Combined influence of genetic and dietary factors on colorectal cancer incidence in Japanese Americans.
Combined influence of genetic and dietary factors on colorectal cancer incidence in Japanese Americans.
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DOI：
10.1093/oxfordjournals.jncimonographs.a024220
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发表时间：
1999-12
期刊：
影响因子：
--
通讯作者：
L. Marchand
中科院分区：
文献类型：
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作者：
L. Marchand
日本移民到美国的结直肠癌(CRC)发病率迅速上升，超过了东道国人口的水平。夏威夷和加利福尼亚州的日本人的CRC比率现在是世界上最高的。在日本，这种疾病的发病率也有所上升，这可能是饮食西化的结果。在夏威夷进行了一系列以人群为基础的研究，以确定哪些饮食因素导致日本人对结直肠癌的显著易感性，以及是否也涉及遗传因素。第一项病例对照研究表明，在夏威夷的日本男性中，大量摄入红肉是疾病的主要危险因素，一级亲属的结直肠癌家族史可能强烈改变这种联系。目前正在完成一项病例对照家庭研究，以进一步探讨在对家庭成员的环境变量进行调整后，家族史与红肉摄入量之间的相互作用。此外，隔离分析将指导在结直肠癌研究合作家庭登记中招募的高危日本家庭中的基因发现研究。回顾和前瞻性研究也在进行中，以测试结直肠癌与控制与高红肉饮食相关的致癌物的代谢激活或解毒的基因的特定多态性的相关性。初步结果表明，在食用熟制红肉的个体中，快速NAT2基因型和快速CYP1A2表型与结直肠癌相关。癌症发病率发生戏剧性变化的人群可能提供识别基因-环境相互作用的机会。
Colorectal cancer (CRC) rates for Japanese migrants to the United States increased rapidly to surpass the level of the host population. CRC rates for the Japanese in Hawaii and California are now the highest in the world. Rates for this disease have also increased in Japan, presumably as the result of the westernization of the diet. A series of population-based studies in Hawaii was undertaken to determine which dietary factors are responsible for this remarkable susceptibility of the Japanese to CRC and whether genetic factors are also involved. A first case-control study suggested that a high intake of red meat is a major risk factor for the disease in Hawaii Japanese men and that family history of CRC among first-degree relatives may strongly modify this association. A case-control family study is currently being completed to explore further the interaction between family history and the intake of red meat after adjustment for environmental covariates among family members. Also, a segregation analysis will guide gene discovery studies among high-risk Japanese families being recruited in the Cooperative Family Registry for Colorectal Cancer Studies. Retrospective and prospective studies are also ongoing to test associations of CRC with specific polymorphisms in genes controlling the metabolic activation or detoxification of the carcinogens associated with a diet high in red meat. Preliminary results suggest an association of the combined rapid NAT2 genotype and rapid CYP1A2 phenotype with CRC in individuals consuming well-done red meat. Populations in which dramatic changes in cancer incidence have occurred may offer opportunities to identify gene-environment interactions.