Clinical Trial of Vitamin D3 to Reduce Cancer Risk in Postmenopausal Women

描述(申请人提供)：乳腺癌、结肠癌、直肠癌、卵巢癌、前列腺癌、胃癌、膀胱癌、食道癌、肾癌、肺癌、胰腺癌和子宫癌以及非霍奇金淋巴瘤和多发性骨髓瘤的癌症死亡率与局部太阳UV-B辐射之间呈负相关，UV-B辐射是维生素D的主要来源。维生素D的抗癌作用得到了体外、动物和流行病学研究的有力支持。虽然现在有大量证据表明低维生素D摄入量和低血清25-羟基维生素D(25OHD)会增加患各种癌症的风险，但还没有发现维生素D状态对所有癌症发病率的影响的报道。此外，还没有报道使用足以将血清25OHD提高到最佳水平并针对癌症结果的维生素D干预的随机临床试验。我们小组最近进行了一项基于人群的研究，以确定在健康的绝经后妇女中补充钙和维生素D3的抗骨折效果，表明维生素D3降低了所有癌症的发病率。这些发现需要通过一项以癌症发病率为主要结果变量的随机对照临床试验来证实。在这项应用中，我们建议测试在保持足够的钙摄入量的同时，将血清25OHD增加到最佳水平，是否可以在60岁以上的绝经后妇女的人群样本中降低癌症的发生率。具体目标是：1.从内布拉斯加州邻近的9个县随机抽取60岁及以上独立生活的健康绝经后妇女群体；2.将2300名妇女纳入一项干预研究，将她们随机分配到两个治疗组中的一个：1)维生素D3(2000天/日)和钙(1200毫克/天)，或2)维生素D3安慰剂和钙安慰剂，并对每个受试者进行4年的跟踪调查；3.收集并储存每个受试者的白细胞，以检测遗传标记，如果干预被发现有效降低癌症发病率的话；4.确定补充维生素D3对所有类型癌症的综合发病率的影响；5.在嵌套病例对照研究中，确定随机收集的血清25OHD和研究第一年结束时与4年以上癌症风险的关系。在每半年一次的访问中，将对以下情况进行评估：病史和社会史；不良事件；癌症诊断；坚持服用补充剂/安慰剂。每年，我们将获得身高和体重，并在基线和随访结束时分析血清25OHD和1，25-二羟基维生素D，我们将评估饮食摄入量和体力活动。这项拟议的研究涉及NCI战略计划的目标，即“在2015年前消除癌症带来的痛苦和死亡。”它特别针对战略目标2，即“加快癌症预防工作的进展”。我们建议的营养干预研究的积极结果将导致一种廉价、安全的癌症预防方法。

DESCRIPTION (provided by applicant): An inverse correlation between cancer mortality rates and regional solar UV-B radiation exposure, a major source of vitamin D, has been found for cancers of the breast, colon, rectum, ovary; prostate, stomach, bladder, esophagus, kidney, lung, pancreas, and uterus, as well as non-Hodgkins lymphoma, and multiple myeloma. The anticancer effect of vitamin D is strongly supported by in vitro, animal, and epidemiological studies. Although a large body of evidence now links low vitamin D intake and low serum 25- hydroxyvitamin D (25OHD) to increased risk of various types of cancer, no reports were found of the effects of vitamin D status on all-cancer incidence. Furthermore, no randomized clinical trials have been reported that used a vitamin D intervention sufficient to raise serum 25OHD to optimum levels and that targeted a cancer outcome. A recent population-based study done by our group to determine the anti-fracture efficacy of calcium and vitamin D3 supplementation in healthy postmenopausal women demonstrated that vitamin D3 reduces all-cancer incidence. These findings need to be confirmed with a randomized controlled clinical trial designed with incidence of cancer as the primary outcome variable. In this application we propose to test whether increasing serum 25OHD to optimal levels, while maintaining adequate calcium intake, reduces the incidence of cancer in a population-based sample of postmenopausal women 60+ years of age. The Specific Aims are to: 1. Sample randomly the population of healthy independently-living postmenopausal women 60 years and older from 9 adjacent rural counties in Nebraska; 2. Enroll 2300 women into an intervention study, assign them randomly to 1 of 2 treatment groups: 1) vitamin D3 (2000 ID/d) and calcium (1200 mg/d), or 2) vitamin D3 placebo and calcium placebo, and to follow each subject for 4 years; 3. Collect and store white blood cells from every subject to test for genetic markers should the intervention be found effective in decreasing the incidence of cancer; 4. Determine the effect of supplementation with vitamin D3on incidence of all types of cancer combined; 5. Determine in a nested-case control study the association of serum 25OHD collected at randomization and at the end of year 1 of study with risk of cancer over 4 years. At each semiannual visit, the following will be assessed: medical and social history; adverse events; cancer diagnoses; and adherence to supplement/placebo. Annually, we will obtain height and weight and analyze serum 25OHD and1,25-dihydroxyvitamin D. At baseline and end of follow-up, we will assess dietary intake and physical activity. The proposed study addresses the goal of NCI's Strategic Plan to "eliminate the suffering and death due to cancer by 2015." It specifically addresses Strategic Objective 2, to "accelerate progress in cancer prevention." Positive findings from our proposed nutritional intervention study will result in an inexpensive, safe method of preventing cancer.