Role of Four ABC Transporter Genes in Pharmacogenetic Susceptibility to Breast Cancer in Jordanian Patients.

Laith N Al-Eitan,Doaa M Rababa’H,Rame H Khasawneh,Mansour A Alghamdi

doi:10.1155/2019/6425708

Abstract

Breast cancer pharmacogenetics is increasingly being explored due to chemotherapy resistance among certain classes of patients. The ATP binding cassette (ABC) transporter genes have been previously implicated in breast cancer progression and drug response. In the present study, single nucleotide polymorphisms (SNPs) from the ABCC1, ABCC2, ABCB1, and ABCG2 genes were screened in breast cancer patients and healthy volunteers from the Jordanian-Arab population. Only the ABCB1 SNPs showed a significant association with BC in Jordanian-Arab patients, and the ABCB1 SNP rs2032582 exhibited a strong genotypic association with BC. With regard to the clinical characteristics of BC, the ABCC2 SNPs rs2273697 and rs717620 were found to be significantly associated with age at breast cancer diagnosis and breastfeeding status, while the ABCB1 SNP rs1045642 was significantly associated with age at breast cancer diagnosis. In terms of pathological characteristics, the ABCC1 SNP rs35628 and the ABCB1 SNP rs2032582 were significantly associated with tumor size, the ABCC2 SNP rs2273697 was significantly associated with estrogen receptor status, and the ABCG2 SNP rs2231142 was significantly associated with axillary lymph node status. In this current study, we assume that significant genetic variants within the ABC superfamily may increase the risk of breast cancer among Jordanian women. Furthermore, these variants might be responsible for worse BC prognosis.

Highlights

Breast cancer (BC) is the most common female malignancy in the majority of countries [1]
All of the polymorphic single nucleotide polymorphisms (SNPs) were tested for minor allele frequencies (MAF) and Hardy-Weinberg equilibrium (HWE) p values in both the cases and controls (Table 1)
The allelic and genotypic frequencies of the ATP binding cassette (ABC) transporter SNPs were determined for both cases and controls (Table 2)

Summary

Introduction

Breast cancer (BC) is the most common female malignancy in the majority of countries [1]. Arab populations suffer from lower but steadily rising BC incidence rates compared to their American and European counterparts, and the clinical characteristics of the disease differ between the aforementioned populations [2]. Such population-level differences in BC predisposition have been attributed to genetics and have been widely investigated, with different mutations having different levels of association with BC [3].

Objectives

Methods

Results