Variants of estrogen receptor alpha and beta genes modify the severity of sporadic breast cancer

Autor(es)

Rezende, Luciana Montes ; Lima Marson, Fernando Augusto ; Passos Lima, Carmen Silvia ; Bertuzzo, Carmen Silvia

• Tipo de documento: Artigo Científico
• Fonte: Gene; v. 608, p. 73-78, APR 15 2017.
• Citações Web of Science: 3

Resumo

Introduction: Reproductive factors pose a risk for sporadic breast cancer (BC) development owing to the lifetime exposure to estrogen, a hormone responsible for cell proliferation in the breast. Because variants of the estrogen receptor (ER) alpha and beta genes have been associated with BC risk in numerous populations, the objective of the study was to determine whether the risk and severity of sporadic BC was associated with the rs2228480 (ESR1) and rs4986938 (ESR2) variants in a Brazilian population. Methods: A total of 253 DNA samples from sporadic BC patients and 257 DNA samples from healthy controls were studied. The samples were genotyped by PCR-RFLP. Epidemiological, clinical, and reproductive factors were analyzed. Statistical tests conducted included the chi(2) test, Fisher's exact test, and Mann-Whitney and Kruskal-Wallis tests or their parametric equivalents. Results: There was a high frequency of the rs2228480{*}GG genotype among the ER-positive tumors (OR = 2.13; 95% CI = 1.189-3.816) and it showed minor association with clinical stage 0 (OR = 0324; 95% CI = 0.116-0.904). The rs2228480{*}GA genotype was associated with minor ER expression, whereas rs2228480{*}GG was associated with high expression of the progesterone receptor (PR). The frequency of rs4986938{*}GA was high among women who breastfed (OR = 2.11; 95% CI = 1.203-3.702), and it showed high association with clinical stage 0 (OR = 4.383; 95% CI = 1.606-11.96) whereas it had minor association with systemic arterial hypertension (OR = 0.53; 95% CI = 0.319-0.880). The rs2228480{*}GG/rs4986938{*}GG haplotype occurred at a low frequency among women who breastfed (OR = 0.525; 95% CI = 0.298-0.924) but it was associated with a high expression of PR. Conclusion: The rs2228480 and rs4986938 variants did not alter sporadic BC risk, but they did modulate the BC severity. (C) 2017 Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 11/12939-4 - Associação entre polimorfismos de genes moduladores em crianças e adolescentes com asma alérgica e não alérgica: leve, moderada e grave
• Beneficiário: Fernando Augusto de Lima Marson
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 15/12858-5 - Identificação das mutações prevalentes e caracterização clínica e funcional de crianças e adultos com discinesia ciliar primária
• Beneficiário: Fernando Augusto de Lima Marson
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado