Association of a miR-502-binding site single nucleotide polymorphism in the 3'-untranslated region of SET8 and the TP53 codon 72 polymorphism with cervical cancer in the Chinese population.

Shao-Di Yang,Wen Li,Jian-Xin Tang,Pei Jiang,Yan-Lin Cai

doi:10.7314/apjcp.2014.15.16.6505

Abstract

This study was conducted to identify whether polymorphic variants of set domain-containing protein 8 (SET8) and tumor protein p53 (TP53) codon 72, either independently or jointly, might be associated with increased risk for cervical cancer. We genotyped SET8 and TP53 codon 72 polymorphisms of peripheral blood DNA from 114 cervical cancer patients and 200 controls using the polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) and direct DNA sequencing. The frequency of SET8 CC (odds ratios (OR) = 2.717, 95% CI=1.436-5.141) or TP53 GG (OR=2.168, 95% CI=1.149-4.089) genotype was associated with an increased risk of cervical cancer on comparison with the SET8 TT or TP53 CC genotypes, respectively. In additional, interaction between the SET8 and TP53 polymorphisms increased the risk of cervical cancer in a synergistic manner, with the OR being 9.913 (95% CI=2.028-48.459) for subjects carrying both SET8 CC and TP53 GG genotypes. These data suggest that there are significant associations between the miR-502-binding site SNP in the 3'-UTR of SET8 and the TP53 codon 72 polymorphism with cervical cancer in Chinese, and there is a gene-gene interaction.

Highlights

Cervical cancer is the second common gynecologic malignant tumor in the world, and it remains a leading cause of cancer-related death for women in developing countries (Akinyemiju, 2012; Ginsberg et al, 2012; Shuai et al, 2012; Gocze et al, 2013)
The odds ratios (ORs) significantly increased to 9.913 among subjects carrying both set domain-containing protein 8 (SET8) CC and tumor protein p53 (TP53) GG genotypes. These results clearly indicated a significant interaction between the SET8 CC and TP53 GG genotype on the increased risk of developing cervical cancer according to the statistical model
1 1.652 (0.976-2.797) 2.065 (1.041-4.097)* 9.913 (2.028-48.459)*. This is the first study demonstrating the effects of the association between the miR-502-binding site SNP in the 3’-UTR of SET8 and the TP53 codon 72 polymorphisms and the risk of cervical cancer

Summary

Introduction

Cervical cancer is the second common gynecologic malignant tumor in the world, and it remains a leading cause of cancer-related death for women in developing countries (Akinyemiju, 2012; Ginsberg et al, 2012; Shuai et al, 2012; Gocze et al, 2013). The HPV infection is known to be a high-risk factor in cervical carcinogenesis, only a small proportion of such HPV-infected cases progress to cervical cancer. It indicates that genetic factors may be an important factor in the development of cervical cancer (Moore et al, 2012). Set domain-containing protein 8 (SET8, known as PR-SET7) is located on chromosme 12q24.31. It is a histone H4-Lys-20-specific methyltransferase that plays a significant role in cell-cycle-dependent transcriptional silencing and mitotic regulation in metazoans (Beck et al, 2012). Mutation in either SET8 or TP53 may lead to loss of homeostatic control during human carcinogenesis

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Conclusion