Clinical Trial of Vitamin D3 to Reduce Cancer Risk in Postmenopausal Women
Principal Investigator: Joan Lappe
Abstract: DESCRIPTION (provided by applicant): An inverse correlation between cancer mortality rates and regional solar UV-B radiation exposure, a major source of vitamin D (vit D), has been found for cancers of the breast, colon, rectum, ovary, prostate, stomach, and numerous other cancers. Dietary and serum studies also demonstrate that vit D is a risk factor in colonic adenomas and for numerous cancers. The anticancer effect of vit D is strongly supported by in vitro and animal studies. However, no randomized clinical trials have used a vit D intervention sufficient to raise serum 25OHD to optimum levels and have targeted a cancer outcome. We reported a double-blind, placebo-controlled, randomized trial of calcium (Ca) and vit D supplementation in a population-based sample of postmenopausal women. A secondary objective of that study was to determine the efficacy of Ca alone and of Ca plus vit D3 in reducing risk of cancer of all types. We found that vit D3 significantly reduced the risk of all-types cancer by 60%. These findings need to be confirmed with a clinical trial designed with incidence of cancer as the primary outcome. In this application we propose to test whether increasing serum 25OHD to optimal levels, while maintaining adequate Ca 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 rural counties;2. Enroll 2300 women into an intervention study, assign them randomly to 1 of 2 treatment groups: 1) vit D3 (2000 IU/d) and Ca (1200 mg/d), or 2) vit D3 placebo and Ca 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;4. Determine the effect of supplementation with vit D3 on incidence of all types of cancer combined;5. Determine in a nested-case control study the association of serum 25OHD collected at baseline and the end of year 1 with risk of cancer over 4 years;6. Determine the effect of supplementation with calcium and vit D3 on incidence of specific cancers: breast, lung, colon and myeloma, leukemia, lymphoma. 7. Determine the effect of supplementation on incidence of other disorders, specifically hypertension, cardiovascular disease, osteoarthritis, colonic adenomas and diabetes, upper respiratory infections and falls. At each 6-mo visit, we will assess: medical and social history;adverse events;cancer diagnoses;and adherence to supplement/placebo. Annually, we will obtain height and weight and analyze serum 25OHD. At baseline and end of 4 yrs, 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 nutritional intervention study will result in an inexpensive, safe method of preventing cancer. PUBLIC HEALTH RELEVANCE: Project Narrative The purpose of this project is to determine whether, in a rigorous clinical trial, vitamin D3 and calcium supplementation decreases risk of all types of cancer. Positive findings will provide support for health policy changes to promote optimal vitamin D levels in the population.
Funding Period: 2009-01-01 - 2014-11-30
more information: NIH RePORT
- Comprehensive association analysis of nine candidate genes with serum 25-hydroxy vitamin D levels among healthy Caucasian subjectsFeng Xiao Bu
Osteoporosis Research Center, Creighton University Medical Center, Creighton University, 601 N 30th St, Suite 6730, Omaha, NE 68131, USA
Hum Genet 128:549-56. 2010..The CYP2R1 gene and the GC gene remain significant in the pooled cohort. The results suggest that the CYP2R1 and GC genes may contribute to the variation of serum 25(OH)D levels in healthy populations...
- Factors predicting vitamin D response variation in non-Hispanic white postmenopausal womenLan Juan Zhao
Department of Biostatistics and Bioinformatics, Center for Bioinformatics and Genomics, Tulane University, New Orleans, Louisiana 70112, USA
J Clin Endocrinol Metab 97:2699-705. 2012..Understanding factors affecting the response variation is important for identifying subjects who are susceptible to vitamin D deficiency or toxicity. This study aimed to evaluate potential predictors for vitamin D response variation...
- DNA methylation levels of CYP2R1 and CYP24A1 predict vitamin D response variationYu Zhou
Center for Bioinformatics and Genomics, Department of Biostatistics and Bioinformatics, Tulane University, New Orleans, LA 70112, USA Cell and Molecular Biology Department, Tulane University, New Orleans, LA 70118, USA
J Steroid Biochem Mol Biol 144:207-14. 2014..Our findings indicate that baseline DNA methylation levels of CYP2R1 and CYP24A1 may predict vitamin D response variation. This article is part of a Special Issue entitled '16th Vitamin D Workshop'. ..