Association analysis of p16 (CDKN2A) and RB1 polymorphisms with susceptibility to cervical cancer in Indian population

Abstract

The potent tumor suppressors P16 and RB1 are the key regulators of cell cycle machinery in eukaryotes. Polymorphisms in these genes play an important role in the outcome of various diseases including cancer. In the present study, we evaluated the association of p16 and RB1 polymorphisms with cervical cancer susceptibility in Indian population. We screened 150 histologically confirmed cervical cancer cases along with equal number of healthy controls with normal cervical cytology. PCR-RFLP method was employed for genotyping of SNPs in p16 C540G (rs11515), C580T (rs3088440) in the 3'-UTR of exon 3 and RB1 A153104G (rs4151580) located in the intron 18 and confirmed by direct sequencing. Both patients and controls were screened for HPV infection. In this case-control study 84.67% (127/150) of cases were found to be positive for HPV DNA sequence. Women carrying p16 C540G carrier genotypes 540 (CG/GG) may have protective effect for the development of cervical cancer (P=0.0001, OR=0.31, 95% CI=0.17-0.56). And SNP at C580T of p16 gene was found to be negatively associated with the risk of cervical cancer (P=0.0004, OR=0.04, 95% CI=0.002-0.63). p16 (540C/580T) has emerged as a major risk haplotype (P=0.033, OR=1.47, 95% CI=1.05-2.07) whereas p16 (540G/580T) as a chief protective haplotype (P=0.014, OR=0.39, 95% CI=0.18-0.83) for the development of cervical cancer among Indian women. Contrary to this, SNP at A153104G of RB1 gene showed statistically significant association (P=0.035, OR=1.69, 95% CI=1.06-2.68) with increased susceptibility for the development of cervical cancer. Our results suggest that single nucleotide polymorphisms in p16, RB1 genes may affect the susceptibility to cervical cancer collectively.

Combination of genetic variants in cyclin D1 and retinoblastoma genes predict clinical outcome in oral cancer patients

“…However, further studies elucidating the downstream effects of this polymorphism are warranted. The effect of RB1 polymorphisms on the susceptibility of various other cancers such as breast cancer [35], ovarian cancer [36,37], uterine cervical cancer [38], and colorectal cancer [39] have also been reported, thus substantiating the crucial role of this protein in cancer. Previous study from our lab on oral cancer risk found the significant influence of another RB1 polymorphism, rs3092904, on oral cancer susceptibility [23].…”

Polymorphisms of cell cycle control genes influence the development of sporadic medullary thyroid carcinoma

“…The SNP (rs11515 -C98A) CDKN2A gene determines a non-synonymous serine-to-arginine substitution located in the 3 0 -UTR of exon 3 (36). In fact, similarly, we observed for s-MTC, CDKN2A gene rs11515 polymorphism was also considered a protective factor against cervical cancer (35). CDKN2A gene (rs11515) polymorphism may affect the DNAbinding zinc finger motif, thus modifying p21 expression and function (37).…”

“…CDKN2A gene polymorphisms have largely been investigated in different types of cancers (20,22,35). The SNP (rs11515 -C98A) CDKN2A gene determines a non-synonymous serine-to-arginine substitution located in the 3 0 -UTR of exon 3 (36).…”

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

“…By contrast, a study by Geddert et al (30) indicated that these polymorphisms had no association with upper gastrointestinal and oesophageal adenocarcinomas. Previous studies have shown that these polymorphisms are associated with the progression of ovarian and upper gastrointestinal cancers, despite uncertainty regarding the progression of cervical cancer (31,32). A study by Chen et al (33) reported that in patients with the polymorphic genotype for C540G there was no significant increase in the hazard ratio (HR) for the age-related pancreatic cancer risk, as compared with those with wild-type genotype [HR, 0.80; 95% confidence interval (CI): 0.56-1.17] and there was a only a marginally significant increase in the HR for C580T (HR, 1.52; 95% CI: 1.00-2.30).…”