Research Papers:

Polymorphisms in TIM-3 and breast cancer susceptibility in Chinese women: A case-control study

Zheng Wang _, Xinghan Liu, Xijing Wang, Tie Chong, Shuai Lin, Meng Wang, Xiaobin Ma, Kang Liu, Peng Xu, Yanjing Feng and Zhijun Dai

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Oncotarget. 2016; 7:43703-43712. https://doi.org/10.18632/oncotarget.9665

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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

Correspondence to:

Zhijun Dai, email: dzj0911@126.com; dzj0911@mail.xjtu.edu.cn

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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