Abdelhabib Semlali,1 Narasimha Reddy Parine,1 Abdullah Al Amri,1 Arezki Azzi,2 Maha Arafah,3 Muhammad Kohailan,1 Jilani P Shaik,1 Majid Abdulrahman Almadi,4,5 Abdulrahman M Aljebreen,3,4 Othman Alharbi,3,4 Nahla Ali Azzam,3,4 Mahmoud Rouabhia,6 Mohammad Saud Alanazi1 1Genome Research, Department of Biochemistry, College of Sciences, King Saud University, 2College of Medicine, Al Imam Muhammad Ibn Saud Islamic University, 3College of Medicine, King Saud University, 4Division of Gastroenterology, King Khalid University Hospital, King Saud University, Riyadh, Kingdom of Saudi Arabia; 5Division of Gastroenterology, McGill University Health Center, Montreal General Hospital, Montreal, 6Groupe de Recherche en Écologie Buccale, Département de Stomatologie, Faculté de Médecine Dentaire, Université Laval, Québec City, QC, Canada Objective: The authors aimed to explore the relationship between the expression/polymorphisms of TLR-9 and susceptibility to colon cancer development in the Saudi Arabian population. Methods: In total, blood samples from 115 patients with colon cancer and 102 participants without colon cancer were analyzed in this study. Three single-nucleotide polymorphisms (SNPs) were selected from the TLR-9 gene, including two sites within the TLR-9 gene’s promoter region (rs352144 and rs187084) and one site in a TLR-9 intron region (rs5743839). Odds ratios (ORs) and 95% confidence intervals (CIs) were computed from logistic regression models after adjusting for age, gender, and tumor localization. To investigate the differential expression of TLR-9 in colon cancer, TLR-9 expression was evaluated using quantitative real-time reverse transcription polymerase chain reaction on 40 matched normal and colon tissues. Results: The authors found that TLR-9 expression was decreased in colon cancer tissues as compared with that in normal tissues. Moreover, significant associations between the TLR-9 rs187084 SNP and colon cancer risk were observed in female patients only. In rs187084, the T allele had a significantly lower frequency (2.8 times) in female cancer patients than in controls (0.27 vs 0.41). The TLR-9 rs352139 and rs352144 SNPs were significantly associated with colon cancer development when the tumor was located in the rectal area. Conclusion: The findings support the hypothesis that TLR-9 has an anticancer role in colon cancer development. Furthermore, genetic variation may influence colon cancer development, and SNPs in TLR-9 could serve as biomarkers for decision making in the treatment of females with rectal cancer. Keywords: Innate, immunity, TLR polymorphisms, rs187084, rs352139, rs352144
