Circulating 25-hydroxyvitamin D and risk of lung cancer: a dose-response meta-analysis

Mounting experimental evidence supports a protective effect of high 25-hydroxyvitamin D (25[OH]D), a good indicator of vitamin D status, on risk of various cancers including lung cancer. However, prospective observational studies examining the 25(OH)D-lung cancer association reported inconsistent findings. A dose-response meta-analysis was carried out to elucidate the subject. Potentially eligible studies were identified by searching PubMed and EMBASE databases, and by carefully reviewing the bibliographies of retrieved publications. The summary relative risks (RRs) with 95 % confidence intervals (CIs) were calculated using the random-effects model. Thirteen reports from ten prospective studies were included, totaling 2,227 lung cancer events. Results of the meta-analysis showed a significant 5 % (RR 0.95, 95 % CI 0.91-0.99) reduction in the risk of lung cancer for each 10 nmol/L increment in 25(OH)D concentrations. This inverse association was not significantly modified by area, study duration, sex, methods for 25(OH)D measurement, baseline 25(OH)D levels, or quality score of included studies. There was evidence of a nonlinear relationship between 25(OH)D and risk of lung cancer (p-nonlinearity = 0.02), with the greatest reductions in risk observed at 25(OH)D of nearly 53 nmol/L, and remained protective until approximately 90 nmol/L. Further increases showed no significant association with cancer risk, but scanty data were included in the analyses of high-level 25(OH)D. There was no evidence of publication bias. This dose-response meta-analysis of prospective studies suggests that 25(OH)D may be associated with reduced risk of lung cancer, in particular among subjects with vitamin D deficiencies.