BMC Cancer 2009, 9:397 http://www.biomedcentral.com/1471-2407/9/397 and a 1000-fold permutation testing p-value of 0.001 (Table 3). Upon evaluation of gene-gene combination effects, LR modeling revealed a 2.1-fold increase in PCA risk associated with men possessing the GSTP1 (Val/Val) and GSTM1 (*1/*1 + *1/*0) alleles (OR = 2.11; 95%CI = 1.07-4.16; p-value for interaction = 0.062). Initially, it appeared as though this interaction was a significant PCA predictor following MDR analysis with a statistically sig- nificant 1000-fold permutation testing p-value of 0.01. However, this gene combination effect was primarily driven by the GSTP1 loci attributed to the lack of addi- tional information gain comparing the GSTM1-GSTP1 axis (IG = 0.04%) to either GSTP1 or GSTM1 loci alone (IG = 0.58% and 0.03%, respectively) (Figure 1). Lastly, no significant risk effects were detected among the GST deletion polymorphisms (p = 0.622) or the GSTP1-GSTP1 and GSTM1-GSTT1 combinations (p = 0.557 and 0.814, respectively). For our exploratory analysis of gene-envi- ronment interactions associated with risk, LR modeling indicated that smoking status did not modify the relation- ship between the GST SNPs and PCA risk (p for interac- tion ≥ 0.135), as shown in Table 4. Discussion Previous studies suggest that oxidative stress and reactive species are becoming increasingly important in prostate carcinogenesis[4,11,12,42-45]. If these electrophilic com- pounds are not removed or reduced to less active forms, they may result in damage to biomolecules (e.g., DNA, proteins, etc.) and ultimately lead to cellular dysfunction or transformation. Consequently, the role of antioxidant enzymes has been commonly investigated in relation to PCA development because of their function in the detoxi- fication of potentially damaging carcinogens and/or reac- tive oxygen species (ROS)[4,46-48]. The GSTs in particular have been extensively studied since they are able to conjugate a wide range of oxidative sub- strates[6,11,43,49,50]. Variations within these genes can cause a loss or reduction in enzymatic activity and have been associated with increased risk of prostate as well as several other cancers (e.g., colon, breast, and lung)[6,12,51-53]. In the case of PCA, reports have observed that PCA cases possess lower antioxidant enzyme levels in prostate tis- sues compared to both healthy controls and men with benign prostatic hyperplasia (BPH)[48]. In addition, PCA tissues appear to contain higher amounts of ROS and oxi- dative DNA damage [46-48]. Some investigators speculate these effects may be attributed to GST genetic polymor- phisms (i.e., GSTM1*0/*0, GSTT1*0/*0, and GSTP1 Val) linked with compromised oxidative repair capac- ity[5,12,26,41,43,54]. The goal of this study was to evalu- ate GSTM1 and GSTT1 gene deletions, variant GSTP1 105 Val, and cigarette smoking as predictors of PCA risk among 873 men of African descent (208 cases and 665 controls). We hypothesized that individuals who possess one or more genotypes associated with reduced detoxifi- IFnitgeurarceti1on entropy model for GST gene variations and prostate cancer risk Interaction entropy model for GST gene variations and prostate cancer risk. This graphical model, describes the percent entropy that is explained by each GST SNP or a combination of two loci within our study population. Positive percent entropy indicates information gain or synergy. However, negative percent indicates redundancy or lack of information gain. Schematic coloration used in the visualization tools represents a continuum from synergy (i.e. non-additive) to redundancy. The colors range from red representing a high degree of synergy (positive information gain), orange a lesser degree, and gold representing independence and a midway point between synergy and redundancy. On the other hand, green represents redun- dancy. Note that the gene combination effect is primarily driven by the GSTP1 loci attributed to the lack of additional informa- tion gain comparing the GSTM1-GSTP1 axis (IG = 0.04%) to either GSTP1 or GSTM1 loci alone (IG = 0.58% and 0.03%, respectively) Page 6 of 10 (page number not for citation purposes)