p27-V109G Polymorphism Is Not Associated with the Risk of Prostate Cancer: A Case-Control Study of Han Chinese Men in Central China

Abstract

Objective We conducted an update meta-analysis aiming to verify the association between p27-V109G polymorphism and cancer risk, particular for prostate cancer (PCa). Then, we conducted a case-control study of Han Chinese in central China to verify the evidence-based results. Methods Relevant studies were collected from diverse databases up to March 2017. In addition, a hospital-based (H-B) case-control study enrolling 90 PCa patients and 140 healthy controls was included to verify these evidence-based findings. Genetic risk was calculated by odds ratio (OR) with its corresponding 95% confidence interval (CI). The p27-V109G polymorphism was determined by MassARRAY genotyping method. Results Finally, twenty-four published studies comprising 9627 cases and 12,102 controls were enrolled for the current meta-analysis. Overall analysis suggested that p27-V109G polymorphism decreased overall cancer risk in allelic contrast, heterozygote, and dominant models. When stratified analysis was conducted by ethnicity, data revealed that p27-V109G polymorphism was associated with a decreased cancer risk in Caucasians. Highlighted in the subgroup analysis by cancer type, we uncovered a significantly decreased risk of PCa in allelic contrast, dominant, homogeneous, and recessive models. However, in the validation case-control study, we failed to uncover a positive association between p27-V109G polymorphism and PCa risk. In addition, negative results were also identified when subgroup analyses were stratified by age, tumor grade, tumor stage, PSA levels, and other measurements. Conclusion Although evidence-based results suggest that p27-V109G polymorphism plays a protective role in overall cancer risk, particularly for PCa, our case-control study failed to validate any association between this particular polymorphism and PCa risk.

Role of Genetic Variations inCDK2,CCNE1andp27KIP1in Prostate Cancer

“…One case-control study demonstrated that p27 KIP1 rs2066827 polymorphism is associated with an increased risk of prostate cancer (31), whereas another study and a meta-analysis suggested that this polymorphism is associated with a reduced risk of prostate cancer (13,17). In addition, other studies have reported no association between the p27 KIP1 rs2066827 polymorphism and prostate cancer risk (30,32,33), which our results are in agreement with. Several possible causes can be proposed related to the inconsistency between our study and the other investigations, such as sample sizes and heterogeneous populations/ethnic variance.…”

“…We observed no significantly increased risk of prostate cancer for CDK2 rs2069408 and CCNE1 rs997669 mutant genotypes by all clinicopathological parameters. Furthermore, our data do not suggest that the p27 KIP1 rs2066827 polymorphism is associated with PSA level, Gleason score or pathological T stage, thus confirming the overall null association with the clinicopathological characteristics of prostate cancer, as reported previously (32,33). Interestingly, we did find that CCNE1 mRNA expression was significantly increased in carcinomas with Gleason scores higher than 7.…”

“…Zhu et al, using Polyphen2 bioinformatics tools, to show that the p27 KIP1 rs2066827 polymorphism is predicted to be benign and will not affect the protein function of p27 KIP1 (30). During the past few years, several studies have focused on the effects of p27 KIP1 rs2066827 polymorphism on prostate cancer risk within various ethnic populations (13,17,(31)(32)(33). In the literature, both the T and G alleles of p27 KIP1 rs2066827 have been shown to be associated with risk of but also protection against malignancy.…”

CDKN1B Val 109 Gly variant is not related to risk of prostate cancer

“…Nevertheless, another group failed to validate any correlation between this variant and susceptibility of PCa. 27 Previous meta-analysis showed evidence that the G allele of CDKN1B was correlated with a decreased risk of PCa under the dominant genetic model (OR = 0.60, 95% CI = 0.36-0.98, P = .04). 23 In the present analysis, continually appeared case-control studies were screened and more information about this CDKN1B polymorphism was identified.…”

“…They also observed that cells transfected with G‐allele showed a lower proliferative activity and expression level of p27 protein than cells transfected with V‐allele. Nevertheless, another group failed to validate any correlation between this variant and susceptibility of PCa . Previous meta‐analysis showed evidence that the G allele of CDKN1B was correlated with a decreased risk of PCa under the dominant genetic model (OR = 0.60, 95% CI = 0.36‐0.98, P = .04) .…”