Association of p21 SNPs and risk of cervical cancer among Chinese women

BMC Cancer, Dec 2012

Background The p21 codon 31 single nucleotide polymorphism (SNP), rs1801270, has been linked to cervical cancer but with controversial results. The aims of this study were to investigate the role of p21 SNP-rs1801270 and other untested p21 SNPs in the risk of cervical cancer in a Chinese population. Methods We genotyped five p21 SNPs (rs762623, rs2395655, rs1801270, rs3176352, and rs1059234) using peripheral blood DNA from 393 cervical cancer patients and 434 controls. Results The frequency of the rs1801270 A allele in patients (0.421) was significantly lower than that in controls (0.494, p = 0.003). The frequency of the rs3176352 C allele in cases (0.319) was significantly lower than that in controls (0.417, p < 0.001).The allele frequency of other three p21 SNPs showed not statistically significantly different between patients and controls. The rs1801270 AA genotype was associated with a decreased risk for the development of cervical cancer (OR = 0.583, 95%CI: 0.399 - 0.853, P = 0.005). We observed that the three p21 SNPs (rs1801270, rs3176352, and rs1059234) was in linkage disequilibrium (LD) and thus haplotype analysis was performed. The AGT haplotype (which includes the rs1801270A allele) was the most frequent haplotype among all subjects, and both homozygosity and heterozygosity for the AGT haplotype provided a protective effect from development of cervical cancer. Conclusions We show an association between the p21 SNP rs1801270A allele and a decreased risk for cervical cancer in a population of Chinese women. The AGT haplotype formed by three p21 SNPs in LD (rs1801270, rs3176352 and rs1059234) also provided a protective effect in development of cervical cancer in this population.

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Association of p21 SNPs and risk of cervical cancer among Chinese women

BMC Cancer Association of p21 SNPs and risk of cervical cancer among Chinese women Ning Wang 0 Shizhuo Wang 0 Qiao Zhang 0 Yanming Lu 0 Heng Wei 0 Wei Li 0 Shulan Zhang 0 Duo Yin 0 Yangling Ou 0 0 Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University , Shenyang , China Background: The p21 codon 31 single nucleotide polymorphism (SNP), rs1801270, has been linked to cervical cancer but with controversial results. The aims of this study were to investigate the role of p21 SNP-rs1801270 and other untested p21 SNPs in the risk of cervical cancer in a Chinese population. Methods: We genotyped five p21 SNPs (rs762623, rs2395655, rs1801270, rs3176352, and rs1059234) using peripheral blood DNA from 393 cervical cancer patients and 434 controls. Results: The frequency of the rs1801270 A allele in patients (0.421) was significantly lower than that in controls (0.494, p = 0.003). The frequency of the rs3176352 C allele in cases (0.319) was significantly lower than that in controls (0.417, p < 0.001).The allele frequency of other three p21 SNPs showed not statistically significantly different between patients and controls. The rs1801270 AA genotype was associated with a decreased risk for the development of cervical cancer (OR = 0.583, 95%CI: 0.399 - 0.853, P = 0.005). We observed that the three p21 SNPs (rs1801270, rs3176352, and rs1059234) was in linkage disequilibrium (LD) and thus haplotype analysis was performed. The AGT haplotype (which includes the rs1801270A allele) was the most frequent haplotype among all subjects, and both homozygosity and heterozygosity for the AGT haplotype provided a protective effect from development of cervical cancer. Conclusions: We show an association between the p21 SNP rs1801270A allele and a decreased risk for cervical cancer in a population of Chinese women. The AGT haplotype formed by three p21 SNPs in LD (rs1801270, rs3176352 and rs1059234) also provided a protective effect in development of cervical cancer in this population. P21; Single nucleotide polymorphism; Cervical cancer; Haplotype - Background Cervical cancer is the second most common cancer in women worldwide [1,2]. The human papilloma virus (HPV) appears to be a necessary factor in the development of almost all cases (> 90%) of cervical cancer [3]. The HPV E6 and E7 proteins are viral genes expressed in virtually all HPV-positive cervical carcinomas, and many experiments have shown that these are cooperative viral oncoproteins [4] that inactivate p53 and retinoblastoma (pRb) tumor suppressors, promoting carcinogenesis [4,5]. HPV infection is relatively common while only a small fraction of those infected develop cancer, suggesting that additional environmental, genetic, or immunological factors contribute to the progression to cervical cancer [6,7]. Cell cycle progression is regulated by cyclindependent kinases, crucial for normal growth and differentiation. Disruption of cell cycle control is common in cancer cells and is believed to play an essential role in cancer initiation and development. The cyclindependent kinase inhibitor p21 (also known as WAF1or CIP1) is encoded by the CDKN1A gene located on chromosome 6p21.2 [8,9]. The p21 protein binds to and inhibits the activity of cyclin-CDK2 or -CDK4 complexes, and disrupts cell cycle progression at G1 phase [10,11]. The expression of p21 is induced by the binding of tumor suppressor protein p53 to the p21 promoter [12-14]. The p21 protein can also interact with proliferating cell nuclear antigen (PCNA), a DNA polymerase accessory factor, and plays a regulatory role in S phase DNA replication and DNA damage repair [15]. Therefore, alteration in the p21 functional and/or promoter regions may adversely affect the regulation of cellular proliferation and increase susceptibility to cancer. Identification of several genetic variants in p21 have been associated with cervical cancer [16,17]. The p21 single nucleotide polymorphism (SNP) rs1801270C/A, which occurs in codon 31, results in an amino acid substitution of arginine for serine. This polymorphism is located in a highly conserved region of p21 and is expected to affect its molecular function [18]. Prior studies have linked the p21 codon 31 SNP (rs1801270) to cervical cancer, with conflicting results [19,20]. In this study, we genotyped five p21 SNPs (rs1801270 at codon 31, rs762623 and rs2395655 in the promoter region, rs3176352 in an intron, and rs1059234 in the 3 noncoding region) in 393 cervical cancer patients and 434 cancer-free controls to look for any associations between SNP alleles or genotypes and cervical cancer in a Chinese population. Methods Before beginning this study, the study protocol was approved by the Ethics Committee of our hospital (Shengjing Hospital of China Medical University, Shenyang, China). Subjects We ascertained 393 patients with cervical cancer between October, 2008 and September, 2011 at the Shengjing Hospital of China Medical University. Di (...truncated)


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Ning Wang, Shizhuo Wang, Qiao Zhang, Yanming Lu, Heng Wei, Wei Li, Shulan Zhang, Duo Yin, Yangling Ou. Association of p21 SNPs and risk of cervical cancer among Chinese women, BMC Cancer, 2012, pp. 589, 12, DOI: 10.1186/1471-2407-12-589