ABSTRACT
OBJECTIVE: We evaluated the individual and combination effects of NAT1, NAT2 and tobacco smoking in a case-control study of 219 incident prostate cancer (PCa) cases and 555 disease-free men. METHODS: Allelic discriminations for 15 NAT1 and NAT2 loci were detected in germ-line DNA samples using TaqMan polymerase chain reaction (PCR) assays. Single gene, gene-gene and gene-smoking interactions were analyzed using logistic regression models and multi-factor dimensionality reduction (MDR) adjusted for age and subpopulation stratification. MDR involves a rigorous algorithm that has ample statistical power to assess and visualize gene-gene and gene-environment interactions using relatively small samples sizes (i.e., 200 cases and 200 controls). RESULTS: Despite the relatively high prevalence of NAT1*10/*10 (40.1%), NAT2 slow (30.6%), and NAT2 very slow acetylator genotypes (10.1%) among our study participants, these putative risk factors did not individually or jointly increase PCa risk among all subjects or a subset analysis restricted to tobacco smokers. CONCLUSION: Our data do not support the use of N-acetyltransferase genetic susceptibilities as PCa risk factors among men of African descent; however, subsequent studies in larger sample populations are needed to confirm this finding.
ABSTRACT
Animal and in vitro models of prostate cancer demonstrate high IL-10 levels result in smaller tumors, fewer metastases, and reduced angiogenesis compared to controls. We sought to examine the hypothesis that genotypes correlated with low IL-10 production may be associated with increased prostate cancer risk among Finnish male participants from the Alpha-tocopherol Beta-carotene Cancer Prevention Study. DNA from 584 prostate cancer cases and 584 controls was genotyped for four IL-10 alleles, -1082, -819, -592, and 210. DNA from more of the controls than cases failed to amplify, resulting in 509 cases and 382 controls with genotype data for -1082; 507 and 384 for -819; 511 and 386 for -592; and 491 and 362 for 210. Odds ratios for the association between the IL-10 genotypes and risk of prostate cancer or, among cases only, high-grade disease were calculated using logistic regression. In this population, the -819 TT and -592 AA low expression genotypes were highly correlated. These two genotypes also were associated with increased prostate cancer susceptibility (OR = 1.92, 95% CI 1.07-3.43 for -819) and, among cases, with high-grade tumors (OR = 2.56, 95% CI 1.26-5.20 for -819). These data demonstrate genotypes correlated with low IL-10 production are associated with increased risk of prostate cancer and with high-grade disease in this population.
