Dashwood R H
The Linus Pauling Institute, Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331-6512, USA.
Oncol Rep. 1999 Mar-Apr;6(2):277-81.
Colorectal cancer is a leading cause of cancer-related deaths, and the two most important considerations for avoidance of this disease are early detection and prevention. If metastasis has occurred to distant sites, such as the liver and lung, the 5-year survival rate for colorectal cancer is below 10%, but this increases to greater than 90% when the cancer is found early. Early detection can be facilitated by use of the digital rectal exam, fecal occult blood test, sigmoidoscopy, and colonoscopy, but these methods might be supplemented in the future by other screening assays using intermediate biomarkers. One interesting biomarker, the aberrant crypt focus (ACF), has been observed in resected human colons, and is the earliest detectable morphological change in the colons of experimental animals treated with carcinogens such as the cooked meat heterocyclic amines. The ACF can also be used as an end-point to screen for potential inhibitors of colorectal cancer; using this approach, we identified conjugated linoleic acids, indole-3-carbinol, chlorophyllin, and tea polyphenols as promising inhibitors in the colon. These compounds can be added to a growing list of natural and synthetic agents that might be effective against colorectal cancer, including selenium, calcium, and nonsteroidal anti-inflammatory agents. However, results from human clinical trials with several of these compounds have highlighted the need for detailed mechanism data before recommendations can be made for wide-scale use in humans. In the meantime, the best approach to reducing the risk of colorectal cancer would be to increase the dietary intake of fruits, vegetables and cereals, while reducing the overall intake of fat, particularly from animal sources.
结直肠癌是癌症相关死亡的主要原因之一,预防这种疾病的两个最重要的考虑因素是早期检测和预防。如果已经发生远处转移,如转移至肝脏和肺部,结直肠癌的5年生存率低于10%,但如果癌症早期发现,这一比例可升至90%以上。数字直肠检查、粪便潜血试验、乙状结肠镜检查和结肠镜检查有助于早期检测,但未来可能会通过使用中间生物标志物的其他筛查检测方法进行补充。一种有趣的生物标志物——异常隐窝灶(ACF),已在切除的人体结肠中观察到,并且是在用致癌物如熟肉杂环胺处理的实验动物结肠中最早可检测到的形态学变化。ACF还可作为筛选结直肠癌潜在抑制剂的终点;使用这种方法,我们确定共轭亚油酸、吲哚 - 3 - 甲醇、叶绿酸和茶多酚是结肠中有前景的抑制剂。这些化合物可以添加到可能有效对抗结直肠癌的天然和合成药物的不断增加的列表中,包括硒、钙和非甾体抗炎药。然而,对其中几种化合物进行的人体临床试验结果强调,在建议大规模用于人类之前,需要详细的作用机制数据。与此同时,降低结直肠癌风险的最佳方法是增加水果、蔬菜和谷物的饮食摄入量,同时减少总体脂肪摄入量,特别是来自动物来源的脂肪。