Role of Genetic Variations inCDK2,CCNE1andp27^KIP1in Prostate Cancer

Abstract

Background/Aim: Our aim was to investigate possible influences of genetic variants in genes involved in the G 1 /S transition , cyclin E1 (CCNE1) and cyclin-dependent kinase inhibitor 1B (p27 KIP1 )] on the expression/activity of their corresponding proteins and to assess the functional impact of these variants on the risk of prostate cancer. Materials and Methods: We genotyped 530 cases and 562 healthy controls for two relevant single nucleotide polymorphisms (CDK2 rs2069408 and CCNE1 rs997669) by TaqMan genotyping assay. p27 KIP1 rs2066827 polymorphisms were studied by polymerase chain reactionrestriction fragment length polymorphism assay. In addition, the expression of CDK2, CCNE1 and p27 KIP1 was evaluated by quantitative real-time-polymerase chain reaction and western blotting in 44 prostate cancer tissues and 31 benign prostatic hyperplasia tissues. Results: No association was found between CDK2 rs2069408, CCNE1 rs997669 or p27 KIP1 rs2066827 polymorphisms and an increased risk of prostate cancer development. Higher CDK2 expression was more prevalent in those with rs2069408 GG genotype than in AA carriers (p>0.05). We also noted reduced p27 KIP1 protein expression in those with the p27 KIP1 G109 allele. No difference was observed for CCNE1 expression in relation to the risky genotype (CC). A significant association was detected between CCNE1 mRNA overexpression and development of higher-grade carcinomas (Gleason score >7, p<0.05). Conclusion: Polymorphisms CDK2 rs2069408, CCNE1 rs997669 and p27 KIP1 rs2066827 have no significant impact on prostate cancer risk nor on the gene and protein expression of CDK2, CCNE1 and p27 KIP1 , although high CCNE1 expression was significantly associated with a higher tumour grade in patients with prostate cancer.

Polymorphisms in the gene encoding CYP1A2 influence prostate cancer risk and progression

“…The present case-control study was approved by the Ethical Board of Jessenius Faculty of Medicine, Comenius University (Martin, Slovak Republic) and conducted in accordance with The Declaration of Helsinki. Most of the subjects were also enrolled in our previous studies ( 26 , 27 ).…”