Abstract
BackgroundWe previously reported a positive association between serum 25-hydroxyvitamin D (25(OH)D) and colorectal cancer risk. To further elucidate this association, we examined the molar ratio of 25(OH)D to vitamin D binding protein (DBP), the primary 25(OH)D transport protein, and whether DBP modified the association between 25(OH)D and colorectal cancer risk.MethodsIn a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, controls were 1∶1 matched to 416 colorectal cancer cases based on age and date of blood collection. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) for quartiles of 25(OH)D, DBP, and the molar ratio of 25(OH)D:DBP, a proxy for free, unbound circulating 25(OH)D.ResultsComparing highest to lowest quartiles, DBP was not associated with colorectal cancer risk (OR = 0.91; 95% CI: 0.58, 1.42, p for trend = 0.58); however, a positive risk association was observed for the molar ratio of 25(OH)D:DBP (OR = 1.44; 95% CI: 0.92, 2.26, p for trend = 0.04). In stratified analyses, the positive association between 25(OH)D and colorectal cancer was stronger among men with DBP levels above the median (OR = 1.89; 95% CI: 1.07, 3.36, p for trend = 0.01) than below the median (OR = 1.20; 95% CI: 0.68, 2.12, p for trend = 0.87), although the interaction was not statistically significant (p for interaction = 0.24).ConclusionCirculating DBP may influence the association between 25(OH)D and colorectal cancer in male smokers, with the suggestion of a stronger positive association in men with higher DBP concentrations. This finding should be examined in other populations, especially those that include women and non-smokers.
Highlights
Vitamin D is thought to protect against carcinogenesis through mechanisms that include promotion of cell differentiation and apoptosis, inhibition of cell proliferation, and modulation of inflammation and immunity [1,2]
The majority of vitamin D is produced in the skin by exposing 7-dehydrocholesterol to UVB radiation, it can be obtained from dietary sources including fatty fish, eggs, fortified dairy and cereal products and supplements. 25-Hydroxyvitamin D (25(OH)D) is the primary form of vitamin D in circulation and is considered the best indicator of an individual’s vitamin D status since it is an integrated measure of vitamin D obtained from diet, supplements, and sun exposure [3]
We previously reported a positive association between serum 25(OH)D and risk for colon and rectal cancers in the Alpha-Tocopherol, Beta-Carotene Prevention (ATBC) Study [12], and two randomized clinical trials showed no effect of vitamin D supplementation on colorectal cancer incidence
Summary
Vitamin D is thought to protect against carcinogenesis through mechanisms that include promotion of cell differentiation and apoptosis, inhibition of cell proliferation, and modulation of inflammation and immunity [1,2]. Exposing colon cancer cells to 1,25(OH)2D promotes cellular differentiation [6] and a higher serum concentration of 25(OH)D is linked to lower rates of colorectal epithelial cell proliferation [7]. We previously reported a positive association between serum 25(OH)D and risk for colon and rectal cancers in the Alpha-Tocopherol, Beta-Carotene Prevention (ATBC) Study [12], and two randomized clinical trials showed no effect of vitamin D supplementation on colorectal cancer incidence [13,14]. We previously reported a positive association between serum 25-hydroxyvitamin D (25(OH)D) and colorectal cancer risk. To further elucidate this association, we examined the molar ratio of 25(OH)D to vitamin D binding protein (DBP), the primary 25(OH)D transport protein, and whether DBP modified the association between 25(OH)D and colorectal cancer risk
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