Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA.
Eur J Cancer Prev. 2011 Mar;20(2):86-95. doi: 10.1097/CEJ.0b013e3283429e45.
Chemopreventive dietary compounds, such as flavonols, may inhibit colorectal carcinogenesis partly by altering cytokine expression and attenuating inflammation. Single nucleotide polymorphisms (SNPs) in the promoter regions of genes encoding cytokines may influence flavonol-induced changes in cytokine expression and consequently cancer risk. Using logistic regression, we estimated odds ratios (OR) and 95% confidence intervals (CI) for the association between SNPs of interleukin (IL)-1β, 6, 8, and 10 alone or combined with flavonol intake or serum IL concentration changes, and adenoma recurrence in 808 participants from the intervention arm of the Polyp Prevention Trial, a 4-year intervention study evaluating the effectiveness of a low-fat, high-fiber, high-fruit and vegetable diet on adenoma recurrence. Overall, SNPs in genes encoding IL-1β, 6, 8, and 10 were not associated with their corresponding serum concentrations or adenoma recurrence. However, individuals homozygous for IL-10 -592 C (OR=2.23, 95% CI: 1.07-4.66, P(interaction)=0.03) orIL-10 -819 C (OR=2.18, 95% CI: 1.05-4.51, P(interaction)=0.05) had an elevated risk of high-risk adenoma recurrence when their serum IL-10 concentrations increased during the trial. In addition, IL-6 -174 GG in combination with above median flavonol intake (OR=0.14, 95% CI: 0.03-0.66) or with decreased IL-6 concentrations (OR=0.14, 95% CI: 0.03-0.65) reduced the risk of advanced adenoma recurrence, although the interaction term was not statistically significant. In conclusion, our results suggest that IL SNPs, in combination with a flavonol-rich diet or decreased serum IL, may lower the risk of adenoma recurrence.
化学预防膳食化合物,如类黄酮,可能通过改变细胞因子表达和减轻炎症部分抑制结直肠肿瘤发生。细胞因子编码基因启动子区域的单核苷酸多态性(SNP)可能影响类黄酮诱导的细胞因子表达变化,并因此影响癌症风险。我们使用逻辑回归,估计了白细胞介素(IL)-1β、6、8 和 10 的 SNP 与单独或与类黄酮摄入或血清 IL 浓度变化相结合,以及与腺瘤复发的关联的优势比(OR)和 95%置信区间(CI)在 808 名来自干预组的参与者中,干预组来自预防息肉试验的干预臂,这是一项为期 4 年的干预研究,评估低脂、高纤维、高水果和蔬菜饮食对腺瘤复发的有效性。总体而言,编码 IL-1β、6、8 和 10 的基因中的 SNP 与它们相应的血清浓度或腺瘤复发无关。然而,IL-10-592 C 纯合子(OR=2.23,95%CI:1.07-4.66,P(交互)=0.03)或 IL-10-819 C (OR=2.18,95%CI:1.05-4.51,P(交互)=0.05)的个体在试验期间血清 IL-10 浓度升高时,患高危腺瘤复发的风险增加。此外,IL-6-174 GG 与中位数以上的类黄酮摄入(OR=0.14,95%CI:0.03-0.66)或与降低的 IL-6 浓度(OR=0.14,95%CI:0.03-0.65)相结合降低了晚期腺瘤复发的风险,尽管交互项没有统计学意义。总之,我们的结果表明,IL SNP 与富含类黄酮的饮食或降低血清 IL 相结合,可能降低腺瘤复发的风险。