Abstract
Background: Many studies have demonstrated the relationship between vitamin D and cancer of many different sites, including of the breast, colorectum, prostate and lung. Most epidemiological studies have assessed the effects of dietary intake only, although endogenous production after sun exposure is the main source of vitamin D. The aim of our pilot study was to study serum levels of vitamin D in general population and in patients with different type of cancer. Patients and Methods: The control group consisted of 214 healthy individuals. Pathological groups of patients included 170 patients with different cancer types (28 patients with prostate cancer, 43 patients with breast cancer, 49 patients with colorectal cancer and 50 patients with lung cancer). All of the patients were enrolled in the early clinical stage of cancer up to clinical stage III. Advanced stages were not included into the study. Vitamin D serum levels were measured using ECLIA Roche method. Results: All the results for serum vitamin D from pathological groups were significantly lower compared to the levels of the control group. All the cancer types had a high incidence rate of very low serum levels of vitamin D. Lung cancer had the highest incidence rate of very low vitamin D serum levels. Conclusion: We found a high incidence of hypovitaminosis D in cancer patients compared to a healthy control group among a Czech population. This incidence rate is higher in comparison to data found in literature from the other parts of the world. Based on the data from this study, a large epidemiological study monitoring vitamin D serum levels in the healthy population and in cancer patients in the Czech Republic has been already proposed.
Vitamin D, especially in it's biologically most active form calcitriol (1,25-dihydroxyvitamin D3) is essential for the formation, growth, and repair of bones, for normal calcium absorption and for immune function. It is obtained primarily through exposure of the skin to ultraviolet radiation in sunlight, but it can also be obtained from some foods and dietary supplements. Vitamin D and its metabolites have always been important for treating vitamin D deficiency and disorders related to abnormal calcium homeostasis. But, association with other pathological abnormalities, particularly with cancer, has been also reported (1). The aim of our pilot study was to study serum levels of vitamin D in general population and in patients with different type of cancer.
Patients and Methods
Groups of patients. The control group: consisted of 214 healthy individuals. All of them underwent a complete medical examination. At the time of blood collection, there was no evidence of cancer or inflammatory disease in these people. Pathological groups of patients included 170 patients: 28 patients with prostate cancer, 43 patients with breast cancer, 49 patients with colorectal cancer and 50 patients with lung cancer. For their detailed descriptive statistic data see Table I. All of the patients were enrolled in the early clinical stage of cancer up to clinical stage III. Advanced stages were not included in the study. Serum samples were collected prior to any surgery. At this time patients have no oncological therapy and no vitamin D supplementation.
Descriptive statistics of the patient groups.
Laboratory methods. Blood for the laboratory analysis was collected from the cubital vein in the morning after an 8-hour fasting period. Sera were separated at 1700× g far 10 min. Vitamin D serum levels were measured using the ECLIA Roche method (2). Serum samples were stored in aliquots at −80°C until the measurement.
Statistical analysis. Descriptive statistics for vitamin D concentrations (N, median, min, max), for vitamin D concentrations categorized below low threshold, normal, above high (absolute and relative frequencies) were calculated. Descriptive statistics is also presented for age and gender. The statistical testing was done as two-tailed on the significance level of 5% for each testing. The pair-vise comparison of groups was done using Wilcoxon-Rank-Sum test because assumption of normality was remarkably violated for vitamin D concentrations. The test-for-trend option was selected in the chi-square test for comparison of categorized vitamin D concentrations (below low threshold, normal, above high) between groups.
Results
Results of serum levels of vitamin D are shown in Table II. It demonstrates that all the results from pathological groups are significantly lower compared to the levels of control group (p<0.0001 for all cancer by means of Wilcoxon-Rank-Sum test). There is a high incidence rate of very low serum levels in all the cancer groups. Table III shows the incidence of very low and low vitamin D serum levels as being significantly higher in cancer groups than in control group (p<0.0001 for all cancer by means of χ2-trend-test). There were no significant differences between the individual cancer groups found except for lung cancer (also with p<0.0001). This group significantly differed from the other cancer groups.
Discussion
The Czech Republic is the first country in terms of colorectal cancer incidence worldwide. The incidence of other malignant diseases is also very high. Moreover the Pilsner region has the highest incidence rate of all the cancer types in the Czech Republic. Therefore intensive research is targeted to the detailed description of potential mechanisms far this in order to use the result for the effective prevention of this disease. The first epidemiological studies from the 1940s demonstrated an inverse relationship between sunlight exposure levels in a given geographic area and the rates of incidence and death for certain types of non-skin cancer in that area. Because sunlight/UV exposure is necessary for the production of vitamin D, researchers hypothesized that variation in vitamin D levels accounted for the observed relationships (3-5). But the main focus on this issue can be dated to the end of the last century. Garland and Garland have been particularly dedicated to the problem of the relationship between vitamin D and cancer (6). The clinical use of vitamin D monitoring for colorectal cancer prevention has been described by Weinstein et al. (7), Feskanich et al. (8) and Ng et al. (9); for pancreatic cancer by Axanova et al. (10), Chiang and Chen (11); for breast cancer prevention by Colston and Hansen (12), Bertone-Johnson et al. (13), Welsh (14) and Shin et al. (15), and for prostate cancer by Chen and Holick (16). We have found that the low serum levels of vitamin D in cancer groups are more frequent, even in the early disease stages when compared with literature data. This can be explained by the higher incidence rate of cancer disease in the Czech Republic as well. The alarming results for the group with lung cancer supported our decision to initiate systematic vitamin D supplementation in accordance with literature guidelines. This decision was also supported by the report that low serum levels of vitamin D may diminish chemotherapy effect, described by Pelczynska et al. (17). Regular serum vitamin D monitoring every three months has also been implemented. Based on this pilot study and based on literature data (18, 19), vitamin D supplementation has been considered as a component of adjuvant therapy for colorectal cancer patients.
Serum levels of 25 (OH) vitamin D.
Incidence rate of different serum levels of 25 (OH) vitamin D in individual cancer types.
Conclusion
Considerable data of some preclinical studies suggest that there is a role for vitamin D in cancer therapy and prevention. Most of the studies report epidemiological data; no well–designed clinical trials of optimal administration of vitamin D as a cancer therapy have ever been conducted.
We found a high incidence of hypovitaminosis D in cancer patients compared with a healthy control group among the Czech population. This rate is higher in comparison to data found in literature for other parts of the world. Based on the data from this pilot study a large epidemiological study monitoring vitamin D serum levels in the healthy population and in cancer patients in the Czech Republic has already been proposed.
Acknowledgements
This study was supported by VZ MSM 0021620819 and grants NS9727, NS10258, NT11017, NS1023 and NS10253.
- Received July 4, 2011.
- Revision received August 18, 2011.
- Accepted August 19, 2011.
- Copyright© 2011 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
