da Silva Nogueira José, de Lima Marson Fernando Augusto, Sílvia Bertuzzo Carmen
Department of Genetics, Faculty of Medical Sciences, University of Campinas, P.O. Box: 6111, Campinas, SP 13081-970, Brazil.
BMC Res Notes. 2012 Dec 6;5:676. doi: 10.1186/1756-0500-5-676.
Breast cancer (BC) is a genetic disorder characterized by growth and proliferation of breast cells in a disorderly. In Brazil, there are approximately 49.240 new cases of BC, every year. The BC etiology is still poorly understood. The BC can be sporadic (SBC) or hereditary (HBC). Recent studies have correlated gene polymorphisms with the BC, such as alterations in thymidylate synthase gene (TYMS), which are used to improve diagnosis and prevention of the disease. Polymorphisms in the TYMS gene 5'-UTR region, usually present reps double (2R) and/or triple (3R). Studies have shown that homozygous 3R/3R is overexpressed compared with 2R/2R genotype, and these polymorphic variations may contribute to individual susceptibility to the development of BC. In this context, the objective of this study was to evaluate the frequency of the TYMS 2R and 3R polymorphisms, comparing genotypic and allelic distribution with SBC and HBC patients.
In this study we included a total of 204 subjects, 70 with BC (33 with SBC, and 37 with HBC) and 134 healthy subjects (controls). The Polymerase Chain Reaction was the method used.
Results demonstrated a high frequency of the 3R allele at BC, SBC, and HBC groups. The frequency of genotype 2R/3R was significantly higher in BC group. This work showed association between the 2R/3R variants (OR = 4.14, CI95% = 1.77-9.71) in the development of SBC, and 2R/2R (OR = 0.233, CI95% = 1.63-7.65) and 2R/3R (OR = 3.53, CI95% = 0.06-0.81) for developing HBC. To BC, there was association with the genotype 2R/3R (OR: 3.79, CI95% = 2.03-7.08).
Our results show relation to the development of BC in association with the analyzed polymorphisms.
乳腺癌（BC）是一种遗传性疾病，其特征是乳腺细胞无序生长和增殖。在巴西，每年约有49240例新的乳腺癌病例。乳腺癌的病因仍知之甚少。乳腺癌可分为散发性（SBC）或遗传性（HBC）。最近的研究将基因多态性与乳腺癌相关联，例如胸苷酸合成酶基因（TYMS）的改变，这些改变可用于改善疾病的诊断和预防。TYMS基因5'-UTR区域的多态性通常呈现重复双倍（2R）和/或重复三倍（3R）。研究表明，与2R/2R基因型相比，纯合3R/3R过度表达，这些多态性变异可能导致个体对乳腺癌发生的易感性。在此背景下，本研究的目的是评估TYMS 2R和3R多态性的频率，比较SBC和HBC患者的基因型和等位基因分布。
本研究共纳入204名受试者，70名乳腺癌患者（33名SBC患者和37名HBC患者）以及134名健康受试者（对照组）。采用聚合酶链反应方法。
结果显示，在乳腺癌、SBC和HBC组中3R等位基因频率较高。BC组中2R/3R基因型频率显著更高。这项研究表明，2R/3R变异（OR = 4.14，CI95% = 1.77 - 9.71）与SBC的发生相关，而2R/2R（OR = 0.233，CI95% = 1.63 - 7.65）和2R/3R（OR = 3.53，CI95% = 0.06 - 0.81）与HBC的发生相关。对于乳腺癌，与2R/3R基因型相关（OR：3.79，CI95% = 2.03 - 7.08）。
我们的结果表明，所分析的多态性与乳腺癌的发生有关。
