食物与营养失调杂志

营养与癌症的视角

阿曼迪奥·维埃拉

营养与癌症研究通常涉及在癌症预防背景下的饮食因素研究，或通过改变饮食来缓和传统癌症治疗的影响。癌症涉及遗传和表观遗传变化，这些变化影响控制细胞生长、死亡和分化的基因表达程序。导致基因组不稳定性的某些变化可能受到饮食和其他环境因素的影响。在这种情况下，基因保护性饮食可被视为有害饮食因素较少、保护性饮食因素充足的饮食。有害因素（例如致癌物）会促进癌症。可能的有益因素包括一些维生素、矿物质和植物化学物质。B 族维生素叶酸是一种可能的保护因素；除其他功能外，它还参与 dTMP（DNA）生物合成并在表观遗传控制中发挥作用，例如 [1-4]。

营养在癌症病因学中的作用很复杂，尚未得到充分理解；一些相关研究很难解释。这种复杂性源于这些研究的不同方面：（a）癌症是一组复杂的疾病；每一种癌症通常都涉及一个慢性、多步骤的病理过程，其特征
是细胞生长和死亡失调、分化丧失、炎症等。（b）人类饮食通常也很复杂；很难分离出特定饮食因素的作用——这些因素通常存在于大多数饮食中——这些因素可以促进或预防致癌的病理过程。（c）另一类问题在于
将实验室研究和动物模型研究应用于致癌作用和人类癌症预防。分离的化合物通常在相对较高的浓度下进行测试，即在食物环境之外。此外，模型生物对饮食化合物的反应和处理方式与人类新陈代谢可能存在重要差异。

At a basic level, cancer development and progression typically involves one or more of the following factors: (i) damage to DNA (mutations). Reactive chemical species such as ROS can cause oxidative damage to DNA, e.g. [5,6]; and this may be exacerbated by deficiency of antioxidants. Other genetic damage may be caused
by deficiencies in nutrients such as folate (see above) or in the cells’ genetic repair systems. (ii) High-level expression of cancerpromoting genes (oncogenes) or reduced expression of protective, tumour-suppressor genes. Such expression may be modified by various dietary factors, e.g. retinoids (from vitamin A) and calciferols (vitamin D). (iii) Suppressed immunity may also contribute to the progression of cancers, and many nutrient deficiencies (e.g. zinc and vitamin A) can compromise immunity.
As an example of gene-diet interactions, one can consider genetically-determined DNA repair efficiency interacting with two general classes of dietary parameters: insufficient intake of a protective factor such as folate or vitamin E, and excessive intake of harmful factors in food such as heterocyclic aromatic amines and other possible carcinogens (Figure 1). An individual with efficient repair systems is likely able to better tolerate potentially damaging nutrient deficiencies, or a relatively higher level of carcinogen exposure. It has been estimated that a majority of adulthood cancers may be caused by environmental factors [7]. (Some early-onset or childhood cancers are likely much less influenced by harmful environmental factors.) There are both dietary (nutrient deficiencies and food carcinogens) and non-dietary (e.g. smoking and radiation) components to such environmental factors. At a global level, major causes of cancer include smoking, UV radiation, obesity, alcohol, infections. Putative dietary carcinogens typically rank lower (except alcohol), but their exact contribution is not well known. Possible food carcinogens may arise from (i) industrial chemicals used to treat foods, e.g., pesticides, (ii) environmental contaminants from air, soil, etc., (iii) food processing, e.g. colours, flavours, and other additives
and (iv) high temperature cooking and exposure to combustion products during cooking. Red meats, rich in heme, have been associated with increased risk of colorectal cancer [8].

血红素铁可参与导致氧化损伤的反应 [9]。高脂肪和高能量饮食会增加某些类型癌症的风险，例如 [10,11]。有趣的是，最近一项涉及高脂肪饮食的动物模型研究表明，手术去除一些脂肪沉积物可以减少紫外线诱发的皮肤癌的发展 [12]。其他研究表明，减肥手术对某些人有益，可降低癌症发病率或进展，例如 [13]。在保护因素方面，根据大量人群水平的研究，水果、蔬菜、茶通常是推荐的。植物性食物有许多潜在的有益因素：
膳食纤维、维生素和其他光化学物质，以及相对较低的热量密度。许多植物化学物质在体外表现出抗氧化活性，但其中许多活性在体内（体内）的潜在相关性尚未得到充分证实。光化学物质可以影响许多细胞功能，从而