Association between ESR1, ESR2, HER2, UGT1A4, and UGT2B7 polymorphisms and breast Cancer in Jordan: a case-control study

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

doi:10.1186/s12885-019-6490-7

Laith N Al-Eitan, Rame H Khasawneh + Show 2 more

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https://doi.org/10.1186/s12885-019-6490-7

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Abstract

BackgroundBreast cancer risk, development, and treatment are influenced by genetic variation in certain genes, namely those involved in cell proliferation, tumor suppression, and drug metabolism. In turn, the relevance of the aforementioned genetic variation to cancer depends on the ethnic group in question, highlighting the need for population-specific association studies. Therefore, the objective of the present study was to investigate the association between certain ESR1, ESR2, HER2, UGT1A4, and UGT2B7 single nucleotide polymorphisms and breast cancer.MethodsBlood samples were collected from 437 Jordanian-Arab breast cancer patients and healthy volunteers and subject to genotyping using the Sequenom MassARRAY® system (iPLEX GOLD).ResultsOur findings show a significant association between breast cancer and the allelic (P = 0.02486879) and genotypic (P = 0.04793066) frequencies of the ESR1 polymorphism rs3798577, a result which was confirmed in different genetic models. No other investigated polymorphism showed a significant association with breast cancer itself in Jordanian Arabs, but the Rare Hz (GG) vs Het (AG) genetic model revealed an association of the disease with the ESR1 polymorphism rs3798577. However, several associations were found between certain polymorphisms and breast cancer’s prognostic factors.ConclusionThis study suggests that certain polymorphisms may increase the risk of breast cancer in the Jordanian-Arab population. Future research and clinical translation could incorporate the current results in preventative breast cancer approaches tailored for Jordanian-Arab patients.

Highlights

Breast cancer risk, development, and treatment are influenced by genetic variation in certain genes, namely those involved in cell proliferation, tumor suppression, and drug metabolism
Association between Breast cancer (BC) and estrogen receptor 1 (ESR1), estrogen receptor 2 (ESR2), Human epidermal growth factor receptor 2 marker (HER2), UDP glucuronosyltransferase 1A4 (UGT1A4), and UDP glucuronosyltransferase 2B7 (UGT2B7) single nucleotide polymorphisms (SNPs) Table 2 summarizes the findings of the present study with regard to genetic association with BC
Our findings show that the ESR1 polymorphism rs3798577 was significantly associated with BC and history of BC in the Jordanian-Arab population, and it was found to confer higher BC risk in the TunisianArab population [38]. rs3978577 polymorphism is located in the 3′ UTR of ER-α, and it has been suggested to increased the overall risk of BC [25]

Summary

Introduction

Development, and treatment are influenced by genetic variation in certain genes, namely those involved in cell proliferation, tumor suppression, and drug metabolism. Breast cancer (BC) is a complex disease that arises due to a combination of environmental and genetic factors [1]. Mutations in the BRCA1 and BRCA2 genes have been wellestablished as risk factors for BC development, and they are responsible for approximately 90% of the disease’s. The estrogen receptor 1 (ESR1) and estrogen receptor 2 (ESR2) genes encode for AL-Eitan et al BMC Cancer (2019) 19:1257 estrogen receptors alpha (ER-α) and beta (ER-β), respectively, which are activated by estrogen and interact with one another in a dimeric manner [10]. Genetic variants in genes that encode estrogen receptors such as ESR on chromosome 6, could expose a potential risk for breast cancer. Several studies reported that about 55% of ERpositive metastatic BC patients were screened with ESR1 mutations [12,13,14,15]

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