RT Journal Article
SR Electronic
T1 Role of Genetic Variations in <em>CDK2</em>, <em>CCNE1</em> and <em>p27<sup>KIP1</sup></em> in Prostate Cancer
JF Cancer Genomics - Proteomics
JO Cancer Genomics Proteomics
FD International Institute of Anticancer Research
SP 362
OP 371
DO 10.21873/cgp.20326
VO 19
IS 3
A1 MÁRK HÍVEŠ
A1 JANA JUREČEKOVÁ
A1 JÁN KLIMENT
A1 MARIÁN GRENDÁR
A1 PETER KAPLÁN
A1 RÓBERT DUŠENKA
A1 DANIEL EVIN
A1 MARTA VILČKOVÁ
A1 KLAUDIA HÍVEŠ HOLEČKOVÁ
A1 MONIKA KMEŤOVÁ SIVOŇOVÁ
YR 2022
UL http://cgp.iiarjournals.org/content/19/3/362.abstract
AB Background/Aim: Our aim was to investigate possible influences of genetic variants in genes involved in the G1/S transition [cyclin-dependent kinase-2 (CDK2), cyclin E1 (CCNE1) and cyclin-dependent kinase inhibitor 1B (p27KIP1)] 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. p27KIP1 rs2066827 polymorphisms were studied by polymerase chain reaction-restriction fragment length polymorphism assay. In addition, the expression of CDK2, CCNE1 and p27KIP1 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 p27KIP1 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&gt;0.05). We also noted reduced p27KIP1 protein expression in those with the p27KIP1 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 &gt;7, p&lt;0.05). Conclusion: Polymorphisms CDK2 rs2069408, CCNE1 rs997669 and p27KIP1 rs2066827 have no significant impact on prostate cancer risk nor on the gene and protein expression of CDK2, CCNE1 and p27KIP1, although high CCNE1 expression was significantly associated with a higher tumour grade in patients with prostate cancer.