Association of rs1042522 SNP with Clinicopathologic Factors of Breast Cancer Patients in the Markazi Province of Iran

Abstract

Background: The nucleotide changes in different genetic loci increased the incidence risk of breast cancer.

Aim: The aim of present study was to investigate genotype distribution at codon 72 of the TP53 gene (rs1042522) in breast cancer patients to achieve a potential diagnostic marker related to some demographic feathers.

Methods: In our case-control study, blood samples were collected from a total of 34 patients harboured breast cancer. DNA was extracted, and nested-PCR was performed. Products were digested with AccII and subsequently were sequenced. Results were compared with samples characteristics.

Results: The PCR results indicated the correct implementation of extraction and amplification protocol. The genotypic distribution at codon 72 of TP53 in control group was 20%, 62.4% and 16.6% for Arg (wildtype), Arg/Pro (heterozygous) and Pro (homozygous variant) respectively. Also, this distribution in the patient group was 23.52% homozygous, 50% heterozygous, and 26.47% another homozygous variant (Adjusted odds ratio: 1.12 and 95%CI = 0.57 to 2.2, P = 0.03). The absence of Arg at codon 72 of TP53 is relevant with age higher than 40 years and metastasis to other organs.

Conclusion: Polymorphism at codon 72 of TP53 was associated with high-grades of breast cancer risk and different responses to chemotherapy treatment. It is recommended genotype distribution of codon 72 of TP53 before chemotherapy.

Keywords: Breast cancer; Chemotherapy; Nested-PCR; TP53.

Figure 1

View of the TP53 chromosome position and the Ensemble databank of variants and SNPs of the TP53 gene. The codon 72 is shown by the blue arrow

Figure 2

Steps of Nested-PCR steps in this study. The yellow arrow shows the 300 bp amplicon of TP53 gene

Figure 3

A) Agarose gel of digestion reaction. Column 1-4 showed heterozygote samples (Arg/Pro) and column 5 showed a homozygote wildtype (Arg); B) Nucleotide sequences from the sequencing of clinical samples (Chromas and Mega4 software)

Figure 4

A) This chart shows the relationship between amplicons sequences and the characteristics of the used clinical samples; B) GraphPad Prism 7.0 software showed association between the Pro at codon 72 of TP53 gene and the Age > 40, BMI > 22, WHR > 0.8 and negative response to chemotherapy (One-way ANOVA test, P = 0.03)