Abstract
BackgroundToll-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.MethodsIn this prospective observational study, rs3775291 in TLR3 and rs4833095 in TLR1 were genotyped in 715 patients with primary breast cancer in a Chinese population.ResultsUnivariate 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.ConclusionOur 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.
Highlights
Breast cancer is the most frequently diagnosed type of cancer [1], and the risk of recurrence is influenced by the stage at initial presentation and the underlying biology of the tumor
Univariate analysis revealed that the patients with the AA genotype of rs3775291 had a shorter relapse-free survival (RFS) compared with those carrying the G allele in the recessive model (P
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
Summary
Breast cancer is the most frequently diagnosed type of cancer [1], and the risk of recurrence is influenced by the stage at initial presentation and the underlying biology of the tumor. Toll-like receptors (TLRs) play important roles in the innate and adaptive immune responses. They selectively recognize a variety of conserved molecular structures in invading pathogens, initiating complex downstream signaling pathways, including the NF-κB and MAPK pathways, resulting in a cytokine profile that is associated with immune tolerance and cancer progression [5,6,7]. Several lines of evidence have indicated that TLR3 plays important roles in breast cancer development and progression. Treatment with double-stranded RNA (dsRNA) has been shown to be associated with a significant decrease in the risk of relapse in TLR3-positive breast cancer [10]. Toll-like receptors (TLRs) regulate the balance between the innate and adaptive immune responses. 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.
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