Abstract

Breast cancer (BC) pathogenesis is poorly understood and not yet completely determined. BC susceptibility genes are responsible for 20% to 25% of breast cancer risk. The main objective of this study is to identify the genetic polymorphisms within the Harvey rat sarcoma viral oncogene homolog (HRAS1) and interleukin-1 receptor antagonist (IL1-Ra) genes in Jordanian BC female patients and to investigate the genetic association of these polymorphisms with BC. Samples were collected from 150 Jordanian BC patients and 187 healthy age-matched controls. PCR and PCR-RFLP techniques were used to identify genetic polymorphisms within these candidate genes. The single nucleotide polymorphism single nucleotide polymorphism (SNP) association web tool SNPStats (v. 3.6) was used to investigate the allelic and genotypic association with BC. Different statistical analyses were used to study the correlation between the investigated genetic variants and several prognosis factors of BC. A genetic association between BC susceptibility and Il-1β rs1143634 was found specifically at the allelic level of E1 as a risk allele (72% in the cases vs. 64.2% in the controls). Another genetic association was found in the IL-Ra gene (86-VNTR (variable number tandem repeat)), which presented one repeat allele (24.1% in cases vs. 15.59% in controls) and could be considered as a risk allele in Jordanian women. In contrast, this study found that there is no genetic association between Il-1β SNP rs16944 and BC. In addition, a significant association was found between the allelic level of the HRAS1 gene and BC susceptibility. Since this study is the first to be conducted on the genetic susceptibility of these genes to BC in the Jordanian population, more investigations on the link between BC and these variants are recommended to determine the impact of these polymorphisms on other ethnic groups.

Highlights

  • Breast cancer (BC) is an accumulation of different malignancies that present in the mammary glands

  • In agreement with previous data and studies, our results showed that there was no association between HRAS1 and BC at the genotypic level, but, in contrast, HRAS1 was significantly associated with BC susceptibility at the allelic level

  • To the best of our Knowledge, this study is the first of its kind to investigate the genetic association of IL-1 and HRAS1 (28bp-Variable number tandem repeat (VNTR)) gene polymorphisms with the risk of BC in a Jordanian population of Arab descent

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Summary

Introduction

Breast cancer (BC) is an accumulation of different malignancies that present in the mammary glands. BC has the highest incidence of all cancers in women worldwide [1]. Among the Jordanian population, BC was ranked number one of the three most common cancers among Jordanian females, as reported by the Jordan Cancer Registry [2]. It was reported to be the second cause of death after cardiovascular diseases among women [3]. According to the Ministry of Health, BC accounted. Cancers 2020, 12, 283 for nearly 40% of all cancers that affect Jordanian women, with the median age at first diagnosis being 51 [3]. BC etiology is complex as many genes are involved in multiple stages of cancer development [4]

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