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Therefore, we hypothesized that polymorphisms of genes encoded cyclin-dependent kinase 4 and 6 (CDK4 and CDK6), cyclin D1 (CCND1), CDK inhibitors p16\n INK4a<\/jats:sup>\n and p15\n INK4b<\/jats:sup>\n , as well as the retinoblastoma protein (RB), could modulate prostate cancer risk and influence the corresponding mRNA levels.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and results<\/jats:title>\n \n We evaluated\n CDK4<\/jats:italic>\n rs2069502,\n CDK6<\/jats:italic>\n rs2285332,\n CCND1<\/jats:italic>\n rs9344,\n p16<\/jats:italic>\n \n INK4a<\/jats:italic>\n <\/jats:sup>\n rs11515,\n p15<\/jats:italic>\n \n INK4b<\/jats:italic>\n <\/jats:sup>\n rs3217986, and\n RB<\/jats:italic>\n rs3092904 polymorphisms using TaqMan\n \u00ae<\/jats:sup>\n SNP Assays in a cohort comprising 532 prostate cancer patients and 567 control subjects. Additionally, we measured the relative mRNA expression levels of genes encoding these proteins in RNA derived from 44 prostate tumor tissues and 31 benign prostatic hyperplasia (BPH) tissues using quantitative real-time PCR (qRT-PCR). No statistically significant associations were found between the\n CDK4<\/jats:italic>\n rs2069502,\n p16<\/jats:italic>\n \n INK4a<\/jats:italic>\n <\/jats:sup>\n rs11515 and\n RB<\/jats:italic>\n rs3092904 polymorphisms and prostate cancer risk. However, the\n GA<\/jats:italic>\n genotype of\n CCND1<\/jats:italic>\n rs9344 polymorphism was significantly associated with an increased risk of prostate cancer (OR, 1.64; 95% CI, 1.23\u20132.20;\n p<\/jats:italic>\n \u2009<\u20090.001). Moreover, the relative mRNA expression levels of\n CCND1<\/jats:italic>\n ,\n p15<\/jats:italic>\n \n INK4b<\/jats:italic>\n <\/jats:sup>\n and\n RB<\/jats:italic>\n were significantly lower (\n p<\/jats:italic>\n <0.05) in prostate tumor tissues compared to BPH tissues. Furthermore, lower relative expression levels of\n CDK4<\/jats:italic>\n and\n p16<\/jats:italic>\n \n INK4a<\/jats:italic>\n <\/jats:sup>\n mRNA were associated with elevated serum PSA levels (\u226510 ng\/ml;\n p<\/jats:italic>\n <0.05), while reduced relative expression of\n p15<\/jats:italic>\n \n INK4b<\/jats:italic>\n <\/jats:sup>\n was correlated with a higher pathological T stage (pT3\/pT4;\n p<\/jats:italic>\n <0.05).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Our findings indicate that genetic alterations, including polymorphisms and\/or gene expression changes in the cyclin D1-CDK4-p16\n INK4a<\/jats:sup>\n \/p15\n INK4b<\/jats:sup>\n -RB pathway, are associated with prostate cancer risk.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1007\/s11033-025-10531-1","type":"journal-article","created":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T22:05:13Z","timestamp":1746050713000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Genetic alterations of Cyclin D-CDK4\/6-INK4-RB pathway in prostate cancer"],"prefix":"10.1007","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6467-9409","authenticated-orcid":false,"given":"Monika Kme\u0165ov\u00e1","family":"Sivo\u0148ov\u00e1","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00e1rk","family":"H\u00edve\u0161","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00e1n","family":"Kliment","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R\u00f3bert","family":"Du\u0161enka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mari\u00e1n","family":"Grend\u00e1r","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Evin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Kapl\u00e1n","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina Kno\u0161ko","family":"Bro\u017eov\u00e1","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Vil\u010dkov\u00e1","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrej","family":"Vondr\u00e1k","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1743-5137","authenticated-orcid":false,"given":"Jana","family":"Jure\u010dekov\u00e1","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,4,30]]},"reference":[{"key":"10531_CR1","doi-asserted-by":"publisher","unstructured":"Schatten H (2018) Brief Overview of Prostate Cancer Statistics, Grading, Diagnosis and Treatment Strategies. 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