title: A Prospective Evaluation of the Association between a Single Nucleotide Polymorphism rs3775291 in Toll-Like Receptor 3 and Breast Cancer Relapse.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of General Surgery, Affiliated Union Hospital, Fujian Medical University, Fuzhou, China; Department of Breast Surgery, Key Laboratory of Breast Cancer, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Dan-Na
authors.initials: DN
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Affiliated Union Hospital, Fujian Medical University, Fuzhou, China.
authors.forename: Chuan-Gui
authors.initials: CG
authors.lastname: Song
authors.affiliation: Department of Breast Surgery, Key Laboratory of Breast Cancer, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Ke-Da
authors.initials: KD
authors.lastname: Yu
authors.affiliation: Department of Breast Surgery, Key Laboratory of Breast Cancer, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Yi-Zhou
authors.initials: YZ
authors.lastname: Jiang
authors.affiliation: Department of General Surgery, Affiliated Union Hospital, Fujian Medical University, Fuzhou, China.
authors.forename: Fu-Gui
authors.initials: FG
authors.lastname: Ye
authors.affiliation: Department of Breast Surgery, Key Laboratory of Breast Cancer, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Shao
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D002681:China / Q000453:epidemiology; D018572:Disease-Free Survival; D005260:Female; D005799:Genes, Dominant; D005808:Genes, Recessive; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D008957:Models, Genetic; D020125:Mutation, Missense; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D051194:Toll-Like Receptor 1 / Q000235:genetics; D051196:Toll-Like Receptor 3 / Q000235:genetics*; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000401:mortality
chemical_list: D014408:Biomarkers, Tumor; C495344:TLR3 protein, human; D051194:Toll-Like Receptor 1; D051196:Toll-Like Receptor 3