Department of Epidemiology, Public Health College, Harbin Medical University, 157, Baojian Street, Nangang District, Harbin, Heilongjiang Province, People's Republic of China.
Med Oncol. 2013;30(3):565. doi: 10.1007/s12032-013-0565-0. Epub 2013 May 29.
Caspase (CASP) 3, 8, 9 are important caspases in the apoptosis pathway and play important roles in development and progression of cancer. A case-control study with 451 colorectal cancer (CRC) patients and 631 cancer-free controls were carried out, and CRC patients followed up, to investigate the associations between three main polymorphisms and colorectal cancer risk and prognosis, and their potential interactions with environmental factors on CRC risk among Chinese people. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism and polymerase chain reaction-single strand conformation polymorphism sequencing. Odds ratio (OR), hazard ratio (HR) and their 95 % confidence intervals (CIs) were estimated with unconditional logistic-regression and Cox proportion hazard model. Individuals harboring the CASP8 -652 6N ins/del plus del/del genotype had a slightly lower risk for CRC compared those with ins/ins genotype (adjusted OR = 0.77, 95 % CI 0.59-0.99, P = 0.04). Significant associations between CASP3 -928 GG genotype and CASP9 -1263 GG genotype and reduced risk of rectal cancer were observed (adjusted OR = 0.56, 95 % CI 0.34-0.92, P = 0.02; adjusted OR = 0.59, 95 % CI 0.36-0.95, P = 0.03, respectively). There was a marginal significant association between CASP8 -652 6N ins/del polymorphism and CRC prognosis (ins/del versus ins/ins, adjusted HR = 0.69, 95 % CI 0.48-0.99, P = 0.04). These findings suggested these polymorphisms and their combinations with dietary factors may be associated with the development of CRC. CASP8 -652 6N ins/del polymorphism may be an independent survival predictor for CRC.
Caspase (CASP) 3, 8, 9 是细胞凋亡途径中的重要半胱氨酸蛋白酶，在癌症的发生和发展中发挥重要作用。本研究通过病例对照研究，纳入 451 例结直肠癌（CRC）患者和 631 例无癌对照，并对 CRC 患者进行随访，探讨了三种主要多态性与结直肠癌风险和预后的关系，以及它们与环境因素在中国人 CRC 风险中的潜在相互作用。通过聚合酶链反应-限制性片段长度多态性和聚合酶链反应-单链构象多态性测序确定基因型。使用非条件逻辑回归和 Cox 比例风险模型估计比值比（OR）、风险比（HR）及其 95%置信区间（CI）。与 ins/ins 基因型相比，携带 CASP8-652 6N ins/del 加 del/del 基因型的个体 CRC 风险略低（调整 OR=0.77，95%CI 0.59-0.99，P=0.04）。还观察到 CASP3-928 GG 基因型和 CASP9-1263 GG 基因型与直肠癌风险降低之间存在显著关联（调整 OR=0.56，95%CI 0.34-0.92，P=0.02；调整 OR=0.59，95%CI 0.36-0.95，P=0.03）。CASP8-652 6N ins/del 多态性与 CRC 预后之间存在边缘显著关联（ins/del 与 ins/ins，调整 HR=0.69，95%CI 0.48-0.99，P=0.04）。这些发现表明，这些多态性及其与饮食因素的组合可能与 CRC 的发生有关。CASP8-652 6N ins/del 多态性可能是 CRC 独立的生存预测因子。
