Payne Claire M, Crowley-Skillicorn Cheray, Bernstein Carol, Holubec Hana, Bernstein Harris
Department of Cell Biology and Anatomy, College of Medicine, University of Arizona Tucson, AZ, USA.
Clin Exp Gastroenterol. 2011;4:75-119. doi: 10.2147/CEG.S17114. Epub 2011 May 3.
Chromosomal instability is a major pathway of sporadic colon carcinogenesis. Chromosome arm 1p appears to be one of the "hot spots" in the non-neoplastic mucosa that, when deleted, is associated with the initiation of carcinogenesis. Chromosome arm 1p contains genes associated with DNA repair, spindle checkpoint function, apoptosis, multiple microRNAs, the Wnt signaling pathway, tumor suppression, antioxidant activities, and defense against environmental toxins. Loss of 1p is dangerous since it would likely contribute to genomic instability leading to tumorigenesis. The 1p deletion-associated colon carcinogenesis pathways are reviewed at the molecular and cellular levels. Sporadic colon cancer is strongly linked to a high-fat/low-vegetable/low-micronutrient, Western-style diet. We also consider how selected dietary-related compounds (eg, excess hydrophobic bile acids, and low levels of folic acid, niacin, plant-derived antioxidants, and other modulatory compounds) might affect processes leading to chromosomal deletions, and to the molecular and cellular pathways specifically altered by chromosome 1p loss.
染色体不稳定是散发性结肠癌发生的主要途径。染色体臂1p似乎是非肿瘤性黏膜中的“热点”之一，其缺失与致癌作用的起始相关。染色体臂1p包含与DNA修复、纺锤体检查点功能、细胞凋亡、多种微小RNA、Wnt信号通路、肿瘤抑制、抗氧化活性以及抵御环境毒素相关的基因。1p缺失是危险的，因为它可能导致基因组不稳定从而引发肿瘤发生。本文从分子和细胞水平对与1p缺失相关的结肠癌发生途径进行了综述。散发性结肠癌与高脂肪/低蔬菜/低微量营养素的西式饮食密切相关。我们还探讨了某些与饮食相关的化合物（如过量的疏水性胆汁酸、低水平的叶酸、烟酸、植物源性抗氧化剂及其他调节性化合物）可能如何影响导致染色体缺失的过程，以及如何影响因1p缺失而发生特异性改变的分子和细胞途径。
