p16(CDKN2) gene polymorphism: association with histologic subtypes of epithelial ovarian cancer in China

Abstract

p16 is an important tumor suppressor gene, which is inactivated in many kinds of tumors. The common variants of p16 may be associated with the risk of certain tumors development. We analyzed the frequency of two adjacent polymorphisms in p16 exon 3 (540C-->G and 580C-->T) and their haplotype in blood samples from epithelial ovarian cancer (EOC) patients and healthy controls using polymerase chain reaction-restriction fragment length polymorphism. The results showed that the genotype frequency of p16 580C-->T polymorphism was significantly different among histologic subtypes of EOC (P= 0.02). T allele carriers significantly reduced the risk of serous EOC; the adjusted odds ratio was 0.40 (95% CI = 0.19-0.84). There are neither association between p16 540C-->G polymorphism and EOC development, progression, nor association between the haplotypes of two single nucleotide polymorphisms and the tumor development. Our results suggested that the p16 580C-->T polymorphism might affect the individual susceptibility to specific subtypes of EOC. Different types of ovarian cancer might adopt distinct carcinogenetic pathways. However, this result may be further validated in a larger sample of patients.

Association between p16(CDKN2A) C540G polymorphism and tumor behavior in prolactinoma: A single-center study

“…(Table IV). Accordingly, a significantly higher frequency of the CG genotype and G allele was detected in the samples in comparison with certain previous reports (20,33,35,36). Subgroup comparisons for the tumor behavior of prolactinoma have also shown that those with a high Ki67 index and with giant prolactinomas had a higher frequency of CG genotype as compared with the other groups (although not statistically significant) in the study and when compared with previous studies.…”

“…The HRs (95% CIs) for one, two or three adverse genotypes were 2.13 (1.04-4.36), 3.18 (1.37-7.39) and 10.09 (3.17-32.05), respectively, and these findings indicate that polymorphisms in cell cycle genes may represent promising markers for patients with pancreatic cancer (34). Yan et al (20) observed no association between the p16 C540G polymorphism and early ovarian cancer and progression risk. Furthermore, no association between haplotypes of two different single-nucleotide polymorphisms and tumor progression has been found.…”

“…Despite the demonstration of altered p16 protein function in conjunction with certain polymorphisms, no such association could be established for the other polymorphisms. Although the association between the altered protein function of p16 and progression of certain malignancies, including ovarian and upper gastrointestinal cancer (18)(19)(20), has been demonstrated, a similar correlation has not been established for pituitary adenomas and their progression.…”

“…Genomic DNA was extracted from whole blood using a DZ DNA isolation kit (Dr Zeydanlı Life Science Ltd., Ankara, Turkey) according to the manufacturer's instructions. Genotypic analysis of the p16(CDKN2A) C540G polymorphism was performed using a modified polymerase chain reaction (PCR)-restriction fragment length polymorphism assay, reported previously (20). The primers for amplifying the p16(CDKN2A) C540G polymorphism were forward, 5'-GATGT GCCACACATCTTTGACCT-3'; and reverse, 5'-CTACGAAAG CGGGGTGGGTTGT-3' .…”

Polymorphisms in TP53 (rs1042522), p16 (rs11515 and rs3088440) and NQO1 (rs1800566) Genes in Thai Cervical Cancer Patients with HPV 16 Infection

“…CDK4 and CDK6 bind with the p16 gene product to inhibit interaction with cyclin D1 which prevents retinoblastoma protein (pRb) phosphorylation and release of E2F thus leading to cell cycle inhibition in the G1/S transition (Yan et al, 2008). The over-expression of p16 due to inactivation of Rb by the HPV E7 protein may act as a specific biomarker for cervical cancers.…”