The Association of IL-1 and HRAS Gene Polymorphisms with Breast Cancer Susceptibility in a Jordanian Population of Arab Descent: A Genotype-Phenotype Study

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.

Keywords: HRAS; IL-1; breast cancer; cancer susceptibility; genetic association; single nucleotide polymorphism.

Figure 1

Agarose gel electrophoresis showing different polymorphisms in the IL-1 and HRAS genes: (A) PCR-RFLP genotypes in the IL-1 promoter gene according to the single nucleotide polymorphism (SNP) rs16944. (B) PCR-RFLP genotypes in the IL-1 exon5 gene according to the SNP rs1143634. (C) Variable number tandem repeat (VNTR) genotypes in the IL-1Ra variable number polymorphism with 86 bp repeats. (D) VNTR genotypes in the HRAS1 gene variable number polymorphism with 28 bp repeats.