Djuric Zora, Turgeon D Kim, Ren Jianwei, Neilson Andrew, Plegue Missy, Waters Ian G, Chan Alexander, Askew Leah M, Ruffin Mack T, Sen Ananda, Brenner Dean E
a Department of Family Medicine and Department of Environmental Health Sciences , University of Michigan , Ann Arbor , Michigan , USA.
Nutr Cancer. 2015;67(5):721-9. doi: 10.1080/01635581.2015.1029637. Epub 2015 Apr 14.
This randomized trial evaluated the effects of intervention with either a Healthy Eating or a Mediterranean diet on colon biomarkers in 120 healthy individuals at increased colon cancer risk. The hypothesis was that eicosanoids and markers of proliferation would be favorably affected by the Mediterranean diet. Colon epithelial biopsy tissues and blood samples were obtained at baseline and after 6 mo of intervention. Colonic eicosanoid concentrations were evaluated by HPLC-MS-MS, and measures of epithelial proliferation and nuclear morphology were evaluated by image analysis of biopsy sections. There was little change in proinflammatory eicosanoids and in plasma cytokine concentrations with either dietary intervention. There was, however, a 50% increase in colonic prostaglandin E3 (PGE3), which is formed from eicosapentanoic acid, in the Mediterranean arm. Unlike PGE2, PGE3, was not significantly affected by regular use of non-steroidal anti-inflammatory drugs at baseline, and normal weight subjects had significantly higher colon PGE3 than overweight or obese subjects. Increased proliferation in the colon at baseline, by Ki67 labeling, was associated with morphological features that defined smaller nuclei in the epithelial cells, lower colon leukotriene concentrations and higher plasma cytokine concentrations. Dietary intervention had little effect on measures of epithelial proliferation or of nuclear morphology. The increase in PGE3 with a Mediterranean diet indicates that in normal colon, diet might affect protective pathways to a greater extent than proinflammatory and proliferative pathways. Hence, biomarkers from cancer models might not be relevant in a true prevention setting.
这项随机试验评估了健康饮食或地中海饮食干预对120名患结肠癌风险增加的健康个体结肠生物标志物的影响。假设是地中海饮食会对类花生酸和增殖标志物产生有利影响。在基线和干预6个月后获取结肠上皮活检组织和血样。通过高效液相色谱-串联质谱法评估结肠类花生酸浓度，通过对活检切片进行图像分析评估上皮增殖和核形态学指标。两种饮食干预对促炎类花生酸和血浆细胞因子浓度几乎没有影响。然而，在地中海饮食组中，由二十碳五烯酸形成的结肠前列腺素E3（PGE3）增加了50%。与PGE2不同，PGE3在基线时不受常规使用非甾体抗炎药的显著影响，正常体重受试者的结肠PGE3显著高于超重或肥胖受试者。通过Ki67标记，基线时结肠增殖增加与上皮细胞核较小、结肠白三烯浓度较低和血浆细胞因子浓度较高的形态学特征相关。饮食干预对上皮增殖或核形态学指标影响很小。地中海饮食使PGE3增加表明，在正常结肠中，饮食对保护途径的影响可能比对促炎和增殖途径的影响更大。因此，癌症模型中的生物标志物在真正的预防环境中可能并不相关。
