Wang Zheng, Liu Xinghan, Wang Xijing, Chong Tie, Lin Shuai, Wang Meng, Ma Xiaobin, Liu Kang, Xu Peng, Feng Yanjing, Dai Zhijun
Department of Oncology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
Department of Medical Oncology, Xi'an Central Hospital, Xi'an 710004, China.
Oncotarget. 2016 Jul 12;7(28):43703-43712. doi: 10.18632/oncotarget.9665.
Previous studies have found associations between polymorphisms in T cell immunoglobulin and mucin domain 3 (TIM-3) and increased risks of various cancers. However, the association between TIM-3 polymorphisms and breast cancer (BC) remains uncertain. In this study, a total of 560 BC patients and 583 age, sex, and ethnicity-matched healthy controls from Northwest China were included. The polymorphisms were genotyped using Sequenom MassARRAY. The expression level of TIM-3 protein was detected by immunohistochemistry. We observed rs10053538 had a significantly increased risk of BC, comparing with the wild-type genotype even after Bonferroni correction. In addition, the rs4704853 G>A variants were more frequent among BC patients than the controls (GA + AA vs. GG: OR = 1.32, 95% CI = 1.03-1.69, P = 0.026); However, the significance was lost after Bonferroni correction (P = 0.078). Furthermore, rs10053538 was associated with lymph node metastasis. Age stratification revealed that among patients aged <49 years, those with the rs4704853 GA/AA genotype had a higher risk of BC; But there was no difference when Bonferroni correction was conducted. Immunohistochemical analysis showed that the expression of TIM-3 protein in the breast cancer tissues was higher in patients carrying the rs10053538 GT+TT genotype than those with GG genotype (P = 0.012). However, we failed to find any difference between BC patients and controls in any rs1036199 genetic model. These findings suggested that rs10053538 in TIM-3 might increase susceptibility to BC and promote the progression of BC in Chinese women.
先前的研究发现,T细胞免疫球蛋白和粘蛋白结构域3(TIM-3)的多态性与多种癌症风险增加之间存在关联。然而,TIM-3多态性与乳腺癌(BC)之间的关联仍不确定。在本研究中,纳入了来自中国西北的560例BC患者以及583例年龄、性别和种族相匹配的健康对照。使用Sequenom MassARRAY对多态性进行基因分型。通过免疫组织化学检测TIM-3蛋白的表达水平。我们观察到,即使经过Bonferroni校正,与野生型基因型相比,rs10053538患BC的风险仍显著增加。此外,rs4704853 G>A变异在BC患者中比在对照中更常见(GA + AA与GG相比:OR = 1.32,95% CI = 1.03 - 1.69,P = 0.026);然而,经过Bonferroni校正后,该显著性消失(P = 0.078)。此外,rs10053538与淋巴结转移相关。年龄分层显示,在年龄<49岁的患者中,携带rs4704853 GA/AA基因型的患者患BC的风险更高;但进行Bonferroni校正后没有差异。免疫组织化学分析表明,携带rs10053538 GT+TT基因型的乳腺癌组织中TIM-3蛋白的表达高于携带GG基因型的患者(P = 0.012)。然而,在任何rs1036199遗传模型中,我们均未发现BC患者与对照之间存在任何差异。这些发现表明,TIM-3中的rs10053538可能会增加中国女性患BC的易感性并促进BC的进展。