亚甲基四氢叶酸还原酶（MTHFR）C677T和A1298C基因多态性会改变巴西女性散发性乳腺癌的风险和严重程度吗？

Can MTHFR C677T and A1298C Polymorphisms Alter the Risk and Severity of Sporadic Breast Cancer in Brazilian Women?

作者信息

Rezende Luciana Montes, Marson Fernando Augusto Lima, Lima Carmen Sílvia Passos, Bertuzzo Carmen Sílvia

机构信息

Department of Medical Genetics, Faculty of Medical Sciences, State University of Campinas - Unicamp, Cidade Universitária Zeferino Vaz, Campinas/SP, Brasil.

Department of Medical Genetics, Faculty of Medical Sciences, State University of Campinas - Unicamp, Cidade Universitária Zeferino Vaz, Campinas/SP, Brasil; Department of Pediatrics, Faculty of Medical Sciences, State University of Campinas - Unicamp, Cidade Universitária Zeferino Vaz, Campinas/SP, Brasil.

出版信息

Clin Breast Cancer. 2017 Jul;17(4):e199-e208. doi: 10.1016/j.clbc.2017.02.004. Epub 2017 Feb 16.

DOI:10.1016/j.clbc.2017.02.004

PMID:28330681

Abstract

INTRODUCTION

Polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR) modify the risk and severity of sporadic breast cancer (BC). In this context, the MTHFR C677T and A1298C polymorphisms have been associated with risk and severity of sporadic BC.

PATIENTS AND METHODS

In total, 253 women with BC and 257 controls were enrolled in this study. Polymorphisms were analyzed using restriction fragment length polymorphism - polymerase chain reaction. Epidemiology, tumor characteristics, and reproductive factors were considered in the analysis. Statistical tests included the χ test, the Fisher exact test, and the Mann-Whitney and Kruskal-Wallis tests, or parametric equivalents.

RESULTS

MTHFR polymorphisms were not a risk factor for BC. The 677CC genotype was associated with distant metastasis (odds ratio [OR] = 5.311; 95% confidence interval [CI] = 1.124-25.09) and lower estrogen receptor expression, whereas the 1298AA genotype was associated with stage 0 (OR = 0.244; 95% CI = 0.077-0.771) and increased estrogen receptor expression. In haplotype analysis, 677CC/1298AA was associated with hypertension (OR = 1.979; 95% CI = 1.036-3.782), and 677CT/1298AC was associated with invasive carcinoma of no special type (OR = 0.472; 95% CI = 0.243-0.918) and stage 0 (OR = 3.476; 95% CI = 1.341-10.47).

CONCLUSION

The MTHFR C677T and A1298C polymorphisms do not alter the risk of BC, but are associated with the clinical severity of BC.

摘要

引言

亚甲基四氢叶酸还原酶基因（MTHFR）多态性会改变散发性乳腺癌（BC）的风险和严重程度。在此背景下，MTHFR C677T和A1298C多态性与散发性BC的风险和严重程度相关。

患者与方法

本研究共纳入253例BC患者和257例对照。采用限制性片段长度多态性-聚合酶链反应分析多态性。分析中考虑了流行病学、肿瘤特征和生殖因素。统计检验包括χ检验、Fisher精确检验、Mann-Whitney检验和Kruskal-Wallis检验，或参数等效检验。

结果

MTHFR多态性不是BC的危险因素。677CC基因型与远处转移相关（比值比[OR]=5.311；95%置信区间[CI]=1.124-25.09）且雌激素受体表达较低，而1298AA基因型与0期相关（OR=0.244；95%CI=0.077-0.771）且雌激素受体表达增加。单倍型分析中，677CC/1298AA与高血压相关（OR=1.979；95%CI=1.036-3.782），677CT/1298AC与非特殊类型浸润性癌相关（OR=0.472；95%CI=0.243-0.918）和0期相关（OR=3.476；95%CI=1.341-10.47）。