Giovannucci E
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Adv Exp Med Biol. 1999;472:29-42. doi: 10.1007/978-1-4757-3230-6_3.
A variety of external factors interacting with genetic susceptibility influence the carcinogenesis process. External factors including oxidative compounds, electrophilic agents, and chronic infections may enhance genetic damage. In addition, various hormonal factors which influence growth and differentiation are critically important in the carcinogenic process. Diet and nutrition can influence these processes directly in the gastrointestinal tract by providing bioactive compounds to specific tissues via the circulatory system, or by modulating hormone levels. Differences in certain dietary patterns among populations explain a substantial proportion of cancers of the colon, prostate and breast. These malignancies are largely influenced by a combination of factors related to diet and nutrition. Their causes are multifactorial and complex, but a major influence is the widespread availability of energy-dense, highly processed and refined foods that are also deplete in fiber. These dietary patterns in combination with physical inactivity contribute to obesity and metabolic consequences such as increased levels of IGF-1, insulin, estrogen, and possibly testosterone. These hormones tend to promote cellular growth. For prostate cancer, epidemiologic studies consistently show a positive association with high consumption of milk, dairy products, and meats. These dietary factors tend to decrease 1.25(OH)2 vitamin D, a cell differentiator, and low levels of this hormone may enhance prostate carcinogenesis. While the nutritional modulation of growth-enhancing and differentiating hormones is likely to contribute to the high prevalence of breast, colorectal, prostate, and several other cancers in the Western world, these cancers are relatively rare in less economically developed countries, where malignancies of the upper gastrointestinal tract are quite common. The major causes of upper gastrointestinal tract cancers are likely related to various food practices or preservation methods other than refrigeration, which increase mucosal exposure to irritants or carcinogens.
多种外部因素与遗传易感性相互作用，影响着癌症发生过程。包括氧化化合物、亲电试剂和慢性感染在内的外部因素可能会加剧基因损伤。此外，各种影响生长和分化的激素因素在致癌过程中至关重要。饮食和营养可通过循环系统向特定组织提供生物活性化合物，或通过调节激素水平，直接在胃肠道影响这些过程。不同人群的某些饮食模式差异可解释相当一部分结肠癌、前列腺癌和乳腺癌的发生。这些恶性肿瘤在很大程度上受与饮食和营养相关的多种因素综合影响。其病因是多因素且复杂的，但一个主要影响因素是能量密集、高度加工和精制且纤维含量低的食物广泛可得。这些饮食模式与缺乏身体活动共同导致肥胖和代谢后果，如胰岛素样生长因子-1、胰岛素、雌激素以及可能的睾酮水平升高。这些激素往往会促进细胞生长。对于前列腺癌，流行病学研究一致表明，大量食用牛奶、乳制品和肉类与之呈正相关。这些饮食因素往往会降低作为细胞分化剂的1,25(OH)₂维生素D水平，而这种激素水平低可能会增强前列腺癌的发生。虽然对促进生长和分化的激素进行营养调节可能是西方世界乳腺癌、结直肠癌、前列腺癌和其他几种癌症高发的原因之一，但在经济欠发达国家，这些癌症相对罕见，而上消化道恶性肿瘤在这些国家相当常见。上消化道癌症的主要原因可能与除冷藏以外的各种食物处理方式或保存方法有关，这些方式会增加黏膜接触刺激物或致癌物的机会。
