Variant Base Excision Repair Genes (hOGG1, APE1, XRCC1) and Prostate Cancer Risk in African‐American Men

Abstract

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