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Prostate cancer susceptibility genes on 8p21-23 in a Dutch population
M P Zeegers1, D Nekeman, H S Khan
1Unit of Urologic and Genetic Epidemiology, Department of Public Health, Epidemiology and Biostatistics, School of Health and Population Sciences, University of Birmingham, Birmingham, UK.
Background:
Prostate cancer is the most commonly diagnosed cancer in men in Europe and the United States. Numerous studies have indicated genetics to have a major role in the aetiology of this disease; as much as 42% of the risk may be explained by heritable factors. Genome-wide association studies have detected an association between prostate cancer and chromosome 8p21-23. In this study, we analysed eight microsatellite (MS) markers in that region in order to confirm previous results and narrow down the location of candidate prostate cancer genes.
Methods:
292 cases and 278 controls were selected from the Netherlands Cohort Study (NLCS). The following MSs were used in the analyses: D8S136, D8S1734, D8S1742, D8S261, D8S262, D8S351, D8S511 and D8S520. Associations were evaluated using a χ(2) test and logistic regression. We checked for any effects on the association by tumour stage.
Results:
Associations that were found confirmed previous research that pointed to the 8p21-23 region. Two MSs: D8S136 (odds ratio (OR), 0.69; P=4.00 × 10(-28)), and D8S520 (OR, 0.80; P=3.37 × 10(-11)), were consistently and strongly related with prostate cancer. Genotype analysis showed an additive effect for D8S136 (P-trend=6.22 × 10(-03)) and D8S520 (P-trend=2.62 × 10(-22)), suggesting an increased risk for people with a short number of repeats on both alleles at those markers.
Conclusions:
This study provides strong evidence that the 8p21-23 region is likely to harbour prostate cancer genes.
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