Rezende Luciana Montes, Marson Fernando Augusto Lima, Lima Carmen Sílvia Passos, Bertuzzo Carmen Sílvia
Department of Medical Genetics, Faculty of Medical Sciences, State University of Campinas - Unicamp, Brazil.
Department of Medical Genetics, Faculty of Medical Sciences, State University of Campinas - Unicamp, Brazil; Department of Pediatrics, Faculty of Medical Sciences, State University of Campinas - Unicamp, Brazil.
Gene. 2017 Apr 15;608:73-78. doi: 10.1016/j.gene.2017.01.010. Epub 2017 Jan 18.
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.
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 χ test, Fisher's exact test, and Mann-Whitney and Kruskal-Wallis tests or their parametric equivalents.
There was a high frequency of the rs2228480GG 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=0.324; 95% CI=0.116-0.904). The rs2228480GA genotype was associated with minor ER expression, whereas rs2228480GG was associated with high expression of the progesterone receptor (PR). The frequency of rs4986938GA 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 rs2228480GG/rs4986938GG 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.
The rs2228480 and rs4986938 variants did not alter sporadic BC risk, but they did modulate the BC severity.
由于一生中暴露于雌激素（一种负责乳腺细胞增殖的激素），生殖因素会增加散发性乳腺癌（BC）发生的风险。鉴于雌激素受体（ER）α和β基因的变异已在众多人群中与BC风险相关联，本研究的目的是确定在巴西人群中，散发性BC的风险和严重程度是否与rs2228480（ESR1）和rs4986938（ESR2）变异相关。
共研究了253例散发性BC患者的DNA样本和257例健康对照的DNA样本。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）对样本进行基因分型。分析了流行病学、临床和生殖因素。所进行的统计检验包括χ检验、费舍尔精确检验、曼-惠特尼检验和克鲁斯卡尔-沃利斯检验或其参数等价检验。
在ER阳性肿瘤中，rs2228480GG基因型的频率较高（比值比[OR]=2.13；95%置信区间[CI]=1.189 - 3.816），并且与0期临床分期有较小关联（OR=0.324；95% CI=0.116 - 0.904）。rs2228480GA基因型与ER低表达相关，而rs2228480GG与孕激素受体（PR）高表达相关。rs4986938GA在母乳喂养的女性中频率较高（OR=2.11；95% CI=1.203 - 3.702），并且与0期临床分期高度相关（OR=4.383；95% CI=1.606 - 11.96），而与系统性动脉高血压有较小关联（OR=0.53；95% CI=0.319 - 0.880）。rs2228480GG/rs4986938GG单倍型在母乳喂养的女性中出现频率较低（OR=0.525；95% CI=0.298 - 0.924），但与PR高表达相关。
rs2228480和rs4986938变异并未改变散发性BC的风险，但它们确实调节了BC的严重程度。
