A Prospective Evaluation of the Association between a Single Nucleotide Polymorphism rs3775291 in Toll-Like Receptor 3 and Breast Cancer Relapse

PLoS One. 2015 Jul 30;10(7):e0133184. doi: 10.1371/journal.pone.0133184. eCollection 2015.

Abstract

Background: Toll-like receptors (TLRs) regulate the balance between the innate and adaptive immune responses. Missense single nucleotide polymorphisms (SNPs) in TLRs might be functional and thus influence the risks of chronic infection and cancer development. Here, we investigated the association of two missense SNPs, rs3775291 (c.1234G>A) in the TLR3 gene and rs4833095 (c.743T>C) in the TLR1 gene, with relapse-free survival (RFS) in a cohort of prospectively observed breast cancer patients.

Methods: In this prospective observational study, rs3775291 in TLR3 and rs4833095 in TLR1 were genotyped in 715 patients with primary breast cancer in a Chinese population.

Results: Univariate analysis revealed that the patients with the AA genotype of rs3775291 had a shorter RFS compared with those carrying the G allele in the recessive model (P<0.01), but this finding was not observed with the dominant model (P = 0.31). The results remained significant after adjusting for the clinical parameters in the recessive model (HR = 3.53, 95% confidence interval [CI]: 1.98-6.31, P<0.01). Further survival analysis indicated that this SNP was significant in the luminal-B, triple-negative breast cancer (TNBC), and human epidermal growth factor receptor 2-positive (HER2+) patients using the recessive model but that it was not significant in the luminal-A patients. The SNP rs4833095 showed a non-significant tendency toward an increased RFS rate in the patients with the TT genotype.

Conclusion: Our results suggest that the SNP rs3775291 in TLR3 may influence patient outcome. Further studies with larger sample sizes should be conducted to validate our findings.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Asian People / genetics
  • Biomarkers, Tumor / genetics
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality
  • China / epidemiology
  • Disease-Free Survival
  • Female
  • Genes, Dominant
  • Genes, Recessive
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Models, Genetic
  • Mutation, Missense
  • Neoplasm Recurrence, Local / genetics
  • Polymorphism, Single Nucleotide*
  • Prospective Studies
  • Toll-Like Receptor 1 / genetics
  • Toll-Like Receptor 3 / genetics*
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / mortality

Substances

  • Biomarkers, Tumor
  • TLR3 protein, human
  • Toll-Like Receptor 1
  • Toll-Like Receptor 3

Grants and funding

This work was supported by the Natural Science Foundation of Fujian, China (2012J01357) (for CGS); the Training Plan of Middle-aged and Young Talents of Fujian Province Health and Family Planning Commission (2014-ZQN-ZD-10) (for CGS); the National Natural Science Foundation of China (81370075, 81001169); the Training Plan of Excellent Talents in Shanghai Municipality Health System (for KDY.); the Research and Innovation Project of Shanghai Municipal Education Commission (2014, for KDY.); the Shanghai International Science and Technique Cooperation Foundation (12410707700); the International S&T Cooperation Program of China (ISTCP No. 09); and Shanghai Committee of Science and Technology Funds (12DZ2260100). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.