Red meat intake, NAT2, and risk of colorectal cancer: a pooled analysis of 11 studies.
Red meat intake, NAT2, and risk of colorectal cancer: a pooled analysis of 11 studies.
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DOI：
10.1158/1055-9965.epi-14-0897
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发表时间：
2015-01
期刊：
影响因子：
--
通讯作者：
Chan AT
中科院分区：
文献类型：
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作者：
Ananthakrishnan AN;Du M;Berndt SI;Brenner H;Caan BJ;Casey G;Chang-Claude J;Duggan D;Fuchs CS;Gallinger S;Giovannucci EL;Harrison TA;Hayes RB;Hoffmeister M;Hopper JL;Hou L;Hsu L;Jenkins MA;Kraft P;Ma J;Nan H;Newcomb PA;Ogino S;Potter JD;Seminara D;Slattery ML;Thornquist M;White E;Wu K;Peters U;Chan AT
红肉摄入与结直肠癌（CRC）的风险有关，可能通过杂环胺介导。N-乙酰基转移酶2（NAT 2）的代谢效率所需的代谢活化的这些胺的遗传变异的影响。红肉摄入量，NAT 2基因型和CRC之间的相互作用报道不一致。我们使用了来自结肠癌家族登记处（CCFR）和结直肠癌遗传学和流行病学联盟（GECCO）的汇总个体水平数据。每项研究都收集了红肉摄入量。我们基于rs 1495741的多态性推断NAT 2表型，该多态性高度预测酶活性。在多变量校正模型中使用乘性相互作用项评估相互作用。在11项研究中，纳入了8，290例CRC病例和9，115例对照。与最低四分位数相比，红肉摄入量的最高四分位数与CRC风险增加相关（OR 1.41，95%CI 1.29 - 1.55）。然而，仅在回顾性饮食数据的研究中观察到显著相关性，而在癌症诊断前前瞻性评估饮食的研究中没有观察到显著相关性。结合所有研究，高红肉摄入量与快速/中间NAT 2基因型（OR 1.38，95%CI 1.20 - 1.59）和慢速基因型（OR 1.43，95%CI 1.28 - 1.61）的CRC相关性相似（p-相互作用=0.9）。我们发现，高红肉摄入量与CRC风险增加相关，仅来自回顾性病例对照研究，而不受NAT 2酶活性的影响。我们的研究结果表明NAT 2基因型和红肉摄入量在介导CRC风险方面没有相互作用。
Red meat intake has been associated with risk of colorectal cancer (CRC), potentially mediated through heterocyclic amines. The metabolic efficiency of N-acetyltransferase 2 (NAT2) required for the metabolic activation of such amines is influenced by genetic variation. The interaction between red meat intake, NAT2 genotype, and CRC has been inconsistently reported. We used pooled individual-level data from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Red meat intake was collected by each study. We inferred NAT2 phenotype based on polymorphism at rs1495741, highly predictive of enzyme activity. Interaction was assessed using multiplicative interaction terms in multivariate-adjusted models. From 11 studies, 8,290 CRC cases and 9,115 controls were included. The highest quartile of red meat intake was associated with increased risk of CRC compared to the lowest quartile (OR 1.41, 95%CI 1.29 – 1.55). However, a significant association was observed only for studies with retrospective diet data, not for studies with diet prospectively assessed before cancer diagnosis. Combining all studies, high red meat intake was similarly associated with CRC in those with a rapid/intermediate NAT2 genotype (OR 1.38, 95%CI 1.20 – 1.59) as with a slow genotype (OR 1.43, 95%CI 1.28 – 1.61) (p- interaction=0.9). We found that high red meat intake was associated with increased risk of CRC only from retrospective case-control studies and not modified by NAT2 enzyme activity. Our results suggest no interaction between NAT2 genotype and red-meat intake in mediating risk of CRC.