Challenges to association studies of prostate cancer

Although association studies have been performed successfully in many simple Mendelian diseases, this approach encounters some difficulty in complex diseases. As discussed above in relation to linkage analysis, one of the major problems is heterogeneity. Association studies are not only susceptible to etiological (genetic or environmental), inheritance (dominant, recessive or X-linked) and locus heterogeneity; they are also very sensitive to allelic (same gene but different mutations) and founder (same mutation exists in different genetic background) heterogeneity. Despite these difficulties, a large number of association studies have been reported.

To date, the bulk of reported association studies have focused on a straightforward design that compares genotype frequency among cases versus controls. However, it is unclear whether the traditional association approaches are likely to reveal hereditary prostate cancer genes. Rather, this approach may be more likely to reveal genes involved in prostate tumor progression. With regard to hereditary prostate cancer and the assessment of risk among unaffected men who may simply be presymptomatic, the most promising association studies focus on genes located within linkage regions, and include probands (the first individual ascertained) from HPC families, along with non-HPC cases and controls in the analyses.

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