CAROTENOID RICH DIET TRIAL TO REVERSE CIN II

一些营养素和饮食因素似乎是重要的， 子宫颈癌的风险。流行病学证据 研究强烈支持强调水果的饮食， 蔬菜，其中提供类胡萝卜素的一系列营养素 和其他可能的保护因素，在促进回归， 宫颈上皮内瘤变（CIN）。以前的试验或 扭转宫颈发育不良的干预措施主要集中在 药物或膳食补充剂，但大多数 最有前途和研究最少的潜在化学预防策略是 饮食.这项研究的主要目的是确定类胡萝卜素- 富含水果和蔬菜的饮食会促进 CIN I和CIN II的消退率增加。为了 了解饮食干预的潜在机制， 次要目的是：确定CIN I和II的消退是否 反映在人类病毒基因组拷贝数的调节中， 乳头状瘤病毒（HPV）和HPV E6/E7表达;并确定是否 CIN I和II的消退与以下表达相关： 视黄酸受体（RAR）和/或类视黄醇X受体（RXR）。HPV 已明确确定为CIN的致病因子，因此， 了解饮食对HPV的影响是至关重要的， 作用机制。生物效应可以通过结合 特异性核蛋白受体RAR和RXR这些受体 调节特定靶基因的表达，因此，它们具有 研究了可能的作用机制。为了 为了达到上述目的，一项富含类胡萝卜素饮食的临床试验 建议在326名CIN I妇女中， 和二.主要终点将是CIN的完全消退， 基于基线和研究结束时采集的活检标本。的 回归率将在这些妇女之间进行比较， 饮食干预与妇女继续他们的日常饮食。的 样本量的确定是假设基础自发回归 率为25%，脱落率为30%（主要是不依从）， HPV类型（排除机制研究）和可用患者 人口应计。膳食摄入量将使用 Fred哈钦森食物频率问卷和7天食物记录。 研究治疗组的女性将接受个性化的 饮食咨询与行为策略，以促进饮食 变化饮食干预的目标是最简单的改变 来达到水果和蔬菜的摄入量， β-胡萝卜素>0.69，类胡萝卜素总量>2.01 μ mol/L。结果 这项研究可能使医生将饮食作为一种管理策略， 对于CIN，这将消除数百万消融的需要， 每只耳朵都要做的CIN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.