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

Oncotarget. 2016 Jul 12;7(28):43703-43712. doi: 10.18632/oncotarget.9665.

Abstract

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.

Keywords: TIM-3; breast cancer; case-control study; polymorphism.

MeSH terms

  • Adult
  • Aged
  • Asian People / genetics
  • Breast Neoplasms / genetics*
  • Case-Control Studies
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Hepatitis A Virus Cellular Receptor 2 / genetics*
  • Humans
  • Middle Aged
  • Polymorphism, Single Nucleotide

Substances

  • HAVCR2 protein, human
  • Hepatitis A Virus Cellular Receptor 2