TLR8 and TLR9 gene polymorphisms and the risk of high-grade serous ovarian cancer
High-grade serous ovarian carcinoma (HGSOC) is the most prevalent and lethal histotype of epithelial ovarian cancer (EOC). Single nucleotide polymorphisms (SNPs) in Toll-like receptor (TLR) genes may serve as important markers of susceptibility to numerous cancers. We explored the frequency of TLR8 and TLR9 polymorphisms in 325 women and determined their role in susceptibility to EOC and viral infection. The group of patients with EOC included 93 HGSOC and 32 non-HGSOC cases. TLR8 rs3764879, TLR8 rs3764880, TLR9 rs352139, and rs352140 SNPs were genotyped using the allelic discrimination method. The homozygous recessive genotypes for TLR8 rs3764879 and TLR9 rs352139 SNPs were more common in patients with EOC, compared to healthy women, and increased the risk of ovarian cancer (p = 0.0001 and p < 0.05, respectively). The TLR8 rs3764879 SNP reached statistical significance after Bonferroni's correction for multiple tests. The homozygous recessive genotype for TLR8 rs3764879 (-129C>G) was associated with a five-fold increased risk of HGSOC (p = 0.0001). A mutation in at least one allele of the TLR8 rs3764879 was also associated with a higher level of TLR8 expression in tumor tissues (p = 0.0008). The present study demonstrated a strong association between the TLR8 -129C>G SNP and an increased risk of the HGSOC subtype.