CAROTENOID RICH DIET TRIAL TO REVERSE CIN II

几种营养素和饮食因素似乎在 确定患宫颈癌的风险。来自流行病学的证据 研究强烈支持强调水果和水果饮食的作用 蔬菜，在一系列营养素中提供类胡萝卜素 和其他可能的保护性因素，在促进退化的过程中 宫颈上皮内瘤变(CIN)。以前的试验或 逆转宫颈发育不良的干预措施主要集中在 药剂或膳食补充剂，但大多数 有希望但研究最少的潜在化学预防策略是 节食。这项研究的主要目的是确定一种类胡萝卜素- 富含水果和蔬菜的饮食会显著促进 提高CIN I和CIN II的消退率。为了 了解饮食干预的潜在机制， 次要目标是：确定CIN I和CIN 11的回归是否 反映在人类病毒基因组拷贝数的调节上 乳头瘤病毒(HPV)和HPVE6/E7的表达；并确定 CIN I和CIN II的消退与其基因的表达有关 视黄酸受体(RAR)和/或维甲酸X受体(RXR)。人类乳头瘤病毒 已被明确确定为CIN的病因，因此， 了解饮食对人乳头瘤病毒的影响是非常重要的。 作用机制。生物效应可以通过结合来调节。 结合特定的核蛋白受体RAR和RXR。这些受体 调节特定靶基因的表达，因此，它们具有 已列入其中，以探讨可能的行动机制。按顺序 为了实现上述目标，一项富含类胡萝卜素的饮食的临床试验 在326名患有CIN I的女性中，建议摄入高水果和蔬菜 和ii.主要终点将是CIN的完全回归， 基于基线和研究结束时采集的活检样本。这个 退化率将在这些女性之间进行比较 饮食干预与妇女继续日常饮食的对比。这个 样本量的确定假设为基本的自发回归 25%的比率，30%的辍学率(主要是不遵守)，10%的新奇 HPV类型(不包括机制研究)和可用的患者 应计项目的人口。膳食摄入量将使用 弗雷德·哈钦森食物频率问卷和7天食物记录。 接受研究治疗的女性将接受个性化治疗 以行为策略促进饮食的饮食咨询 改变。饮食干预的目标是最简单的改变 为了达到水果和蔬菜的摄入量，这将导致血浆 β胡萝卜素0.69和类胡萝卜素总和2.01umol/L。 这项研究可能使医生能够将饮食作为一种管理策略 对于CIN，这将消除数百万次消融的需要 对于CIN，每只耳朵都要做的手术。

Several nutrients and dietary factors appear to be important in determining risk for cervical cancer. Evidence from epidemiologic studies strongly supports a role for a diet emphasizing fruits and vegetables, which provides carotenoids among an array of nutrients and other possibly protective factors, in promoting the regression of cervical intraepithelial neoplasia (CIN). Previous trials or interventions to reverse cervical dysplasia have focused on pharmacologic agents or dietary supplementation, but the most promising and least studied potential chemopreventive strategy is diet. The primary aim of the study is to determine if a carotenoid- rich diet high in fruits and vegetables will promote a significant increase in the regression rate of CIN I and CIN II. In order to understand the potential mechanism of the dietary intervention, the secondary aims are: to determine if the regression of CIN I and ll is reflected in the modulation of viral genome copy number of human papilloma virus (HPV) and HPV E6/E7 expression; and to determine if the regression of CIN I and II is associated with expression of retinoic acid receptors (RAR) and/or retinoid X receptors (RXR). HPV has clearly been determined to be a causal agent for CIN, therefore, it is essential to understand the impact of diet on HPV as a possible mechanism of action. A biological effect may be mediated by binding to specific nuclear protein receptors, RAR and RXR. These receptors regulate expression of specific target genes, therefore, they have been included to explore the possible mechanism of action. In order to achieve the above aims, a clinical trial of a carotenoid-rich diet high in fruits and vegetables is proposed among 326 women with CIN I and II. The primary endpoint will be the complete regression of CIN, based on biopsy specimens taken at baseline and end of study. The rates of regression will be compared between those women on the dietary intervention versus women continuing their usual diet. The sample size was determined assuming a base spontaneous regression rate of 25%, a 30% dropout rate (primarily nonadherence), a 10% novel HPV type (precluding study of mechanism), and available patient population for accrual. Dietary intake will be measured using the Fred Hutchinson Food Frequency Questionnaire and 7-Day Food Records. The women on the treatment arm of study will receive individualized dietary counseling with behavioral tactics to facilitate dietary changes. The goal of the dietary intervention is the simplest changes to achieve a fruit and vegetable intake that will result in plasma betacarotene >0.69 and sum of carotenoids >2.01 umol/L. Findings of this study may enable physicians to use diet as a management strategy for CIN, which would eliminate the need for millions of ablative procedures that are done each ear for CIN.