Department of Food and Nutrition, Sookmyung Women's University.
Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang.
Eur J Cancer Prev. 2019 Jul;28(4):304-310. doi: 10.1097/CEJ.0000000000000462.
The association between red meat intake and colorectal cancer (CRC) may be modulated by genetic polymorphisms of cytochrome P450 2E1 (CYP2E1), a key enzyme in the metabolism of nitrosamines, and peroxisome proliferator-activated receptor gamma (PPARγ), a transcription factor involved in adipogenesis and lipid and glucose metabolism. We conducted a case-control study of 971 patients with CRC and 658 controls who were admitted to two university hospitals between 1995 and 2004 in Seoul, Korea. Participants were asked about red meat intake by using a validated food frequency questionnaire. Polymorphisms of CYP2E1 (rs3813867) and PPARγ (rs1801282 or rs3856806) were identified using the TaqMan assay. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable logistic regression models. We found that the association between red meat and CRC varied by CYP2E1 polymorphisms; ORs (95% CIs) for at least five or more vs. less than one time/week of red meat intake were 2.77 (1.23-6.25) among individuals with C alleles of CYP2E1 and 0.89 (0.51-1.54) among individuals with the GG allele (Pinteraction=0.05). Compared with those individuals with the CC allele, increasing risk of CRC with increasing red meat intake was more pronounced among individuals with T alleles of PPARγC161T (rs3856806), but the association was not significant. Our data provide evidence that East Asians with the variant type of CYP2E1 may have high susceptibility to development of CRC risk.
红肉类摄入量与结直肠癌（CRC）之间的关联可能受到细胞色素 P450 2E1（CYP2E1）和过氧化物酶体增殖物激活受体γ（PPARγ）基因多态性的调节，CYP2E1 是亚硝胺代谢的关键酶，而 PPARγ 是参与脂肪生成以及脂质和葡萄糖代谢的转录因子。我们对 1995 年至 2004 年间在韩国首尔的两家大学医院就诊的 971 例 CRC 患者和 658 例对照进行了病例对照研究。通过验证过的食物频率问卷，询问参与者的红肉类摄入量。使用 TaqMan 测定法确定 CYP2E1（rs3813867）和 PPARγ（rs1801282 或 rs3856806）的多态性。我们使用多变量逻辑回归模型计算了比值比（OR）和 95％置信区间（CI）。我们发现，CYP2E1 多态性与红肉类和 CRC 之间的关联不同；CYP2E1 等位基因 C 携带者中至少每周摄入五次或更多次红肉类与少于一次的摄入相比，OR（95％CI）为 2.77（1.23-6.25），而 GG 等位基因携带者的 OR 为 0.89（0.51-1.54）（P 交互=0.05）。与 CC 等位基因携带者相比，在 PPARγC161T（rs3856806）中携带 T 等位基因的个体中，随着红肉类摄入量的增加，CRC 的风险增加更为明显，但关联没有统计学意义。我们的数据提供了证据，表明东亚人携带变异型 CYP2E1 可能对 CRC 风险的发展具有较高的易感性。
