Novel sequence variants in the TLR6 gene associated with advanced breast cancer risk in the Saudi Arabian population

• Published in: PloS one 2018-11, Vol.13 (11), p.e0203376-e0203376
• Main Authors: Semlali, Abdelhabib, Almutairi, Mikhlid, Rouabhia, Mahmoud, Reddy Parine, Narasimha, Al Amri, Abdullah, S Al-Numair, Nouf, M Hawsawi, Yousef, Saud Alanazi, Mohammad
• Format: Article
• Language: English
• Subjects: Age; Alleles; Biochemistry; Biology and Life Sciences; Biomarkers; Breast cancer; Breast Neoplasms - epidemiology; Breast Neoplasms - genetics; Cancer; Case-Control Studies; Cytokines; Diagnostic systems; Estrogen receptors; Estrogens; Female; Females; Gastroenterology; Gene Frequency; Genes; Genetic Predisposition to Disease; Genomes; Genomics; Genotype; Health risks; Hospitals; Humans; Medicine and Health Sciences; Middle Aged; Models, Molecular; Mutation; Patients; People and Places; Polymorphism, Single Nucleotide; Population genetics; Prostate cancer; Protective structures; Proteins; Research and Analysis Methods; Risk; Saudi Arabia - epidemiology; Single-nucleotide polymorphism; Studies; Toll-Like Receptor 6 - chemistry; Toll-Like Receptor 6 - genetics; Toll-like receptors; Womens health
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0203376

Herein, we evaluated the association of the Toll-like receptor 6 (TLR6) single nucleotide polymorphisms (SNPs) rs3796508 (Val327Met) and rs5743810 (Ser249Pro) with breast cancer (BC) susceptibility in Saudi Arabian women, using in silico analysis. We found no significant differences in genotypic and allelic frequencies for rs3796508 between the BC patients (n = 127) and healthy individuals (n = 116). However, 86% of the BC patients, versus 98% of the healthy controls, carried the rs5743810 Pro allele (OR = 0.103, CI = 0.036-0.293, P = 0.00001). Advanced analysis based on the comparison of the estrogen receptor (ER)-positive and -negative patients with the healthy controls indicated a significant association between rs5743810 allelic frequency and BC risk protection (OR = 0.100, CI = 0.034-0.297, P = 0.00001 for ER+ BC cases; OR = 0.102, CI = 0.033-0.318, P = 0.00001 for ER-BC cases). Furthermore, rs5743810 was associated with BC risk protection at either above or below 48 years of age at diagnosis (OR = 0.101, CI = 0.022-0.455, P = 0.00037 for age ≤48 years; OR = 0.120, CI = 0.028-0.519, P = 0.00087 for age >48 years). Such associations were not found for rs3796508. In silico analysis indicated that these SNPs had neutral effects within the TLR6 structure, confirming the protective role of rs5743810. Our findings therefore suggest a strong association between rs5743810 and protection against BC risk in Saudi Arabian women. Importantly, the rs5743810 Pro allele could be a potential BC diagnostic biomarker in this ethnic population.