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Potential impact of (rs 4645878) BAX promoter −248G>A and (rs 1042522) TP53 72Arg>pro polymorphisms on epithelial ovarian cancer patients

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Abstract

Background

In India, Epithelial ovarian cancer has emerged as one of the most common malignancies affecting women. Tumor protein 53 (TP53) induces expression of the B cell lymphoma 2-associated X protein (BAX) gene by directly binding to the TP53-binding element in the BAX promoter. Therefore, we hypothesized that single-nucleotide polymorphism of BAX promoter −248G>A and TP53 72Arg>Pro gene may jointly contribute to ovarian cancer risk.

Objectives

This study aimed at exploring the association of BAX promoter −248G>A and TP53 72Arg>Pro gene polymorphism with risk of developing EOC and its clinicopathological features and to evaluate gene–gene interaction of these two polymorphisms with risk of developing EOC.

Materials

The study was conducted on 70 Epithelial ovarian cancer patients and 70 healthy controls. Genotyping of p53 codon 72 and BAX promoter gene was examined by ASO-PCR and PICA-PCR, respectively. Odds ratios and 95 % confidence intervals were calculated.

Results

We found an increased cancer risk associated with the BAX AA (ORs = 4.1, 95 %, CI = 1.23–13.97) genotype. An increased risk was also associated with the TP53 Pro/Pro (OR = 4.4, 95 % CI = 1.40–13.99) and Arg/Pro genotype (OR = 2.3, 95 % CI = 1.13–4.86). The gene–gene interaction of these polymorphisms increased EOC risk in a more than additive manner (ORs for the presence of both BAX AA and TP53 Arg/Pro genotypes = 8.7, 95 % CI = 1.66–45.48). BAX GG genotype was associated with adverse staging of cancer (P = 0.01).

Conclusions

The findings suggest that polymorphism of BAX and TP53 genes may be potential genetic modifiers for developing ovarian cancer.

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Abbreviations

ASO PCR:

Allele specific PCR

EOC:

Epithelial ovarian cancer

PCR:

Polymerase chain reaction

PIRA PCR:

Primer introduced restriction analysis

SNP:

Single-nucleotide polymorphism

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Conflict of interest

The authors declare that they have competing interests for closely related research articles.

Authors’ contributions

DS was involved in conception and design of study, processing of samples, molecular genetics work and interpretation of data. RM has made substantial contributions to conception and design of study, interpretation of data and molecular genetics work. MZ was involved in interpretation of data and molecular genetics work. PY was involved in interpretation of data and molecular genetics work. GG was involved in collection of samples and clinical staging of cases. NK was involved in assisting in the histopathological studies in this work. AS was involved in carrying out molecular genetics studies. All authors read and approved the final manuscript. PCR was involved in carrying out design of study, molecular genetics studies and correction of manuscript.

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Correspondence to R. Mir.

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Dholariya, S., Mir, R., Zuberi, M. et al. Potential impact of (rs 4645878) BAX promoter −248G>A and (rs 1042522) TP53 72Arg>pro polymorphisms on epithelial ovarian cancer patients. Clin Transl Oncol 18, 73–81 (2016). https://doi.org/10.1007/s12094-015-1338-3

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  • DOI: https://doi.org/10.1007/s12094-015-1338-3

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