Journal
COLORECTAL DISEASE
Volume 23, Issue 5, Pages 1043-1048Publisher
WILEY
DOI: 10.1111/codi.15550
Keywords
Ulcerative colitis; colorectal cancer; phenotype; smad7; TLR2; TLR4; single nucleotide polymorphism
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The study investigated the association between SNPs in smad7, TLR2, and TLR4 and the development of UC-associated colorectal cancer in 90 patients with UC. The results showed that none of the eight SNPs in smad7, TLR2, or TLR4 were associated with the development of UC-associated colorectal cancer at allelic or genotypic level.
Aim Ulcerative colitis (UC) is characterized by chronic mucosal inflammation and an increased risk of colorectal cancer. smad7, TLR2 and TLR4 modulate intestinal inflammation and their polymorphisms affect the risk of development of sporadic colorectal cancer. The aim of the current study was to examine the association between single nucleotide polymorphisms (SNPs) in smad7, TLR2 and TLR4 and the development of colorectal cancer in patients with UC. Method DNA was extracted from formalin-fixed, paraffin-embedded tissue from 90 patients with UC who had undergone panproctocolectomy between 1985 and 2013 (30 with UC-associated colorectal cancer and 60 control UC patients). Control cases were matched 2:1 for age at diagnosis of colitis, duration of disease and gender. Genotyping was performed for the smad7 rs4464148, rs11874392, rs12953717 and rs4939827 SNPs, the TLR2 rs5743704 and rs5743708 SNPs and the TLR4 rs4986790 and rs4986791 SNPs. Results Sixty three of the 90 patients (70%) were men and the mean age at diagnosis of UC was 38.6 +/- 1.6 years. The mean time to the diagnosis of UC-associated colorectal cancer was 13.5 +/- 1.9 years. The 5-year recurrence-free and cancer-specific survival rates were 76% and 88%, respectively. All eight SNPs were in Hardy-Weinberg equilibrium. None of the eight SNPs assessed in smad7, TLR2 or TLR4 were associated with the development of UC-associated colorectal cancer at an allelic or genotypic level. Conclusions These data do not support an association between polymorphisms in smad7, TLR2 or TLR4 and the development of UC-associated colorectal cancer.
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