Fels Institute for Cancer Research and Molecular Biology and Department of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania 19140; email:
Department of Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania 19140; email:
Annu Rev Nutr. 2016 Jul 17;36:665-81. doi: 10.1146/annurev-nutr-121415-112634. Epub 2016 Mar 23.
The search for a connection between diet and human cancer has a long history in cancer research, as has interest in the mechanisms by which dietary factors might increase or decrease cancer risk. The realization that altering diet can alter the epigenetic state of genes and that these epigenetic alterations might increase or decrease cancer risk is a more modern notion, driven largely by studies in animal models. The connections between diet and epigenetic alterations, on the one hand, and between epigenetic alterations and cancer, on the other, are supported by both observational studies in humans as well as animal models. However, the conclusion that diet is linked directly to epigenetic alterations and that these epigenetic alterations directly increase or decrease the risk of human cancer is much less certain. We suggest that true and measurable effects of diet or dietary supplements on epigenotype and cancer risk are most likely to be observed in longitudinal studies and at the extremes of the intersection of dietary risk factors and human population variability. Careful analysis of such outlier populations is most likely to shed light on the molecular mechanisms by which suspected environmental risk factors drive the process of carcinogenesis.
在癌症研究中,探寻饮食与人类癌症之间的联系由来已久,人们同样关注饮食因素影响癌症风险的机制。人们逐渐意识到,改变饮食可以改变基因的表观遗传状态,而这些表观遗传改变可能会增加或降低癌症风险,这种现代观念主要受到动物模型研究的推动。一方面,饮食与表观遗传改变之间,以及另一方面,表观遗传改变与癌症之间的联系,既得到了人类观察性研究的支持,也得到了动物模型的支持。然而,饮食与表观遗传改变直接相关,这些表观遗传改变直接增加或降低人类癌症风险的结论远不那么确定。我们认为,饮食或膳食补充剂对表型和癌症风险的真正和可测量的影响最有可能在纵向研究和饮食风险因素与人类群体变异性交叉的极端情况下观察到。对这些离群值人群的仔细分析最有可能揭示可疑环境风险因素驱动致癌过程的分子机制。