BMC Cancer 2009, 9:397 http://www.biomedcentral.com/1471-2407/9/397 sons and spurious risk estimates by using a cross validation and permutation testing scheme as a built-in feature. Misclassification by case status is also a potential limitation for this study. There is a slight possibility that some of the controls with PSA less than 4 ng/ml may actu- ally have prostate cancer that remains undetected. Con- trols who had an abnormal PSA (>4.0 ng/ml) and/or irregular DRE underwent multiple core needle biopsies. Patients with an abnormal biopsy were reclassified as cases. Participants with a PSA (i.e., ≤ 4.0 ng/ml) but an abnormal DRE were excluded abnormal DRE were excluded from participating in the current study. These individuals were excluded because we could not predict with any level of certainty whether these individuals would develop prostate cancer. We also excluded individ- uals who were: (1) diagnosed with BPH following a biopsy; or (2) had an abnormal PSA and/or an irregular DRE. Since one cannot predict with any level of certainty whether individuals diagnosed with BPH would develop prostate cancer, these individuals were excluded from the current study. As implied within Lobe et al., 2006, even after close inspection of prostate cancer tissue, it is possi- ble to miss a microscopic nodule that can later develop into cancer[55]. If controls in our study population were still misclassified after undergoing a PSA test, DRE, and/or multiple core needle biopsies, then we may expect our cal- culated risk estimates to underestimate the relationship between the selected GST polymorphisms and prostate cancer susceptibility. But this issue plaques all cancer epi- demiology studies. Unfortunately, it is impractical to sub- ject all patients to a radical prostatectomy to permit an extensive evaluation and more accurate classification of case status. Another challenge for genetic epidemiology studies involving study participants of African descent is their unique population history of gene flow from divergent populations[56,57]. The current study adjusted single loci models for genetic heterogeneity (i.e., population admix- ture). This also helps to circumvent misclassification of study participants related to self-identified race/ethnicity (SIRE). Our findings suggest that inclusion of WAA did not significantly change the risk estimates relative to unadjusted models; if anything it makes them more pre- cise. Also, this study may be limited due to lack of consid- eration of the genetic heterogeneity of selected targets. This could be the reason we did not observe any statistical significant effects among GST polymorphisms and smok- ing interactions in relation to PCA risk (p = 0.105). Conclusion In summary, our findings indicate a moderately signifi- cant association between risk and among men possessing at least one variant GSTP1 105 Val allele (p = 0.049) among men of African descent. MDR analysis validated the logistic regression findings and identified the GSTP1105 Val allele (p = 0.001) as the best single factor model for predicting PCA risk. The ability of MDR to eval- uate main effects and remain effective with relatively small sample sizes of at least 200 cases and 200 controls strengthens the power of this study. Statistically signifi- cant single and multi-locus models maybe adjusted for potential confounders by placing the MDR output varia- bles into a LR model. Furthermore, this study is robust since it utilizes multiple statistical analysis tools to exam- ine the single gene as well as gene-gene or gene-cigarette smoking combination effects in relation to PCA risk. Competing interests The authors declare that they have no competing interests. Authors' contributions NAL, MLB, TTV and LRK designed and carried out geno- typing assays and analyses; NAL, GNB, JHM and LRK per- formed statistical analyses; GNB, JHM, DWH and LRK served as mentors in designing and carrying out this project and editing the manuscript; All authors reviewed and edited the manuscript. All authors accepted the final manuscript. Acknowledgements The authors thank the men of African descent for their participation in the current study. This work was supported by the National Cancer Institute R03 CA128028 grant and the National Institute of Environmental Health Sciences T32 ES011564 and P30-ES014443 grants. 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