Department of Epidemiology, Public Health College, Harbin Medical University, 157, Baojian Street, Nangang District, Harbin, Heilongjiang Province, People's Republic of China.
Fam Cancer. 2013 Dec;12(4):755-65. doi: 10.1007/s10689-013-9659-2.
Cyclooxygenase-2 (COX-2), 12-lipoxygenase (12-LOX) and phospholipaseA2 (PLA2) played important roles in the modulation of apoptosis, angiogenesis, carcinogenesis and invasion of colorectal cancer (CRC). The polymorphisms in COX-2, 12-LOX and PLA2 may affect their roles. Therefore, we investigated if COX-2 -1195G > A, 12-LOX 261Arg > Gln and PLA2 c.349 + 191A > G polymorphisms were associated with risk and prognosis of CRC as well as possible interactions with the environmental factors on the risk of CRC in Northeast of China. A case-control study with 451 cases and 631 controls were carried out, a cohort with 386 patients were followed up. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Compared with the 261Arg/Arg genotype, 12-LOX 261Arg/Gln genotype and 261Arg/Gln + Gln/Gln genotypes reduced the risk of rectal cancer by 33% (adjusted OR = 0.67, 95% CI 0.47-0.97, p = 0.03) and 32% (adjusted OR = 0.68, 95% CI 0.49-0.96, p = 0.03), respectively. The adjusted HR for the association between 12-LOX 261Gln/Gln genotype and overall survival in patients with CRC was 1.68 (95% CI 1.06-2.68, p = 0.03). There was also evidence of an interaction between the PLA2 c.349 + 191 A > G genotypes and the overnight food consumption (adjusted ORi = 1.92, 95% CI 1.14-3.25, P(interaction) = 0.01). These observations indicate that 12-LOX 261Arg > Gln polymorphism may affect risk of rectal cancer, and it may be a potential predictive marker for prognosis of CRC.
环氧化酶-2（COX-2）、12-脂氧合酶（12-LOX）和磷脂酶 A2（PLA2）在调节结直肠癌（CRC）的细胞凋亡、血管生成、癌变和侵袭中发挥重要作用。COX-2、12-LOX 和 PLA2 中的多态性可能影响其作用。因此，我们研究了 COX-2-1195G>A、12-LOX 261Arg>Gln 和 PLA2 c.349+191A>G 多态性是否与中国东北地区 CRC 的风险和预后相关，以及与环境因素的可能相互作用对 CRC 的风险的影响。我们进行了一项病例对照研究，纳入了 451 例病例和 631 例对照，对 386 例患者进行了随访。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）确定基因型。与 261Arg/Arg 基因型相比，12-LOX 261Arg/Gln 基因型和 261Arg/Gln+Gln/Gln 基因型使直肠癌的风险分别降低了 33%（调整后的 OR=0.67，95%CI 0.47-0.97，p=0.03）和 32%（调整后的 OR=0.68，95%CI 0.49-0.96，p=0.03）。在 CRC 患者中，12-LOX 261Gln/Gln 基因型与总生存的关联的调整 HR 为 1.68（95%CI 1.06-2.68，p=0.03）。还存在 PLA2 c.349+191A>G 基因型与夜间食物摄入之间的交互作用的证据（调整后的 ORi=1.92，95%CI 1.14-3.25，P（交互）=0.01）。这些观察结果表明，12-LOX 261Arg>Gln 多态性可能影响直肠癌的风险，并且它可能是 CRC 预后的潜在预测标志物。
