Circulating 25-hydroxyvitamin D and risk of non-hodgkin lymphoma: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers

Abstract

Case-control studies generally suggesting an inverse association between sun exposure and non-Hodgkin lymphoma (NHL) have led to speculation that vitamin D may protect against lymphomagenesis. To examine this hypothesis, the authors conducted a pooled investigation of circulating 25-hydroxyvitamin D (25(OH)D) and subsequent NHL risk within 10 cohorts participating in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. The authors analyzed measurements from 1,353 cases and 1,778 controls using conditional logistic regression and other methods to estimate the association of 25(OH)D with NHL. No clear evidence of association between categories of 25(OH)D concentration and NHL was observed overall (P(trend) = 0.68) or by sex (men, P(trend) = 0.50; women, P(trend) = 0.16). Findings for other measures (continuous log(25(OH)D), categories of 25(OH)D using sex-/cohort-/season-specific quartiles as cutpoints, categories of season-adjusted residuals of predicted 25(OH)D using quartiles as cutpoints) were generally null, although some measures of increasing 25(OH)D were suggestive of an increased risk for women. Results from stratified analyses and investigations of histologic subtypes of NHL were also null. These findings do not support the hypothesis that elevated circulating 25(OH)D concentration is associated with a reduced risk of NHL. Future research investigating the biologic basis for the sunlight-NHL association should consider alternative mechanisms, such as immunologic effects.

Figure 1.

Forest plots for the meta-analysis of the association between circulating 25-hydroxyvitamin D (25(OH)D) and the risk of non-Hodgkin lymphoma within the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Risk estimates, by cohort, for subjects with circulating 25(OH)D concentrations of <25 nmol/L and ≥100 nmol/L compared with the referent group (50–<75 nmol/L). Results for <25 nmol/L for A) men and B) women; results for ≥100 nmol/L for C) men and D) women. Odds ratios (ORs; boxes) and 95% confidence intervals (CIs; bars) were derived from conditional logistic regression models adjusted for height. The size of each box is inversely proportional to the variance of the log odds ratio estimate in each cohort. The overall estimates (diamonds) were derived from a meta-analysis using random-effects modeling. Data from some cohorts are missing from some forest plots—A): Nurses’ Health Study (NHS), New York University Women's Health Study (NYU-WHS), Shanghai Women's Health Study (SWHS); B): Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC), Health Professionals Follow-up Study (HPFS), Shanghai Men's Health Study (SMHS); C): NHS, NYU-WHS, SWHS; D): ATBC, HPFS, SMHS—because they are sex-specific or have unstable risk estimates due to small numbers. CPS-II, Cancer Prevention Study II Nutrition Cohort; MEC, Multiethnic Cohort Study; PLCO, Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

Figure 1.

Forest plots for the meta-analysis of the association between circulating 25-hydroxyvitamin D (25(OH)D) and the risk of non-Hodgkin lymphoma within the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Risk estimates, by cohort, for subjects with circulating 25(OH)D concentrations of <25 nmol/L and ≥100 nmol/L compared with the referent group (50–<75 nmol/L). Results for <25 nmol/L for A) men and B) women; results for ≥100 nmol/L for C) men and D) women. Odds ratios (ORs; boxes) and 95% confidence intervals (CIs; bars) were derived from conditional logistic regression models adjusted for height. The size of each box is inversely proportional to the variance of the log odds ratio estimate in each cohort. The overall estimates (diamonds) were derived from a meta-analysis using random-effects modeling. Data from some cohorts are missing from some forest plots—A): Nurses’ Health Study (NHS), New York University Women's Health Study (NYU-WHS), Shanghai Women's Health Study (SWHS); B): Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC), Health Professionals Follow-up Study (HPFS), Shanghai Men's Health Study (SMHS); C): NHS, NYU-WHS, SWHS; D): ATBC, HPFS, SMHS—because they are sex-specific or have unstable risk estimates due to small numbers. CPS-II, Cancer Prevention Study II Nutrition Cohort; MEC, Multiethnic Cohort Study; PLCO, Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.