Participating VDPP cohorts and control characteristics are presented in . All participants were adults; the majority were over age 50 years. In most cohorts, blood samples were collected throughout the year, except CLUE II, in which samples were collected from May to November, and ATBC, in which only 7% of samples were collected during June and August and none were collected in July.
Characteristics (%) of Participants in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers, by Cohort
Participants came from Finland, Shanghai, China, and all major geographic regions of the United States. Seventy-two percent of participants were white, 4% were black, 18% were Asian, and 4% were of other race/ethnicity. In the ATBC, SMHS, and SWHS cohorts, approximately 20% of the population or more had very low 25(OH)D levels (<25 nmol/L). In the CLUE II, CPS-II, and HPFS cohorts, more than 20% of the population had 25(OH)D concentrations greater than or equal to 75 nmol/L.
illustrates the unadjusted distributions of circulating 25(OH)D by country. Vertical lines show cutpoints used in the analyses. The distribution of 25(OH)D concentrations was slightly higher among men in the United States (, part A) and China (, part B) than among women in these countries. The median 25(OH)D levels among men and women in the United States were 58.4 nmol/L and 51.7 nmol/L, and in China they were 38.0 nmol/L and 33.1 nmol/L, respectively. The ATBC Study, which included only Finnish men, had the lowest vitamin D status of all cohorts (median concentration, 31.9 nmol/L) (, part C).
Figure 1. Distribution of circulating 25-hydroxyvitamin D (25(OH)D) concentrations by country within the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. A) Distribution of circulating 25(OH)D concentrations among US men and women. Vertical lines represent (more ...)
illustrates the distribution of circulating 25(OH)D by race/ethnicity, season of blood draw, and latitude. In whites (, part A), 25(OH)D concentrations were lowest in all seasons among persons living at latitudes greater than 42°N and highest among those living at latitudes lower than 35°N. The amplitude of seasonal differences was most marked among whites living in the North, although seasonal differences were statistically significant in each latitude stratum. In blacks (n = 188; , part B), mean concentrations did not vary within season by 2 latitude strata, except that those living in the South (<35°N latitude) had borderline-significantly different circulating 25(OH)D according to season (P = 0.06). Among Asians (n = 871) and persons of “other” race/ethnicity (n = 188) (, part C), statistically significant differences in circulating 25(OH)D were observed by season; these subgroups could not be examined by latitude because of a lack of geographic diversity.
Figure 2. Mean circulating 25-hydroxyvitamin D (25(OH)D) concentrations by race/ethnicity, season, and latitude within the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Circles represent mean values; bars represent the standard error. A) 25(OH)D (more ...)
provides unadjusted summary data for potential correlates analyzed according to a priori 25(OH)D cutpoints. Higher percentages of black and Asian participants had 25(OH)D concentrations less than 25 nmol/L as compared with whites and persons of “other” race/ethnicity. The prevalence of 25(OH)D concentrations less than 25 nmol/L was highest among persons who had had blood drawn in the winter. Circulating 25(OH)D concentrations also varied by alcohol consumption, body mass index, use of hormone replacement therapy, education, history of diabetes, history of hypertension, cigarette smoking, physical activity, and use of nutritional supplements.
Distribution of Participant Characteristics According to A Priori 25-Hydroxyvitamin D Category in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancersa
Results from the stepwise regression models are presented in . Variables positively associated with circulating 25(OH)D concentrations among all controls were male sex, summer blood draw (vs. fall), vigorous physical activity (vs. light activity), current alcohol use (vs. none), vitamin D intake, fish intake, and current use of calcium and multivitamin supplements (vs. no current use). Variables associated with lower circulating 25(OH)D were body mass index, winter and spring blood draw (vs. fall), history of diabetes, sedentary physical activity (vs. light activity), current smoking (vs. never smoking), and black and “other” race/ethnicity (vs. white). Together, these variables explained 30% of the variation in 25(OH)D concentrations. Models limited to US-only participants yielded similar findings, except that intake of milk (which is fortified with vitamin D in the United States) was a predictor while fish intake was not (data not shown).
Variables Associated With Circulating 25-Hydroxyvitamin D Concentrations (nmol/L) Among Controls in Stepwise Regression Models, Overall and by Sex and Race/Ethnicity, Cohort Consortium Vitamin D Pooling Project of Rarer Cancersa
Results from stepwise regression models stratified by sex and race/ethnicity are also shown in . Predictors in men and women varied slightly: Only the category of obesity (body mass index ≥30) was associated with significantly lower concentrations in men; a linear association with body mass index was observed among women. Associations with physical activity, smoking, vitamin use, and dietary sources varied between the sexes. In whites, who comprised 72% of the total sample population, statistically significant predictors were the same as those for the entire population. Among blacks, only male sex, summer blood draw, dietary calcium intake, and current multivitamin use remained in the model; all were positively associated with circulating 25(OH)D. Among Asians, male sex, summer blood draw, and current alcohol use were positively associated with 25(OH)D concentrations, while winter and spring blood draw (vs. fall), current smoking, and dietary calcium and vitamin D intakes were inversely related.
presents results from stepwise regression analyses stratified by season of blood draw. Male sex and dietary vitamin D intake were positively associated and body mass index and black race/ethnicity were inversely associated with 25(OH)D concentrations in every season. The adjusted r2 value for winter was 32%, whereas the summer model explained only 16% of the variation in 25(OH)D concentrations. In the winter, as opposed to the summer (when sun exposure would be expected to dominate 25(OH)D status), cigarette smoking and a high school education were inversely associated with circulating 25(OH)D concentrations and fish intake and multivitamin use were positively associated.
Variables Associated With Circulating 25-Hydroxyvitamin D Concentrations (nmol/L) Among Controls in Stepwise Regression Models According to Season of Blood Draw, Cohort Consortium Vitamin D Pooling Project of Rarer Cancersa
In the subset of 4 cohorts with data on dose of supplemental vitamin D and calcium (ATBC, CPS-II, NHS, and PLCO), both total vitamin D intake (12.7-nmol increase/1,000 IU) and fish intake (6.1-nmol/L increase per 100 g) remained in the model. The Spearman correlation between 25(OH)D and dietary vitamin D intake (all cohorts) was 0.22 (P < 0.0001), and for total vitamin D intake (4 cohorts) it was 0.29 (P < 0.0001). In the 5 cohorts with information on hair color and eye color (ATBC, HPFS, MEC, SMHS, and SWHS), these variables did not remain in the final model, and race/ethnicity remained a statistically significant predictor.
displays predictors of 25(OH)D concentrations for the categories <25, 25–<50, and ≥75 nmol/L. The statistically significant predictors of very low 25(OH)D concentrations (<25 nmol/L) were black race/ethnicity, low vitamin D intake, female sex, obesity, sedentary behavior, and winter blood draw. Factors inversely associated with very low concentrations of 25(OH)D included Asian race/ethnicity, calcium supplement use, multivitamin use, and alcohol consumption. Predictors of 25(OH)D concentrations between 25 nmol/L and 49.9 nmol/L were similar to those for <25 nmol/L, but the associations were weaker. Vigorous physical activity was positively associated with higher 25(OH)D concentrations (≥75 nmol/L), while obesity and low dietary vitamin D intake were inversely associated. Current use of calcium and multivitamin supplements, male sex, and summer blood draw were associated with a borderline-significantly higher likelihood of greater 25(OH)D concentrations.
Odds Ratios for the Association Between Selected Covariates and Circulating 25-Hydroxyvitamin D Concentrations, Cohort Consortium Vitamin D Pooling Project of Rarer Cancersa