Polymorphism of the cyclin D1 gene, CCND1, and risk for incident sporadic colorectal adenomas.
Polymorphism of the cyclin D1 gene, CCND1, and risk for incident sporadic colorectal adenomas.
复制标题
DOI：
--
复制
发表时间：
2003-12
期刊：
影响因子：
11.2
通讯作者：
Ryan Lewis;R. Bostick;D. Xie;Z. Deng;M. Wargovich;Michael F. Fina;W. Roufail;K. Geisinger
中科院分区：
文献类型：
--
作者：
Ryan Lewis;R. Bostick;D. Xie;Z. Deng;M. Wargovich;Michael F. Fina;W. Roufail;K. Geisinger
细胞周期蛋白D1由CCND 1基因编码，由腺瘤性息肉病大肠杆菌-β-连环蛋白-T细胞因子/淋巴增强因子途径激活，诱导G（1）期至S期细胞周期转换，促进细胞增殖。最近描述的密码子242，外显子4，G到A单核苷酸多态性（A870 G）产生更长的半衰期细胞周期蛋白D1。为了研究CCND 1基因型是否影响结直肠腺瘤的风险，我们在北卡罗来纳州一项基于结肠镜检查的病例对照研究中，对161例偶发散发性腺瘤病例和213例年龄在30-74岁之间的对照进行了CCND 1基因型的PCR/RFLP检测。在68%的病例和60%的对照中发现至少一个多态性A等位基因。携带A等位基因与腺瘤风险增加相关：年龄和性别调整后的比值比（OR）为1.5 [95%置信区间（CI）1.0-2.4]，这一发现对于多发性腺瘤的患者更为明显（OR 2.9，95% CI 1.4-6.0）、较大（≥ 1 cm; OR 2.4，95% CI 1.2-4.8）、中度至重度异型增生（OR 2.1，95% CI 1.1-3.8）或位于结肠右侧（OR 3.6，95% CI 1.3-10.0）。联合风险因素多变量分析显示，年龄较大的患者与（57岁以上）OR 2.8，95% CI 1.4-5.5），男性（OR 2.8，95% CI 1.3-5.7），目前吸烟（OR 2.7，95% CI 1.3-5.7），或目前饮酒（OR 2.2，95%CI 1.2-4.2），如果他们有一个A等位基因，在使用非甾体抗炎药的患者中有更强的负相关性（OR 0.4，95%CI 0.2-0.9）或钙摄入量较高（OR 0.4，95%CI 0.2-0.9）。这些数据支持CCND 1 A870 G多态性可能增加结直肠肿瘤风险的假设。
Cyclin D1, encoded by the CCND1 gene and activated by the adenomatous polyposis coli-beta-catenin-T-cell factor/lymphoid enhancing factor pathway, induces G(1) to S-phase cell cycle transition, promoting cell proliferation. A recently described codon 242, exon 4, G to A single nucleotide polymorphism (A870G) produces a longer half-life cyclin D1. To investigate whether CCND1 genotype influences risk for colorectal adenoma, we genotyped CCND1 by PCR/RFLP on 161 incident sporadic adenoma cases and 213 controls ages 30-74 years in a North Carolina colonoscopy-based case-control study. At least one polymorphic A allele was found in 68% of cases and 60% of controls. Having an A allele was associated with increased risk for adenoma: the age- and sex-adjusted odds ratio (OR) was 1.5 [95% confidence interval (CI) 1.0-2.4], a finding that was stronger for those whose adenomas were multiple (OR 2.9, 95% CI 1.4-6.0), larger (>or=1 cm; OR 2.4, 95% CI 1.2-4.8), had moderate to severe dysplasia (OR 2.1, 95% CI 1.1-3.8), or were in the right side of the colon (OR 3.6, 95% CI 1.3-10.0). Joint risk factor multivariate analyses revealed stronger positive associations among those who were older (>57 years; OR 2.8, 95% CI 1.4-5.5), male (OR 2.8, 95% CI 1.3-5.7), currently smoked (OR 2.7, 95% CI 1.3-5.7), or currently drank alcohol (OR 2.2, 95% CI 1.2-4.2) if they had an A allele and stronger inverse associations among those who used nonsteroidal anti-inflammatory drugs (OR 0.4, 95% CI 0.2-0.9) or had higher calcium intakes (OR 0.4, 95% CI 0.2-0.9) if they had no A allele. These data support the hypothesis that the CCND1 A870G polymorphism may increase risk for colorectal neoplasms.