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

<div><p>Background</p><p>Toll-like receptors (TLRs) regulate the balance between the innate and adaptive immune responses. Missense single nucleotide polymorphisms (SNPs) in <i>TLRs</i> 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 <i>TLR3</i> gene and rs4833095 (c.743T>C) in the <i>TLR1</i> gene, with relapse-free survival (RFS) in a cohort of prospectively observed breast cancer patients.</p><p>Methods</p><p>In this prospective observational study, rs3775291 in <i>TLR3</i> and rs4833095 in <i>TLR1</i> were genotyped in 715 patients with primary breast cancer in a Chinese population.</p><p>Results</p><p>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.</p><p>Conclusion</p><p>Our results suggest that the SNP rs3775291 in <i>TLR3</i> may influence patient outcome. Further studies with larger sample sizes should be conducted to validate our findings.</p>