Gutierrez-Rubio S A, Quintero-Ramos A, Durán-Cárdenas A, Franco-Topete R A, Castro-Cervantes J M, Oceguera-Villanueva A, Jiménez-Pérez L M, Balderas-Peña L M A, Morgan-Villela G, Del-Toro-Arreola A, Daneri-Navarro A
Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Colonia Independencia, Guadalajara, Jalisco, Mexico.
UMAE Hospital de Especialidades del Centro Médico Nacional de Occidente del IMSS Hospital de Especialidades, Instituto Mexicano del Seguro Social, Guadalajara, Mexico.
Genet Mol Res. 2015 Feb 13;14(1):1250-9. doi: 10.4238/2015.February.13.3.
MDR1, which is encoded by the ABCB1 gene, is involved in multidrug resistance (hydrophobic), as well as the elimination of xenotoxic agents. The association between ABCB1 gene polymorphisms and breast cancer risk in different populations has been described previously; however, the results have been inconclusive. In this study, we examined the association between polymorphisms 3435 C/T and 1236 C/T in the ABCB1 gene and breast cancer development in Mexican women according to their menopausal status and molecular classification. Molecular subtypes as well as allele and genotype frequencies were analyzed. A total of 248 women with initial breast cancer diagnosis and 180 ethnically matched, healthy, unrelated individuals were enrolled. Polymerase chain reaction-restriction fragment length polymorphism was performed to detect polymorphisms 3435 C/T and 1236 C/T in the ABCB1 gene. Premenopausal T allele carriers of the 3435 C/T polymorphism showed a 2-fold increased risk of breast cancer with respect to the reference and postmenopausal groups, as well as triple-negative expression regarding the luminal A/B molecular subrogated subtypes. In contrast, the CT genotype of the 1236 polymorphism was a protective factor against breast cancer. We conclude that the T allele carrier of the 3435 C/T polymorphism in the ABCB1 gene in combination with an estrogen receptor-negative status may be an important risk factor for breast cancer development in premenopausal women.
由ABCB1基因编码的多药耐药蛋白1（MDR1）参与多药耐药（疏水性）以及外源性毒性物质的清除。先前已描述了不同人群中ABCB1基因多态性与乳腺癌风险之间的关联；然而，结果尚无定论。在本研究中，我们根据墨西哥女性的绝经状态和分子分类，研究了ABCB1基因中3435 C/T和1236 C/T多态性与乳腺癌发生之间的关联。分析了分子亚型以及等位基因和基因型频率。共纳入248例初诊为乳腺癌的女性和180例种族匹配、健康、无亲缘关系的个体。采用聚合酶链反应-限制性片段长度多态性方法检测ABCB1基因中的3435 C/T和1236 C/T多态性。3435 C/T多态性的绝经前T等位基因携带者相对于参照组和绝经后组，患乳腺癌的风险增加了2倍，相对于管腔A/B分子亚型，三阴性表达增加。相比之下，1236多态性的CT基因型是预防乳腺癌的一个保护因素。我们得出结论，ABCB1基因中3435 C/T多态性的T等位基因携带者与雌激素受体阴性状态相结合，可能是绝经前女性患乳腺癌的一个重要风险因素。
