Centre for Colorectal Disease, St. Vincent's University Hospital, Dublin, Ireland.
Department of Colorectal Surgery, Beaumont Hospital, Dublin, Ireland.
Colorectal Dis. 2021 May;23(5):1043-1048. doi: 10.1111/codi.15550. Epub 2021 Feb 24.
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.
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.
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.
These data do not support an association between polymorphisms in smad7, TLR2 or TLR4 and the development of UC-associated colorectal cancer.
溃疡性结肠炎（UC）的特征是慢性黏膜炎症和结直肠癌风险增加。smad7、TLR2 和 TLR4 调节肠道炎症，其多态性影响散发性结直肠癌的发展风险。本研究旨在探讨 smad7、TLR2 和 TLR4 单核苷酸多态性（SNPs）与 UC 患者结直肠癌发展之间的关系。
从 1985 年至 2013 年间接受全结肠直肠切除术的 90 例 UC 患者（30 例 UC 相关结直肠癌患者和 60 例对照 UC 患者）的福尔马林固定、石蜡包埋组织中提取 DNA。对照病例按结肠炎诊断年龄、疾病持续时间和性别与病例 2:1 匹配。对 smad7 rs4464148、rs11874392、rs12953717 和 rs4939827 SNPs、TLR2 rs5743704 和 rs5743708 SNPs 以及 TLR4 rs4986790 和 rs4986791 SNPs 进行基因分型。
90 例患者中有 63 例（70%）为男性，UC 诊断时的平均年龄为 38.6±1.6 岁。UC 相关结直肠癌的诊断时间平均为 13.5±1.9 年。5 年无复发生存率和癌症特异性生存率分别为 76%和 88%。所有 8 个 SNP 均处于 Hardy-Weinberg 平衡状态。smad7、TLR2 或 TLR4 中评估的 8 个 SNP 均未在等位基因或基因型水平上与 UC 相关结直肠癌的发生相关。
这些数据不支持 smad7、TLR2 或 TLR4 多态性与 UC 相关结直肠癌发展之间的关联。
