Serum 25-Hydroxyvitamin D and Risks of Colon and Rectal Cancer in Finnish Men

Stephanie J. Weinstein; Kai Yu; Ronald L. Horst; Jason Ashby; Jarmo Virtamo; Demetrius Albanes

Disclosures

Am J Epidemiol. 2011;173(5):499-508. 

In This Article

Results

Colon cancer cases had significantly higher average weight and body mass index and a lower serum β-carotene concentration than their respective controls, while rectal cancer cases did not differ from controls with respect to any of the baseline characteristics (Table 1). When colon and rectal cancer cases were combined, colorectal cancer cases had significantly higher weight (P = 0.04) and a lower serum β-carotene concentration (P = 0.0004) than controls. Both colon and rectal cancer cases had nonsignificantly higher 25(OH)D concentrations than controls (9.5% (P = 0.14) and 10.9% (P = 0.63), respectively).

Figure 1 shows the expected seasonal variation in 25(OH)D concentrations, with values decreasing through the fall, being lowest in the winter months, and rising in late spring and early summer. There was substantial between-subject variation, however, such that high and low 25(OH)D concentrations were evident throughout the year. The median 25(OH)D concentration among controls with blood drawn in the darker months (November–April) was 27.8 nmol/L (interquartile range, 17.9–42.3), with a corresponding value for the sunnier months (May–October) of 41.7 nmol/L (interquartile range, 29.3–56.1). Serum was collected from few ATBC Study participants in June and August, and none was collected during July.

Figure 1.

Serum 25-hydroxyvitamin D (25(OH)D) concentrations according to calendar week of blood collection in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, Finland, 1985–2005. Each circle represents an individual 25(OH)D measurement, and the smoothed line shows the predicted 25(OH)D values calculated using locally weighted polynomial regression. Results were obtained among 1,221 controls (including colorectal controls) from several ATBC nested substudies with blood samples assayed in the same laboratory at the same time.

We observed no significant association between 25(OH)D concentration and colorectal, colon, or rectal cancer using the a priori defined cutpoints (Table 2), although the general pattern was for reduced risks within the lower 25(OH)D categories. Compared with the referent group, men with a 25(OH)D concentration less than 25 nmol/L had an approximately 30% lower colorectal cancer risk that was nearly statistically significant. The odds ratios comparing the highest 25(OH)D category (>75 nmol/L) with the lowest (<25 nmol/L) were 1.47 (95% CI: 0.72, 3.01), 2.28 (95% CI: 0.77, 6.78), and 1.19 (95% CI: 0.43, 3.28) for colorectal cancer, colon cancer, and rectal cancer, respectively. Combining distal colon cancer cases and rectal cancer cases produced patterns similar to those presented in Table 2 (data not shown), and there were few differences by season of blood collection in any of these models (Table 2).

Based on season-specific quartiles, the risk of colon cancer was significantly elevated for higher 25(OH)D concentrations (P trend = 0.01; Table 3), with a similar pattern being observed for colorectal cancer (P trend = 0.02; data not shown). Elevated colon cancer risk was also noted for the higher quartiles in the season-standardized models (Table 3), although the colorectal cancer association was weaker (P trend = 0.12; data not shown). These risk patterns for colon cancer were similar for subjects with blood drawn during the darker months and subjects with blood drawn during the sunnier months, but only in the darker months were the associations statistically significant (in the season-specific and season-standardized models, odds ratios for the highest quartile versus the lowest were 2.26 (95% confidence interval (CI): 1.12, 4.57; P trend = 0.03) and 2.10 (95% CI: 1.08, 4.10; P trend = 0.08), respectively). Threshold relations were suggested whereby subjects in the lowest quartiles had the lowest colon cancer risk. The rectal cancer association was generally null in the season-specific, season-standardized, and season-stratified (not shown) models, although the odds ratios for the second quartile versus the first quartile were significantly reduced (Table 3).

Exploratory stratum-specific subgroup analyses for colon cancer indicated greater elevated risk for the highest season-specific quartile versus the lowest among older men (i.e., age >57 years; odds ratio (OR) = 2.13, 95% CI: 1.03, 4.39) and subjects in the α-tocopherol supplementation arm (OR = 2.67, 95% CI: 1.21, 5.88). For rectal cancer, risk appeared greater for the highest quartile among men with higher serum β-carotene concentrations (≥185 μg/L; OR = 1.74, 95% CI: 0.69, 4.37) and those in the β-carotene supplementation arm (OR = 1.66, 95% CI: 0.68, 4.04). None of the tests for interaction by stratum were statistically significant, however. Risk of rectal cancer (but not colon cancer) appeared to differ on the basis of follow-up year of case diagnosis (highest quartile vs. lowest: for cases diagnosed through November 1999, OR = 2.24, 95% CI: 0.75, 6.67; for cases diagnosed after November 1999, OR = 0.59, 95% CI: 0.23, 1.52). However, this interaction was not statistically significant (P = 0.13).

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