Alexander Melannie, Burch James B, Steck Susan E, Chen Chin-Fu, Hurley Thomas G, Cavicchia Philip, Ray Meredith, Shivappa Nitin, Guess Jaclyn, Zhang Hongmei, Youngstedt Shawn D, Creek Kim E, Lloyd Stephen, Yang Xiaoming, Hébert James R
South Carolina Statewide Cancer Prevention and Control Program, University of South Carolina, Columbia, SC, USA.
Center for Molecular Studies, Greenwood Genetic Center, Greenwood, SC, USA.
Oncol Rep. 2015 Feb;33(2):935-41. doi: 10.3892/or.2014.3667. Epub 2014 Dec 11.
Clock genes are expressed in a self-perpetuating, circadian pattern in virtually every tissue including the human gastrointestinal tract. They coordinate cellular processes critical for tumor development, including cell proliferation, DNA damage response and apoptosis. Circadian rhythm disturbances have been associated with an increased risk for colon cancer and other cancers. This mechanism has not been elucidated, yet may involve dysregulation of the 'period' (PER) clock genes, which have tumor suppressor properties. A variable number tandem repeat (VNTR) in the PERIOD3 (PER3) gene has been associated with sleep disorders, differences in diurnal hormone secretion, and increased premenopausal breast cancer risk. Susceptibility related to PER3 has not been examined in conjunction with adenomatous polyps. This exploratory case-control study was the first to test the hypothesis that the 5-repeat PER3 VNTR sequence is associated with increased odds of adenoma formation. Information on demographics, medical history, occupation and lifestyle was collected prior to colonoscopy. Cases (n=49) were individuals with at least one histopathologically confirmed adenoma. Controls (n=97) included patients with normal findings or hyperplastic polyps not requiring enhanced surveillance. Unconditional multiple logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs), after adjusting for potential confounding. Adenomas were detected in 34% of participants. Cases were more likely to possess the 5-repeat PER3 genotype relative to controls (4/5 OR, 2.1; 95% CI, 0.9-4.8; 5/5 OR, 5.1; 95% CI, 1.4-18.1; 4/5+5/5 OR, 2.5; 95% CI, 1.7-5.4). Examination of the Oncomine microarray database indicated lower PERIOD gene expression in adenomas relative to adjacent normal tissue. Results suggest a need for follow-up in a larger sample.
生物钟基因在包括人类胃肠道在内的几乎每一个组织中，都以一种自我维持的昼夜节律模式表达。它们协调对肿瘤发展至关重要的细胞过程，包括细胞增殖、DNA损伤反应和细胞凋亡。昼夜节律紊乱与结肠癌和其他癌症风险增加有关。这种机制尚未阐明，但可能涉及具有肿瘤抑制特性的“周期”（PER）生物钟基因的失调。周期蛋白3（PER3）基因中的可变数目串联重复序列（VNTR）与睡眠障碍、昼夜激素分泌差异以及绝经前乳腺癌风险增加有关。与PER3相关的易感性尚未与腺瘤性息肉一起进行研究。这项探索性病例对照研究首次检验了以下假设：5重复PER3 VNTR序列与腺瘤形成几率增加有关。在结肠镜检查前收集了人口统计学、病史、职业和生活方式等信息。病例组（n = 49）为至少有一个经组织病理学确诊腺瘤的个体。对照组（n = 97）包括检查结果正常或有增生性息肉但无需加强监测的患者。在调整潜在混杂因素后，采用无条件多元逻辑回归计算比值比（OR）及95%置信区间（CI）。34%的参与者检测到腺瘤。与对照组相比，病例组更有可能拥有5重复PER3基因型（4/5 OR，2.1；95% CI，0.9 - 4.8；5/5 OR，5.1；95% CI，1.4 - 18.1；4/5 + 5/5 OR，2.5；95% CI，1.7 - 5.4）。对Oncomine微阵列数据库的检查表明，腺瘤中周期蛋白基因的表达低于相邻正常组织。结果表明需要在更大样本中进行随访。
