Gunter Marc J, Canzian Federico, Landi Stefano, Chanock Stephen J, Sinha Rashmi, Rothman Nathaniel
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, USA.
Cancer Epidemiol Biomarkers Prev. 2006 Jun;15(6):1126-31. doi: 10.1158/1055-9965.EPI-06-0042.
Chronic inflammation has been reported to be a risk factor for colorectal neoplasia. The propensity to mount an inflammatory response is modified by germ line variation in cytokine and other inflammation-related genes. We hypothesized that a proinflammatory genotype would be positively associated with colorectal adenoma, a precursor of colorectal cancer. We investigated the association of colorectal adenoma with 19 single nucleotide polymorphisms in a range of important proinflammatory (IL1B, IL6, IL8, TNF, and LTA) and anti-inflammatory (IL4, IL10, and IL13) cytokines and other inflammation-related genes (PTGS2 and PPARG) in a case-control study of risk factors for colorectal polyps in which all participants (ages 18-74 years) had undergone colonoscopy or sigmoidoscopy. The study sample comprised 244 cases of colorectal adenoma and 231 polyp-free controls. Compared with being homozygous for the common allele, heterozygosity at the IL1B -31 (C>T) locus was associated with an odds ratio (OR) for colorectal adenoma of 1.8 [95% confidence interval (95% CI), 1.2-2.9]. Homozygous carriers of the IL8 -251-A allele were at 2.7-fold increased risk of adenoma (95% CI, 1.5-4.9) compared with homozygosity for the common T allele, whereas carriage of at least one IL8 -251-A allele conferred a 1.5 increased odds of disease (95% CI, 1.0-2.4). Among non-nonsteroidal anti-inflammatory drug users, there was a statistically significant association between the IL10 -819-T/T genotype and adenoma compared with the common IL10 -819-C/C genotype (OR, 3.9; 95% CI, 1.1-13.6), which was not evident among nonsteroidal anti-inflammatory drug users (OR, 0.7; 95% CI, 0.3-1.5; P(interaction) = 0.01). These exploratory data provide evidence that polymorphic variation in genes that regulate inflammation could alter risk for colorectal adenoma.
据报道，慢性炎症是结直肠肿瘤的一个风险因素。细胞因子及其他炎症相关基因的种系变异会改变引发炎症反应的倾向。我们推测促炎基因型与结直肠腺瘤（结直肠癌的前体）呈正相关。在一项针对结直肠息肉风险因素的病例对照研究中，我们调查了19个单核苷酸多态性与结直肠腺瘤的关联，这些多态性存在于一系列重要的促炎细胞因子（白细胞介素1β、白细胞介素6、白细胞介素8、肿瘤坏死因子和淋巴毒素α）、抗炎细胞因子（白细胞介素4、白细胞介素10和白细胞介素13）以及其他炎症相关基因（环氧化酶-2和过氧化物酶体增殖物激活受体γ）中，研究中的所有参与者（年龄在18 - 74岁）均接受过结肠镜检查或乙状结肠镜检查。研究样本包括244例结直肠腺瘤病例和231例无息肉对照。与常见等位基因的纯合子相比，白细胞介素1β -31（C>T）位点的杂合性与结直肠腺瘤的优势比（OR）为1.8 [95%置信区间（95%CI），1.2 - 2.9]。白细胞介素8 -251 -A等位基因的纯合携带者患腺瘤的风险比常见T等位基因的纯合子高2.7倍（95%CI，1.5 - 4.9），而携带至少一个白细胞介素8 -251 -A等位基因使患病几率增加1.5倍（95%CI，1.0 - 2.4）。在非非甾体抗炎药使用者中，白细胞介素10 -819 -T/T基因型与腺瘤之间存在统计学上的显著关联，与常见的白细胞介素10 -819 -C/C基因型相比（OR，3.9；95%CI，1.1 - 13.6），而在非甾体抗炎药使用者中这种关联不明显（OR，0.7；95%CI，0.3 - 1.5；交互作用P值 = 0.01）。这些探索性数据提供了证据，表明调节炎症的基因中的多态性变异可能会改变患结直肠腺瘤的风险。
