Lumbreras B, Garte S, Overvad K, Tjonneland A, Clavel-Chapelon F, Linseisen J P, Boeing H, Trichopoulou A, Palli D, Peluso M, Krogh V, Tumino R, Panico S, Bueno-De-Mesquita H B, Peeters P H, Lund E, Martinez C, Dorronsoro M, Barricarte A, Chirlaque M-D, Quiros J R, Berglund G, Hallmans G, Day N E, Key T J, Saracci R, Kaaks R, Malaveille C, Ferrari P, Boffetta P, Norat T, Riboli E, Gonzalez C A, Vineis P
Imperial College London, London, UK .
Cancer Causes Control. 2008 Aug;19(6):649-56. doi: 10.1007/s10552-008-9121-1. Epub 2008 Feb 9.
The suspect carcinogens, heterocyclic amines (HAAs), found in well-done meat require host-mediated metabolic activation before inducing DNA mutations. The role of SULT1A1 and of NAT2 on the activation of HAAs suggests that NAT2 rapid acetylator genotype and SULT1A1 allele variants can have an effect on HAA carcinogenicity.
Data were collected as part of a case-control study nested within the EPIC cohort, the Gen Air investigation. EPIC is a prospective study designed to investigate the relationship between nutrition and cancer. Information was collected through a non-dietary questionnaire on lifestyle variables and through a dietary questionnaire. The subjects were restricted to non-smokers. We calculated the matched odds ratio for bladder cancer risk using logistic regression, controlling for potential confounders.
There were 227 bladder cases and 612 controls matched 1:3. Meat intake and NAT2 genotype were not independently associated with bladder cancer risk. A significant relationship was observed between bladder cancer risk and consumption of meat only among subjects with the rapid NAT2 genotype (odds ratios [OR] 2.9, 95% CI 1.0-7.9 for the 2nd quartile of meat intake; 3.6, 95% CI 1.3-9.7 for the 3rd quartile; and 3.5, 95% CI 1.2-9.7 for the 4th quartile), and was not present among subjects with the slow genotype. An interaction between NAT2 and meat intake was found in logistic regression (P = 0.034). No association was observed for SULT1A *1/2 genotype (1.0; 95% CI 0.7-1.5) and for SULT1A1 *2/2 genotype (0.9; 95% CI 0.5-1.7).
These results are suggestive of a role of meat intake and NAT2 on bladder cancer risk. They support the hypothesis that among subjects with the rapid NAT2 acetylation genotype higher levels of HAAs exposure are a bladder cancer risk factor. We did not observe an effect of SULT1A1 allele variants on this cancer. The present study adds new information on the possible long-term adverse effects of diets with high meat intake.
在熟透的肉类中发现的可疑致癌物杂环胺（HAAs），在诱导DNA突变之前需要宿主介导的代谢激活。SULT1A1和NAT2在HAAs激活中的作用表明，NAT2快速乙酰化基因型和SULT1A1等位基因变体可能会影响HAA的致癌性。
作为EPIC队列（Gen Air调查）中一项巢式病例对照研究的一部分收集数据。EPIC是一项旨在研究营养与癌症之间关系的前瞻性研究。通过一份关于生活方式变量的非饮食问卷和一份饮食问卷收集信息。研究对象仅限于不吸烟者。我们使用逻辑回归计算膀胱癌风险的匹配比值比，并对潜在的混杂因素进行控制。
共有227例膀胱癌病例和612例对照，病例与对照按1:3匹配。肉类摄入量和NAT2基因型与膀胱癌风险无独立关联。仅在NAT2快速基因型的受试者中观察到膀胱癌风险与肉类消费之间存在显著关系（肉类摄入量第二四分位数的比值比[OR]为2.9，95%可信区间为1.0 - 7.9；第三四分位数为3.6，95%可信区间为1.3 - 9.7；第四四分位数为3.5，95%可信区间为1.2 - 9.7），而在慢基因型受试者中未观察到这种关系。在逻辑回归中发现NAT2与肉类摄入量之间存在交互作用（P = 0.034）。未观察到SULT1A *1/2基因型（1.0；95%可信区间为0.7 - 1.5）和SULT1A1 *2/2基因型（0.9；95%可信区间为0.5 - 1.7）与膀胱癌风险有关联。
这些结果提示肉类摄入量和NAT2在膀胱癌风险中起作用。它们支持这样的假设，即在NAT2乙酰化快速基因型的受试者中，较高水平的HAA暴露是膀胱癌的一个风险因素。我们未观察到SULT1A1等位基因变体对这种癌症有影响。本研究为高肉类摄入量饮食可能产生的长期不良影响增添了新信息。
