Alabaster O, Tang Z, Shivapurkar N
Institute for Disease Prevention, George Washington University Medical Center, Washington DC, USA.
Mutat Res. 1996 Feb 19;350(1):185-97. doi: 10.1016/0027-5107(95)00114-x.
Comparative international epidemiological data indicate that the difference between the highest and lowest colon cancer incidence is approximately 10-fold. This suggests that the dominant causes of colon cancer are environmental rather than genetic in origin, with the dominant environmental cause being the typical diet of Western industrialized countries. Many epidemiological and experimental studies have suggested an important role for dietary fiber in the prevention of colon cancer. Using the Fischer-344 rat as the experimental model, data clearly demonstrate a strong protective effect of a diet that is low in fat, high in fiber and high in calcium (low-risk diet). Such a diet prevents the development of both preneoplastic aberrant crypt foci (ACF) and colon tumors. Recent experiments have also demonstrated a direct relationship between a ras point mutation in ACF at different stages of rat colon carcinogenesis, and a ras point mutation that is subsequently present in colon tumors. Using wheat bran as the model dietary fiber source, its effects were compared to the effects of psyllium, phytic acid, vitamin E, beta-carotene, folic acid, alone or in combination, for their ability to prevent colon cancer in rats on high-risk Western-style diets. Our studies clearly demonstrated the ability of wheat bran to reduce ACF and colon tumors in rats that consumed high-fat, Western-style diets. Although phytic acid, which is a constituent of wheat bran, alone demonstrated strong cancer-preventive potential, our experiments provided evidence for the cancer-preventive effect of the crude fiber fraction that is independent of the effect of phytic acid. The synergistic combination of wheat bran with the soluble fiber psyllium led to enhanced protection; while the combination of wheat bran with beta-carotene showed only an additive effect. Beta-carotene appeared to show higher protection than wheat bran at an intake level that is nutritionally relevant to humans, suggesting the possibility of using beta-carotene to enhance the effects of dietary fiber in high-risk Western populations. Using ACF as an intermediate endpoint, it was also shown that vitamin E and beta-carotene appear to inhibit progression of ACF to colon cancer, while wheat bran and folic acid appeared to have weak cancer-preventive potential at this late stage of carcinogenesis. In conclusion, wheat bran alone, or in combination with psyllium, appears to have greater potential to inhibit earlier phases of carcinogenesis, while beta-carotene and vitamin E may also inhibit later stages of carcinogenesis. Despite considerable epidemiological and experimental evidence that increasing the fiber and lowering the fat content of the Western diet could substantially reduce the risk of cancer and heart disease, the real challenge is to find effective ways to educate and motivate people to overcome their intrinsic cultural resistance to such changes in their eating habits.
国际比较流行病学数据表明，结肠癌发病率最高与最低之间的差异约为10倍。这表明结肠癌的主要病因是环境因素而非遗传因素，主要环境病因是西方工业化国家的典型饮食。许多流行病学和实验研究表明膳食纤维在预防结肠癌中具有重要作用。以Fischer-344大鼠作为实验模型，数据清楚地证明了低脂肪、高纤维和高钙饮食（低风险饮食）具有强大的保护作用。这种饮食可预防癌前异常隐窝灶（ACF）和结肠肿瘤的发生。最近的实验还证明了大鼠结肠癌发生不同阶段ACF中的ras点突变与随后结肠肿瘤中出现的ras点突变之间存在直接关系。以麦麸作为膳食纤维来源模型，将其与车前子、植酸、维生素E、β-胡萝卜素、叶酸单独或联合使用的效果进行比较，观察它们对食用高风险西式饮食大鼠预防结肠癌的能力。我们的研究清楚地证明了麦麸能够减少食用高脂肪西式饮食大鼠的ACF和结肠肿瘤。虽然麦麸的成分之一植酸单独显示出强大的防癌潜力，但我们的实验提供了证据，证明粗纤维部分具有独立于植酸作用的防癌效果。麦麸与可溶性纤维车前子的协同组合增强了保护作用；而麦麸与β-胡萝卜素的组合仅显示出相加作用。在与人类营养相关的摄入量水平上，β-胡萝卜素似乎比麦麸显示出更高的保护作用，这表明有可能使用β-胡萝卜素增强高风险西方人群中膳食纤维的效果。以ACF作为中间终点，还表明维生素E和β-胡萝卜素似乎抑制ACF向结肠癌的进展，而麦麸和叶酸在致癌作用的这个后期阶段似乎具有较弱的防癌潜力。总之，单独的麦麸或与车前子联合使用，似乎在抑制致癌作用早期阶段具有更大潜力，而β-胡萝卜素和维生素E也可能抑制致癌作用后期阶段。尽管有大量流行病学和实验证据表明，增加西方饮食中的纤维含量并降低脂肪含量可大幅降低患癌症和心脏病的风险，但真正的挑战是找到有效的方法来教育和激励人们克服他们对饮食习惯这种改变的内在文化抵触情绪。
