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

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.

Tim-3 finds its place in the cancer immunotherapy landscape

“…83 TIM-3-574 G/T polymorphism has shown association with the risk of developing myasthenia gravis-associated thymoma 84 and TIM-3-1516 G/T has shown association with increased breast cancer susceptibility and breast cancer progression. 85 Further, two recent studies demonstrate that germline loss-of-function mutations in HAVCR2 lead to a hyperactivation of T and myeloid cells resulting in two inflammatory diseases, HLH and SPTCL. 6 7 The mutations are located in the Tim-3 IgV domain and result in misfolding of Tim-3 protein.…”

Beyond PD-1/PD-L1 Inhibition: What the Future Holds for Breast Cancer Immunotherapy

“…Burugu et al evaluated TIM-3 IHC expression in 3992 BC samples of all subtypes and found that the TIM-3 intraepithelial TIL infiltration is associated with a better outcome [32]. TIM-3 polymorphisms might also play a role in the susceptibility to, and prognosis of BC [101,102,103].…”

IL-18 polymorphisms contribute to hepatitis B virus-related cirrhosis and hepatocellular carcinoma susceptibility in Chinese population: a case-control study

“…The samples were centrifugated and stored in −80°C freezers for long-term storage. The genomic DNA was extracted and concentrated by the method described in our previous studies [ 48 , 49 ]. Two tag-SNPs (rs187238 and rs1946518) were selected in this study.…”