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      Genetic polymorphisms of estrogen receptor genes are associated with breast cancer susceptibility in Chinese women

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          Abstract

          Background

          Estrogen exposure is a widely known risk factor for BC. And the interaction of estrogen with estrogen receptor (ER) plays an important role in breast cancer development. This case–control study aims to assess the association of genetic polymorphisms in the estrogen receptor genes with breast cancer (BC) susceptibility in Chinese Han women.

          Methods

          Four polymorphisms (rs2881766, rs9383951, rs9340799 in ESR1 and rs3020449 in ESR2) were genotyped in 459 patients and 549 healthy controls using the Sequenom MassARRAY method. Odds ratio (OR) and 95% confidence intervals (95% CI) were calculated to evaluate the associations. False-positive report probability (FPRP) was utilized to examine the noteworthiness of significant findings.

          Results

          We observed that rs2881766 was associated with a decreased BC risk (GG vs. TT: OR = 0.63, 95% CI = 0.44–0.91; GG vs. TT/GT: OR = 0.68, 95% CI = 0.49–0.95), while rs3020449 was associated with an increased risk of BC (CT vs. TT: OR = 1.58, 95% CI = 1.21–2.06; CT/CC vs. TT: OR = 1.54, 95% CI = 1.20–1.98; TT/CC vs. CT: OR = 1.48, 95% CI = 1.15–1.90). The other two polymorphisms have no relation with BC susceptibility. In addition, rs2881766 was correlated with lymph node metastasis and ER expression, and rs3020449 was related to tumor size, histological grade and ER expression. The values of false-positive report probability indicated that the significant associations of BC risk with both rs2881766 and rs3020449 were noteworthy.

          Conclusions

          Our study suggests that polymorphisms rs2881766 and rs3020449 in estrogen receptor genes were associated with BC susceptibility as well as clinical features in Chinese women. These findings need further validation in a large population.

          Electronic supplementary material

          The online version of this article (10.1186/s12935-019-0727-z) contains supplementary material, which is available to authorized users.

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          Most cited references21

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          Genetic susceptibility to breast cancer.

          Anne-Lise Børresen-Dale, Therese Sørlie, Vessela Kristensen … (2010)
          Genetic and lifestyle/environmental factors are implicated in the aetiology of breast cancer. This review summarizes the current state of knowledge on rare high penetrance mutations, as well as moderate and low-penetrance genetic variants implicated in breast cancer aetiology. We summarize recent discoveries from large collaborative efforts to combine data from candidate gene studies, and to conduct genome-wide association studies (GWAS), primarily in breast cancers in the general population. These findings are compared with results from collaborative efforts aiming to identify genetic modifiers in BRCA1 and BRCA2 carriers. Breast cancer is a heterogeneous disease, and tumours from BRCA1 and BRCA2 carriers display distinct pathological characteristics when compared with tumours unselected for family history. The relationship between genetic variants and pathological subtypes of breast cancer, and the implication of discoveries of novel genetic variants to risk prediction in BRCA1/2 mutation carriers and in populations unselected for mutation carrier status, are discussed. (c) 2010. Published by Elsevier B.V.
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            Estrogen receptor alpha gene polymorphisms and breast cancer risk.

            Aesun Shin, Daehee Kang, Hisahide Nishio … (2003)
            We conducted a hospital-based case-control study to evaluate the association between the XbaI and PvuII restriction fragment length polymorphisms (RFLPs) in intron I of the estrogen receptor alpha (ER alpha) gene and breast cancer risk. The study population consisted of 205 histologically confirmed incident breast cancer cases and 205 age-matched controls with no present and previous history of cancer. The PvuII genotype distribution did not show any difference between cases and controls, but the adjusted odds ratio (OR) for the XbaI X allele containing genotypes was 0.4 (95% CI: 0.3-0.6) compared with the xx genotype. The decrease in the OR appeared to be more attributable to the postmenopausal women; the ORs were 0.3 (95% CI: 0.1-0.5) and 0.5 (95% CI: 0.3-0.9) for postmenopausal and premenopausal women, respectively. Our results therefore suggest that the ER alpha XbaI polymorphism modifies individual susceptibility to breast cancer in Korean women.
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              Genetic polymorphisms (rs10636 and rs28366003) in metallothionein 2A increase breast cancer risk in Chinese Han population

              Di Liu, Meng Wang, Tian Tian … (2017)
              Genetic polymorphisms of MT2A are frequently observed in many different cancers. We performed this case-control study, including 459 breast cancer (BC) patients and 549 healthy controls from Northwest China, to evaluate the associations between two common MT2A polymorphisms (rs10636 and rs28366003) and BC risk. The MT2A polymorphisms were genotyped via Sequenom MassARRAY. The individuals with the rs28366003 A/G, A/G-G/G genotypes underwent a higher risk of BC (P<0.0001). And, the minor allele G of rs28366003 was related to an increased BC risk (P<0.0001). We also found a significantly increased BC risk with rs10636 polymorphism among homozygote and recessive models (P<0.05). Further subgroup analysis by clinical characteristics of BC patients showed that Scarff, Bloom and Richardson tumor grade (SBR) 1-2 have a higher expression of the minor allele of these two MT2A loci than SBR 3. Our results indicated that the rs10636 and rs28366003 polymorphisms in MT2A increased BC risk in Northwest Chinese Han population.  
              Article 0 comments Cited 20 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Zhijun Dai:
                ORCID: http://orcid.org/0000-0001-5209-8626
                dzj0911@126.com
                Tian Tian: tt20060104@163.com
                Meng Wang: wmeng0308@126.com
                Tielin Yang: yangtielin@mail.xjtu.edu.cn
                Hongtao Li: lht4656@163.com
                Shuai Lin: voyage420@163.com
                Qian Hao: 369182730@qq.com
                Peng Xu: 164911802@qq.com
                Yujiao Deng: 939477445@qq.com
                Linghui Zhou: 2544928065@qq.com
                Na Li: 865117802@qq.com
                Yan Diao: dy971203@163.com
                Journal
                Journal ID (nlm-ta): Cancer Cell Int
                Journal ID (iso-abbrev): Cancer Cell Int
                Title: Cancer Cell International
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1475-2867
                Publication date (Electronic): 8 January 2019
                Publication date PMC-release: 8 January 2019
                Publication date Collection: 2019
                Volume: 19
                Electronic Location Identifier: 11
                Affiliations
                [1 ]ISNI 0000 0000 8653 1072, GRID grid.410737.6, Department of Breast Surgery, Guangzhou Women and Children’s Medical Center, , Guangzhou Medical University, ; Guangzhou, 510623 Guangdong China
                [2 ]GRID grid.452672.0, Department of Oncology, , The Second Affiliated Hospital of Xi’an Jiaotong University, ; Xi’an, 710004 China
                [3 ]ISNI 0000 0001 0599 1243, GRID grid.43169.39, School of Life Science and Technology, , Xi’an Jiaotong University, ; Xi’an, 710049 China
                [4 ]ISNI 0000 0004 1799 3993, GRID grid.13394.3c, Department of Breast Head and Neck Surgery, , The 3rd Affiliated Teaching Hospital of Xinjiang Medical University (Affiliated Tumor Hospital), ; Urumqi, 830000 China
                Author information
                http://orcid.org/0000-0001-5209-8626
                Article
                Publisher ID: 727
                DOI: 10.1186/s12935-019-0727-z
                PMC ID: 6325673
                SO-VID: f3dc8cbc-05aa-415e-8170-a37a185fbae9
                Copyright © © The Author(s) 2019
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 9 July 2018
                Date accepted : 2 January 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81471670
                Award Recipient :
                Funded by: Key research and development plan, Shaanxi Province, People’s Republic of China
                Award ID: 2017ZDXM-SF-066
                Award Recipient :
                Funded by: Science and technology branch project of Xinjiang Uygur Autonomous Region, People’s Republic of China
                Award ID: 2017E0262
                Award Recipient :
                Categories
                Subject: Primary Research
                Custom metadata
                issue-copyright-statement © The Author(s) 2019

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: estrogen receptor genes,polymorphism,breast cancer,susceptibility
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: estrogen receptor genes, polymorphism, breast cancer, susceptibility

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