ESR2 gene variants (rs1256049, rs4986938, and rs1256030) and their association with breast cancer risk

Martha Patricia Gallegos-Arreola; Guillermo M Zúñiga-González; Luis E Figuera; Ana María Puebla-Pérez; María Guadalupe Márquez-Rosales; Belinda Claudia Gómez-Meda; Mónica Alejandra Rosales-Reynoso

doi:10.7717/peerj.13379

ESR2 gene variants (rs1256049, rs4986938, and rs1256030) and their association with breast cancer risk

PeerJ. 2022 May 10:10:e13379. doi: 10.7717/peerj.13379. eCollection 2022.

Authors

Martha Patricia Gallegos-Arreola¹, Guillermo M Zúñiga-González², Luis E Figuera¹, Ana María Puebla-Pérez³, María Guadalupe Márquez-Rosales¹, Belinda Claudia Gómez-Meda⁴, Mónica Alejandra Rosales-Reynoso²

Affiliations

¹ División de Genética, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, México.
² División de Medicina Molecular, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, México.
³ Laboratorio de Inmunofarmacología, Departamento de Farmacología, Centro Universitario de Ciencias Exactas e Ingenierías, Universidad de Guadalajara, Guadalajara, Jalisco, México.
⁴ Departamento de Biología Molecular y Genómica, Instituto de Genética Humana "Dr. Enrique Corona Rivera", Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México.

Abstract

Background: Variants of the estrogen receptor b (ESR2) gene have been associated with different types of cancer. However, these associations have been inconsistent. We genotyped the ESR2 variants (rs1256049, rs4986938, and rs1256030) in breast cancer (BC) patients and in healthy women.

Results: The variants rs1256049 and rs4986938 in the ESR2 gene were not associated with risk susceptibility in BC patients. However, the rs1256030 variant had an association as a risk factor for BC patients when compared with controls and BC patients for the TT genotype (odds ratio (OR) 1.86, 95% confidence intervals (CI) [1.05-3.28], p = 0.042). In addition, differences were observed in patients and controls carrying the TT genotype under 50 years of age (OR 1.85, 95% CI [1.05-3.27], p = 0.043). Thus, evident differences showed the rs1256030 variant in patients with TT, TC, and TC+TT genotypes with: (1) Stage IV (OR 1.60, 95% CI [1.06-2.54], p = 0.033), and (2) Luminal A (OR 1.60, 95% CI [0.47-0.21], p = 0.041), as well as in BC carriers of the TT genotype with indices of cellular proliferative (Ki-67) elevated (>20%) and overweight (OR 1.67, 95% CI [0.85-3.28], p = 0.041), respectively. In BC HER2 with lymph node metastasis, the TT genotype was a protective factor (OR 0.38, 95% CI [0.18-0.78], p = 0.005). The identification of haplotypes included two common GAT as risk factors (OR 3.1, 95% CI [1.31-7.72], p = 0.011) and GGC as a protective factor (OR 0.7, 95% CI [0.60-0.97], p = 0.034). The haplogenotype GGGATC was a risk factor (OR 2.5, 95% CI [1.28-5.0], p = 0.008).

Conclusion: The variant rs1256030 (TT) of the ESR2 gene and haplotype GAT were associated with susceptibility to BC as risk factors in this sample from the Mexican population.

Keywords: Breast cancer; ESR2; Polymorphisms; Variants; rs1256030; rs1256049; rs4986938.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Breast Neoplasms* / epidemiology
Case-Control Studies
Estrogen Receptor beta / genetics
Female
Humans
Polymorphism, Single Nucleotide / genetics
Risk Factors

Substances

Estrogen Receptor beta
ESR2 protein, human

Grants and funding

This research was financially supported through FIS/IMSS/PROT/G17/1661 grants. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.