detected in germ‐line DNA collected from 220 incident PCA cases and 698 healthy age matched controls were assessed using TaqMan real‐time polymerase chain reaction. For the first time to our knowledge, the complex interaction among highly variant pharmacokinetic genes and their combined modifying effects on PCA risk were evaluated using a computationally savvy methodology that compliments logistic regression models with multifactor dimensionality reduction. The high‐risk NAT1*10 combined with high risk MDR1 alleles did not modify PCA risk (OR = 1.07;95%CI = 0.53–2.14, P=0.58). Future studies will expand our current efforts by considering other biological pathways important in PCA tumorigenesis using advanced biostatistical tools. Bales Medical Research Fund

Prostate cancer (PCA) detection could be improved by identifying genetic susceptibility markers within essential biological pathways. This study evaluated the individual and joint modifying effects of 2 highly variant genes (MDR1 and XPD) in relation to PCA risk within a large and unique case‐control study. We hypothesize men possessing two or more high‐risk XPD 312Asn alone or combined with MDR1 3435T alleles have an increased risk of developing PCA, due to decreased capacity to repair DNA damage or eliminate exogenous compounds. Genetic alterations detected in germ‐line DNA collected from 220 incident PCA cases and 698 healthy age matched controls were assessed using TaqMan real‐time PCR. Gene‐gene interaction was analyzed by LR analysis models. A 1.4‐6‐fold increase was observed in PCA risk among carriers with 1 or more high‐risk XPD 312Asn alleles alone or combined with at least one slow MDR1 3435T alleles. This study showed variant XPD alone or combined with polymorphic MDR1 modify PCA susceptibility among AA men. Future studies will evaluate an important panel of genetic susceptibility biomarkers for detection within high‐risk populations. Bales Medical Research Fund

DNA damage induced by reactive oxygen species may be repaired by a complex network of base excision repair (BER) enzymes. BER enzymes (hOGG1, APE1 and XRCC1) are involved in sequential reactions that recognize and repair the damage resulting from oxidative stress. This study evaluated the individual and joint modifying effects of three highly variant BER genes in relation to prostate cancer risk within a large and unique prostate cancer case‐control study of 918 African‐American (AA) men. We hypothesize individuals who possess at least one variant hOGG1 326Cys allele in combination with one or more variant BER alleles (APE1 148Glu, XRCC1 399Glu) will have an increased prostate cancer risk, presumably due to reduced DNA repair capacity. Genetic alterations detected in germ‐line DNA collected from 220 incident PCA cases and 698 healthy age matched controls were assessed using TaqMan real‐time polymerase chain reaction. The intricate gene‐gene interaction was analyzed using logistic regression analysis models, adjusted for age and PSA levels. We did not observe a significant role for individual BER high‐risk alleles alone (P ≥ 0.215) or combined (P ≥ 0.509) in relation to prostate cancer risk among AA men. To expand our current efforts, future studies will consider the complex genetic architecture of prostate cancer, involving additional BER genes (e.g., XRCC3, XRCC4, MBD4, UNG). Bales Medical Research Fund