Stephanie J. Weinstein, M.S., Ph.D.  Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH 

Vitamin D and Colorectal Cancer Risk – What is the Correlation? Interview with:

Stephanie J. Weinstein, M.S., Ph.D.  Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH 

Dr. Weinstein

Stephanie J. Weinstein, M.S., Ph.D. 
Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics
National Cancer Institute, NIH What is the background for this study?  

Response: Vitamin D, known for its role in maintaining bone health, is hypothesized to lower colorectal cancer risk via several pathways related to cell growth and regulation. Previous prospective studies have reported inconsistent results for whether higher concentrations of circulating 25-hydroxyvitamin D, the accepted measure of vitamin D status, are linked to lower risk of colorectal cancer. The few randomized clinical trials of vitamin D supplementation and colorectal cancer completed thus far have not shown an effect; but study size, relatively short supplementation duration, and only moderate compliance may have contributed to their null findings.

To address inconsistencies in prior studies on vitamin D, and to investigate associations in population subgroups, we harmonized and analyzed participant-level data from over 5,700 colorectal cancer cases who had blood collected before colorectal cancer diagnosis, and 7,100 matched cancer-free controls. Study participants were drawn from 17 prospective cohorts from the United States, Europe, and Asia and were followed for an average of 5.5 years (range: 1 – 25 years). We used a single, widely accepted assay and laboratory for new vitamin D measurements and calibrated existing vitamin D measurements. In the past, substantial differences between assays made it difficult to integrate vitamin D data from different studies. Our novel calibration approach enabled us to explore risk systematically over the broad range of vitamin D levels seen internationally. What are the main findings?

Response: We found that higher circulating vitamin D concentrations were significantly associated with lower colorectal cancer risk. Our findings indicate that, compared to participants with vitamin D concentrations between 50- <62.5 nmol/L, those who had vitamin D concentrations <30 nmol/L had a 31% higher risk of colorectal cancer during follow-up. Similarly, participants with concentrations between 75 and <100 nmol/L had a 22% lower risk. However, there was no benefit at concentrations of 100 nmol/L or greater. These associations persisted even after adjusting for known colorectal cancer risk factors. Protective associations were seen in all subgroups examined; however, the association was noticeably stronger in women than men at concentrations above 75 nmol/L. What should readers take away from your report?

Response: Our international collaboration shows that higher circulating vitamin D concentrations are significantly associated with reduced colorectal cancer risk. This study strengthens the evidence, previously considered inconclusive, for a protective relationship between vitamin D concentrations and colorectal cancer, and contributes to the body of evidence to be considered when determining vitamin D recommendations.

Our research examined the relation between blood vitamin D concentrations and risk of colorectal cancer in people who did not have cancer at the beginning of the study. Our study did not address the potential benefits or possible harms of vitamin D supplements for healthy participants nor for colorectal cancer patients. The study also did not examine the effect of changes in vitamin D concentrations on the development of colorectal cancer. What recommendations do you have for future research as a result of this work?

Other areas for study include an evaluation of health effects of very high vitamin D concentrations, an examination of whether these associations vary by genetic factors, and a more thorough investigation of associations in other racial/ethnic groups. An evaluation of whether vitamin D affects survival in individuals with cancer is another area of interest. Ongoing clinical trials will contribute additional information that may generate other research questions. Because trials usually examine only one dose, in a select population over a relatively short time, the results of both prospective cohort studies and trials provide complementary information. Is there anything else you would like to add?

Response: Vitamin D can be obtained in the diet (particularly from fortified foods), from supplements, and from sun exposure. Good sources include foods such as fatty fish and eggs that naturally contain vitamin D, and milk, yogurt, margarine, juices, and breakfast cereals that are fortified with vitamin D. Experts recommend vitamin D be obtained through diet whenever possible because excessive ultraviolet radiation is a major risk factor for skin cancer.

One issue readers should be aware of is that, effective July 26, 2018, the Daily Value for vitamin D intake will increase from 400 IU (10 µg) to 800 IU (20 µg). Also, the units used on the food label will change from IU to µg (1 µg vitamin D = 40 IU). This adds an additional challenge when comparing the vitamin D content of various foods. Because various regulations currently set limits on how much vitamin D can be added to particular foods, certain foods may no longer be considered “good” or “excellent” sources of vitamin D even though the actual amount of vitamin D in that food may not have changed.

Another issue readers should be aware of is that there are different units used to measure circulating 25-hydroxyvitamin D concentrations. Many published research papers (but not all) now report vitamin D concentrations in nmol/L. Some older papers and most clinical laboratories, where a patient may have their blood vitamin D measured, report values in ng/ml. To convert circulating vitamin D from nmol/L to ng/mL, divide values by 2.5. To convert circulating vitamin D from ng/ml to nmol/L, multiply values by 2.5. 


Circulating Vitamin D and Colorectal Cancer Risk: An International Pooling Project of 17 Cohorts

Marjorie L McCullough Emilie S Zoltick Stephanie J Weinstein Veronika FedirkoMolin Wang Nancy R Cook A Heather Eliassen Anne Zeleniuch-JacquotteClaudia Agnoli Demetrius Albanes …

JNCI: Journal of the National Cancer Institute, djy087,

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Last Updated on July 9, 2018 by Marie Benz MD FAAD