Meat intake and bladder cancer in a prospective study: a role for heterocyclic aromatic amines?
Meat intake and bladder cancer in a prospective study: a role for heterocyclic aromatic amines?
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DOI：
10.1007/s10552-008-9121-1
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发表时间：
2008-08-01
影响因子：
2.3
通讯作者：
Vineis, P.
中科院分区：
文献类型：
--
作者：
Lumbreras, B.;Garte, S.;Vineis, P.
目的在熟肉中发现的可疑致癌物质杂环胺(HAAs)在诱发DNA突变之前需要宿主介导的代谢激活。SULT1A1和NAT2在HAA激活中的作用表明，NAT2快速乙酰化基因和SULT1A1等位基因变异可能对HAA的致癌作用有影响。EPIC是一项前瞻性研究，旨在调查营养和癌症之间的关系。信息是通过关于生活方式变量的非饮食调查问卷和饮食调查问卷收集的。受试者仅限于不吸烟的人。结果227例膀胱癌患者和612例对照1：3匹配。肉类摄入量和Nat2基因与膀胱癌风险无独立关联。膀胱癌风险与进食肉类的关系仅在快速的Nat2基因携带者中观察到(OR值为2.9，95%CI为1.0~7.9；OR值为2.9，95%CI为1.0~7.9；OR值为3.6，95%CI为1.3~9.7；OR值为3.6，95%CI为1.3~9.7；OR为3.5，95%CI为1.2~9.7)，而在慢速基因携带者中则不存在。在Logistic回归分析中，NAT2与肉类摄入量之间存在交互作用(P=0.034)。未观察到SULT1A1*1/2和SULT1A1*2/2的相关性。结论肉类摄入量和NAT2与膀胱癌的发病风险有关。他们支持这一假设，即在具有快速NA2乙酰化基因的受试者中，较高水平的HAAs暴露是膀胱癌的危险因素。我们没有观察到SULT1A1等位基因变异对这种癌症的影响。目前的研究增加了关于高肉类摄入量饮食可能产生的长期不良影响的新信息。
Objective 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.Methods 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.Results 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).Conclusions 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.