Major Finding: People with more than 75 nmol/L of circulating 25-hydroxy-vitamin D (25-[OH]D) had a 40% lower risk of developing colorectal cancer over a mean 3.8 years of follow-up, compared with those with less than 25 nmol/L.
Data Source: A nested case-control investigation compared 1,248 participants in the EPIC study who developed first-incident colorectal cancer after enrollment and 1,248 healthy controls matched for age, sex, study center, menopausal status, and other characteristics.
Disclosures: The study was supported by a grant from the World Cancer Research Fund. None of the investigators reported having conflicts of interest.
Serum levels of vitamin D were inversely associated with colorectal cancer risk, according to findings from one of the first large investigations conducted in western European populations.
Participants with more than 75 nmol/L of circulating 25-hydroxy-vitamin D (25-[OH]D) had a 40% lower risk of developing colorectal cancer over a mean 3.8 years of follow-up, compared with those with less than 25 nmol/L, said Mazda Jenab, Ph.D., of the International Agency for Research on Cancer, Lyon, France, and colleagues.
“Higher circulating 25-(OH)D concentration was associated with lower colorectal risk in a dose-response manner,” they reported (BMJ 2010 Jan. 10 [doi:10.1136/bmj.b5500
The investigation “suggests that raising very low levels of 25-(OH)D to the mid-range may protect against colon cancer.”
The subjects were enrolled during 1992-1998 in the EPIC (European Prospective Investigation into Cancer and Nutrition) study, which includes 520,000 participants at 23 centers in 10 western European nations.
The nested case-control study looked at 1,248 participants in the EPIC study who developed first-incident colorectal cancer (CRC) after enrollment and 1,248 healthy controls matched for age, sex, study center, menopausal status, and other characteristics.
Dr. Douglas K. Rex commented in an interview, “This is the largest study to address this issue, and the results were consistent across a range of European countries.
The authors called for prospective, randomized, controlled trials of vitamin D supplementation, but the results seem strong enough that patients interested in lowering their risk of CRC can be informed that higher blood levels of 25-(OH)D are associated with risk reduction.” Dr. Rex is distinguished professor of medicine at Indiana University, Indianapolis, and director of endoscopy at Indiana University Hospital.
At enrollment, the researchers measured prediagnostic 25-(OH)D levels using blood samples analyzed by enzyme immunoassay, and gauged dietary intake of vitamin D and calcium using questionnaires.
Using blood sample data in addition to dietary intake data accounted for endogenous vitamin D production from sun exposure.
Multivariate analysis controlled for possible confounders including body mass index, physical activity, smoking, education, and intake of fruits, vegetables, meats, and alcohol.
In addition, the investigation results were adjusted for season of blood collection.
The participants in this observational study had a mean age of 58 years, and about half were men. They were divided into five groups based on their circulating vitamin D levels: less than 25 nmol/L, 25-50 nmol/L, 50-75 nmol/L (reference group), 75-100 nmol/L, and more than 100 nmol/L.
The incidence ratio for colorectal cancer was 1.32 for those in the lowest quintile, compared with 0.77 for those in the highest, a statistically significant difference. Those in the second-lowest quintile had an incidence ratio of 1.29 for colorectal cancer.
The association between serum 25-(OH)D and disease was stronger for colon cancer (1.90 vs. 0.71 for the lowest and highest quintiles, respectively) than for rectal cancer (0.77 vs. 0.82).
When the analysis was restricted to dietary intake, however, the researchers found that “higher consumption of dietary calcium, but not dietary vitamin D, was found to be associated with a reduced risk.” Participants with the lowest levels of dietary calcium had an incidence rate of 1.33, versus 0.95 in those with the highest dietary intake of calcium.
In addition, alcohol intake appeared to be a risk factor, as “the highest colorectal cancer risk was seen in those with the lowest circulating levels of 25-(OH)D and the highest level of alcohol consumption,” with an incidence rate of 1.46, compared with 0.82 in the group with the highest level of vitamin D and lowest alcohol intake.
One limitation of the study was the short follow-up time. “However, exclusion of cases with less than 2 years of follow-up did not alter any of the findings,” the researchers said.
Randomized trials are needed to “determine whether vitamin D has a causal role in colorectal cancer prevention or whether it is a marker of other events” before recommending vitamin D supplementation for this purpose, the authors noted.
“The potential cancer risk benefits of higher vitamin D levels should be balanced” against having caution for the toxic potential and the risk of serious adverse events, they added.