Meta-analysis of all available studies of serum 25(OH)D level with respect to a particular cancer is used to determine the dose-response relation for cancer incidence.
There are two observational approaches for ascertaining the role of vitamin D in the risk of cancer: case-control and nested case-control studies.
The primary difference between the two approaches is the time between serum 25(OH)D level determination and incidence of cancer: the lag time is essential zero for case-control studies but anywhere from several years to 28 years for nested case-control studies.
Only case-control studies consistently find inverse correlations between serum 25(OH)D level and cancer incidence for breast cancer1. Nested case-control studies generally do not find inverse correlations23.
However, those from Harvard have45 as do those for colorectal cancer6. In these studies, the lag between serum 25(OH)D level determination and cancer incidence was 2-4 years. The reason why short lag times may be important may be that once tumors reach a diameter of 1-3 mm, they generate a vascular system (angiogenesis) to obtain nutrients at a faster rate7. After that, tumors grow very rapidly8.
Results of the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP) were recently published2. The VDPP was comprised of ten cohort studies, seven from the United States, two from China, and one from Finland. There were anywhere from 516 to 1353 cases for each type of cancer. Those in the cohorts were observed for a mean follow up time of about ten years. Contrary to the results from numerous ecological studies, no beneficial effect of serum 25(OH)D level was found for the seven cancers studied: endometrial, esophageal, gastric, kidney, ovarian, and pancreatic cancer and NHL; in fact there was an increased odds ratio for pancreatic cancer at the highest serum 25(OH)D level. While it is difficult to determine why the results of the VDPP differ from both ecological studies for these types of cancer and from breast and colorectal cancer observational studies, it may be possible that the long follow up time rendered the serum 25(OH)D level from the time of enrollment inaccurate. For example, a study of Finnish smokers found lymphoma cases diagnosed less than 7 years from the baseline showed an inverse association (OR for highest vs. lowest tertile = 0.43; 95% CI: 0.23, 0.83; p for trend = 0.01), but not later diagnoses (OR = 1.52; 95% CI: 0.82, 2.80; p for trend = 0.17)3.
After the VDPP papers were published, an observational study from Finland found having serum 25(OH)D >57.8 nmol/L vs <57.8 nmol/ excluding cases who donated serum samples within 1–3 years of cancer diagnosis gave an adjusted OR 0.49 (0.24–1.01) for ovarian cancer11.
There has been one successful RCT of vitamin D supplementation with respect to cancer incidence. In a study involving post menopausal women living in Nebraska, those taking 1100 IU/day of vitamin D3 and 1450 mg/day of calcium had a 77% reduction in all-cancer incidence between the ends of the first and fourth years, while those taking only the calcium had a 40% risk reduction18. Calcium seems to reduce the risk of cancer independently from vitamin D19. Those taking vitamin D supplements in the Lappe et al. study increased their serum 25(OH)D levels from 29 ng/mL to 39 ng/mL.
An earlier RCT in England involving 100 000 IU oral vitamin D3 supplementation or matching placebo every four months (equivalent to 833 IU/day) over five years found an age-adjusted relative risk for cancer mortality of 0.93 (95% CI, 0.64-1.34) for males and 0.53 (0.21-1.33) for females20.
Page last edited: 04 May 2011
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