| Objective To clarify the etiological effect of three SNPs on PCa, including CCND1 A870G,TNF-αG-308A and TNF-αG-238A, a sample size of 245 cases-controls pairs is included in this study.Materials and Methods Two hundred and fourty-five cases of PCa and 245 sex-, age-matched controls were recruited. The genotypes of CCND1 A870G,TNF-αG-308A and TNF-αG-238A were determined by a PCR based TaqMan method.Odds radios (ORs) for PCa and 95% confidence intervals (CIs) from unconditional logistic regression models were used to evaluate relative risks. In the multivariate analyses, age were included in the logistic regression models as covariates. A P value of < 0.05 was considered significant. All above analyses were performed using SPSS 10.0 software (SPSS, Chicago, IL). Hardy-Weinberg equilibrium tests were performed using website-based software at http://ihg.gsf.de/ihg/snps.html. Genetic linkage analysis were performed using Haploview (3.1.1) software. Haplotype analysis were performed using the Phase(2.1) software.Results 1. The G allele of CCND1 A870G was marginally significantly associated with the presence of PCa and had a 1.31-fold increased risk of PCa (95% CI 1.00-1.72,P = 0.054) compared to the A allele. Compared to AA homozygote, AG heterozygote had a 1.43-fold increased risk (95% CI = 0.89～2.31, P = 0.142), whereas GG homozygote had a higher 2.02-fold increased risk (95% CI = 1.07～3.80,P = 0.029)of PCa (Armitage's trend test, P = 0.029). The CCND1 870G genotypes (AG or GG) is significantly associated with the presence of metastasis of PCa(P = 0.014).2. There was no overall significant correlation between PCa and TNF-αG-308A, although an decreased risk of PCa was observed among GA heterozygotes (OR = 0.77,P = 0.275) or AA homozygotes (OR = 0.92,P = 0.933) compared to GG homozygotes.3. The A allele of TNF-αG-238A confered a significantly decreased risk for PCa (OR = 0.43, 95% CI = 0.20～0.93,P = 0.031)when compared to the G allele. Compared to GG homozygote, GA heterozygote had a 0.42-fold decreased risk of PCa (95% CI = 0.19～0.91,P = 0.027). No AA homozygote was found in this population.4. The G-308A and G-238A polymorphisms in TNF-αgene were completely linked (D'=1.0). When compared with G_G(-308G_-238G)haplotype, the ORs of PCa for A_G haplotype was 0.78 (95% CI = 0.51～1.19,P = 0.250), for G_A haplotype was 0.42 (95% CI = 0.20～0.90,P = 0.026), and for both (A_G or G_A haplotype) was 0.67(95% CI = 0.46～0.98,P = 0.040).5. Compared to GG/GG(-308G_-238G/-308G_-238G)diplotype, GG/GA diplotype had a 0.37-fold decreased risk (95% CI = 0.17～0.84,P = 0.017), whereas all diplotypes except for GG/GG had a 0.62-fold decreased risk (95% CI = 0.41～0.94,P = 0.024)of PCa.Conclusions The G allele of the CCND1 A870G conferred a risk effect for PCa, with a dose-dependent effect. The findings suggests that CCND1 A870G is one of the genetic risk factors for PCa.The TNF-αG-308A was not an independent protective factor for PCa, although a decrease risk effect was observed. The A allele of TNF-α-238A was associated with the decreased risk of PCa and is potentially one of the independently genetic protective factors for PCa in this population of China. The G-308A and G-238A in TNF-αgene have a synergetic protective effect for PCa.All SNPs in this study occurs at a minimal allele frequency of >1% in Chinese population, and thus can be considered validation polymorphism. |
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