Sinha R, Kulldorff M, Chow W H, Denobile J, Rothman N
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Maryland 20892, USA.
Cancer Epidemiol Biomarkers Prev. 2001 May;10(5):559-62.
Meats cooked well-done by high temperature techniques produce mutagenic compounds such as heterocyclic amines (HCAs), but the amounts of these compounds vary by cooking techniques, temperature, time, and type of meat. We investigated the role of HCAs in the etiology of colorectal adenomas and the extent to which they may explain the previously observed risk for red meat and meat-cooking methods. In a case-control study of colorectal adenomas, cases (n = 146) were diagnosed with colorectal adenomas at sigmoidoscopy or colonoscopy, and controls (n = 228) were found not to have colorectal adenomas at sigmoidoscopy. Using a meat-derived HCA and mutagen database and responses from a meat-cooking questionnaire module, we estimated intake of 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and mutagenic activity. We calculated odds ratios and 95% confidence intervals using logistic regression adjusting for several established risk factors for colorectal adenomas or cancer. The odds ratios (95% confidence interval; P for trend test) fifth versus first quintiles are: 2.2 (1.2-4.1; P = 0.02) for DiMeIQx; 2.1 (1.0-4.3; P = 0.002) for MeIQx; 2.5(1.1-5.5; P = 0.02) for PhIP; and 3.1 (1.4-6.8; P = 0.001) for mutagenic activity. When the three HCAs were adjusted for the other two, only the trend for MeIQx (P = 0.04) remained statistically significant. When we tried to disentangle the relative contribution of the three HCAs from the meat variables, we found that MeIQx remained significantly associated with risk even when adjusted for red meat but not vice versa. When MeIQx and well-done meat were analyzed in the same model, the risks were attenuated for both. Mutagenic activity from meat remained significantly associated with increased risk even when adjusted for intake of red meat or well-done red meat, whereas the red meat and well-done red meat associations were no longer significant when adjusted for total mutagenic activity. In conclusion, we found an elevated risk of colorectal adenomas associated with high intake of certain HCAS: Further, mutagenic activity from cooked meat consumption, a measure that integrates all of the classes of mutagens, was strongly associated with risk and explained the excess risk with intake of well-done red meat.
通过高温技术烹制的熟透肉类会产生诱变化合物，如杂环胺（HCAs），但这些化合物的含量会因烹饪技术、温度、时间和肉类种类而有所不同。我们研究了杂环胺在结直肠腺瘤病因学中的作用，以及它们在多大程度上可以解释先前观察到的红肉及肉类烹饪方法与患病风险之间的关系。在一项结直肠腺瘤的病例对照研究中，病例组（n = 146）在乙状结肠镜检查或结肠镜检查中被诊断为结直肠腺瘤，对照组（n = 228）在乙状结肠镜检查中未发现结直肠腺瘤。利用肉类来源的杂环胺和诱变剂数据库以及肉类烹饪问卷模块的回答，我们估算了2-氨基-3,4,8-三甲基咪唑并[4,5-f]喹喔啉（DiMeIQx）、2-氨基-3,8-二甲基咪唑并[4,5-f]喹喔啉（MeIQx）、2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶（PhIP）的摄入量以及诱变活性。我们使用逻辑回归计算比值比和95%置信区间，并对几种已确定的结直肠腺瘤或癌症风险因素进行了调整。第五分位数与第一分位数的比值比（95%置信区间；趋势检验P值）分别为：DiMeIQx为2.2（1.2 - 4.1；P = 0.02）；MeIQx为2.1（1.0 - 4.3；P = 0.002）；PhIP为2.5（1.1 - 5.5；P = 0.02）；诱变活性为3.1（1.4 - 6.8；P = 0.001）。当对三种杂环胺中的一种进行另外两种的调整时，只有MeIQx的趋势（P = 0.04）仍具有统计学意义。当我们试图从肉类变量中区分出三种杂环胺的相对贡献时，我们发现即使在对红肉进行调整后，MeIQx与风险仍显著相关，反之则不然。当在同一模型中分析MeIQx和熟透的肉类时，两者的风险均有所降低。即使在对红肉或熟透的红肉摄入量进行调整后，肉类的诱变活性与风险增加仍显著相关；而在对总诱变活性进行调整后，红肉和熟透的红肉与风险的关联不再显著。总之，我们发现某些杂环胺的高摄入量与结直肠腺瘤风险升高有关；此外，食用熟肉产生的诱变活性（一种整合了所有诱变剂类别的指标）与风险密切相关，并解释了食用熟透红肉带来的额外风险。
