Association between Toll-like receptor 2 rs4696483 and rs1898830 polymorphisms and the risk of triple-negative breast cancer

Abstract

Purpose Breast cancer (BC) is heterogeneous in clinical manifestation, of which the triple-negative (TNBC) subtype is the most aggressive. This study examines the associations between Toll-Like Receptor (TLR)-2 polymorphisms and the susceptibility to BC and TNBC. Methods Genotyping of TLR-2 rs1898830 and rs4696483 polymorphisms was done by real-time PCR in 488 women with BC (130 TNBC, 358 non-TNBC) and 476 cancer-free control women. Results The minor allele frequency (MAF) of rs4696483 was significantly lower in BC cases compared to controls, and significantly lower frequencies of rs4696483 C/T and higher frequencies of rs1898830 G/G genotypes were seen in BC cases. Significantly higher MAF of rs4696483 and higher C/T and T/T rs4696483 genotypes frequencies were seen in TNBC than in non-TNBC cases. Considering the prevalent AC haplotype as a reference, 2-locus TLR-2 haplotype analysis did not identify any 2-locus TLR-2 haplotype associated with an altered risk of BC or TNBC. Positive associations of rs1898830 and rs4966483 were seen with the histological type in TNBC and negatively with distant metastasis and HR status in TNBC and non-TNBC rs1898830 carriers. In addition, rs4696483 was positively correlated with hormonotherapy and surgery in non-TNBC cases, while rs1898830 was negatively associated with hormonotherapy. Furthermore, rs1898830 was negatively and positively correlated with BMI in TNBC and TNBC cases, respectively, but positively with Ki-67 status. Conclusions Our study highlights the association between TLR-2 genetic polymorphisms and BC and TNBC susceptibility, suggesting these variants' diagnostic/prognostic capacity in BC patients and patient subgroups.