Department of Epidemiology and Health Statistics, School of Medicine, Zhejiang University, Hangzhou 310058, China.
J Zhejiang Univ Sci B. 2013 Jan;14(1):47-57. doi: 10.1631/jzus.B1200218.
The initiators caspase-9 (CASP9) and caspase-10 (CASP10) are two key controllers of apoptosis and play important roles in carcinogenesis. This study aims to explore the association between CASPs gene polymorphisms and colorectal cancer (CRC) susceptibility in a population-based study. A two-stage designed population-based case-control study was carried out, including a testing set with 300 cases and 296 controls and a validation set with 206 cases and 845 controls. A total of eight tag selected single nucleotide polymorphisms (SNPs) in CASP9 and CASP10 were chosen based on HapMap and the National Center of Biotechnology Information (NCBI) datasets and genotyped by restriction fragment length polymorphism (RFLP) assay. Multivariate logistic regression models were applied to evaluate the association of SNPs with CRC risk. In the first stage, from eight tag SNPs, three polymorphisms rs4646077 (odds ratio (OR)(AA+AG): 0.654, 95% confidence interval (CI): 0.406-1.055; P=0.082), rs4233532 (OR(CC): 1.667, 95% CI: 0.967-2.876; OR(CT): 1.435, 95% CI: 0.998-2.063; P=0.077), and rs2881930 (OR(CC): 0.263, 95% CI: 0.095-0.728, P=0.036) showed possible association with CRC risk. However, none of the three SNPs, rs4646077 (OR(AA+AG): 1.233, 95% CI: 0.903-1.683), rs4233532 (OR(CC): 0.892, 95% CI: 0.640-1.243; OR(CT): 1.134, 95% CI: 0.897-1.433), and rs2881930 (OR(CC): 1.096, 95% CI: 0.620-1.938; OR(CT): 1.009, 95% CI: 0.801-1.271), remained significant with CRC risk in the validation set, even after stratification for different tumor locations (colon or rectum). In addition, never tea drinking was associated with a significantly increased risk of CRC in testing set together with validation set (OR: 1.755, 95% CI: 1.319-2.334). Our results found that polymorphisms of CASP9 and CASP10 genes may not contribute to CRC risk in Chinese population and thereby the large-scale case-control studies might be in consideration. In addition, tea drinking was a protective factor for CRC.
启动子 caspase-9（CASP9）和 caspase-10（CASP10）是细胞凋亡的两个关键控制器，在肿瘤发生中发挥着重要作用。本研究旨在探讨 CASPs 基因多态性与人群中结直肠癌（CRC）易感性的关系。本研究采用基于人群的两阶段设计病例对照研究，包括 300 例病例和 296 例对照的检测集，以及 206 例病例和 845 例对照的验证集。基于 HapMap 和国家生物技术信息中心（NCBI）数据集，选择了 CASP9 和 CASP10 中的 8 个标签选择单核苷酸多态性（SNP），并通过限制性片段长度多态性（RFLP）分析进行基因分型。采用多变量逻辑回归模型评估 SNP 与 CRC 风险的相关性。在第一阶段，从 8 个标签 SNP 中，有 3 个多态性 rs4646077（比值比（OR）（AA+AG）：0.654，95%置信区间（CI）：0.406-1.055；P=0.082）、rs4233532（OR（CC）：1.667，95% CI：0.967-2.876；OR（CT）：1.435，95% CI：0.998-2.063；P=0.077）和 rs2881930（OR（CC）：0.263，95% CI：0.095-0.728，P=0.036）与 CRC 风险可能相关。然而，在验证集中，这三个 SNP（rs4646077（OR（AA+AG）：1.233，95% CI：0.903-1.683）、rs4233532（OR（CC）：0.892，95% CI：0.640-1.243；OR（CT）：1.134，95% CI：0.897-1.433）和 rs2881930（OR（CC）：1.096，95% CI：0.620-1.938；OR（CT）：1.009，95% CI：0.801-1.271）与 CRC 风险均无统计学意义，即使对不同肿瘤部位（结肠或直肠）进行分层后也是如此。此外，从不饮茶与检测集和验证集中 CRC 的风险显著增加相关（OR：1.755，95% CI：1.319-2.334）。我们的研究结果发现，CASP9 和 CASP10 基因的多态性可能不会导致中国人群患 CRC 的风险增加，因此可能需要进行大规模的病例对照研究。此外，饮茶是 CRC 的保护因素。
