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serum 25OHD level against risk for colorectal cancer that correlated with each 2.5 nmol/L increase, although there was significant between-study heterogeneity. The results did not significantly differ by gender, mean population age, or cancer subsite (colon or rectum). The review noted that, based on multiple studies of circulating 25OHD and colorectal cancer risk, individuals in the high quartile or quintile of 25OHD level had about half the risk of colorectal cancer as did those in the lowest group. In another systematic review of studies examining associations between serum 25OHD levels and colorectal cancer, Bischoff-Ferrari et al. (2006a) concluded that the protective effect of 25OHD for decreased risk of colorectal cancers began at 75 nmol/L, and optimal levels were between 90 and 100 nmol/L. In contrast to these findings, the AHRQ-Ottawa systematic review reported that the studies reviewed were too inconsistent to permit conclusions to be drawn about specific serum 25OHD levels that conferred a decrease in risk.

Colorectal adenomas/polyps The AHRQ-Tufts systematic review considered evidence for associations between 25OHD levels and risk for colorectal adenomas. Colorectal adenomas or polyps are precursor lesions for colon cancer, and a number of investigations focused on the influence of vitamin D or calcium on the incidence of these surrogate markers for human colon carcinogenesis. A meta-analysis by Wei et al. (2008) of seven studies suggested that at the upper quintiles of circulating 25OHD levels there was a significant decrease in risk for colorectal adenoma. In parallel, these authors conducted a meta-analysis of vitamin D intake and colorectal adenoma risk in seven cohort and five case–control studies and found a marginally significant (11 percent) decreased risk among persons with high compared with low vitamin D intakes. The cut-points for the highest category of vitamin D intake varied between studies, with about one-third of the studies reporting cut-points of approximately 600 IU/day, one-third reporting cut-points between 250 and 600 IU/day, and one-third reporting cut-points of below 250 IU/day.

Stronger evidence has accumulated for a role of dietary calcium. The AHRQ-Tufts analysis identified four good quality cohort studies that evaluated the association between calcium intake and risk for colorectal adenoma. Two of these studies recruited men and women with a history of previous colorectal adenoma. One study found a significant inverse association between total calcium intake and colorectal adenoma recurrence after an average of 3.1 years of follow-up (highest [> 1,279 mg/day] vs. lowest [< 778 mg/day]) intake, whereas another found no significant association. Among two studies of healthy women without a history of colorectal adenoma one found a significant inverse association between total calcium intake and colorectal adenoma (highest vs. lowest intake, whereas the other found a borderline significant trend (highest [median, 1,451 mg/day] vs. lowest [median, 584 mg/day] intake. A Cochrane systematic review identified two randomized trials that found that calcium supplementation

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