Polymorphisms in TIM-3 and breast cancer susceptibility in Chinese women: A case-control study
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Zheng Wang1,2, Xinghan Liu1, Xijing Wang1, Tie Chong3, Shuai Lin1, Meng Wang1, Xiaobin Ma1, Kang Liu1, Peng Xu1, Yanjing Feng1, Zhijun Dai1
1Department of Oncology, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
2Department of Medical Oncology, Xi’an Central Hospital, Xi’an 710004, China
3Department of Urologic Surgery, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
Keywords: TIM-3, breast cancer, polymorphism, case-control study
Received: December 22, 2015 Accepted: May 12, 2016 Published: May 27, 2016
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.
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