Low Plasma 25-Hydroxyvitamin D and Risk of Tobacco-Related Cancer

BACKGROUND: Tobacco smoke chemicals may influence vitamin D metabolism and function, and conversely vitamin D may modify the carcinogenicity of tobacco smoke chemicals. We tested the hypothesis that lower plasma 25-hydroxyvitamin D [25(OH)D] is associated with a higher risk of tobacco-related cancer in the general population. METHODS: A prospective population-based cohort of 9791 individuals from the Copenhagen City Heart Study who were free of cancer at baseline was followed from 1981-1983 until December 2008 with 100% complete follow-up. RESULTS: During up to 28 years of follow-up, 1081 participants developed a tobacco-related cancer and 1506 developed other cancers. Decreasing 25(OH) D concentrations, subdivided by clinical categories or by seasonally adjusted percentile categories, were associated with increasing cumulative incidence of tobacco-related cancer (log-rank trend P = 2 X 10(-6) and P = 5 X 10(-9)). Multivariable adjusted hazard ratios of tobacco-related cancer were 1.75 (95% CI, 1.33-2.30) for 25(OH) D < 5 vs >= 20 ng/mL, and 2.07 (1.63-2.62) for <= 5th vs > 66th percentile. Also, multivariable adjusted hazard ratios for a 50% reduction in 25(OH) D were 1.20 (1.13-1.28) for any tobacco-related cancer, 1.19 (95% CI, 1.09-1.31) for lung cancer, 1.44 (1.19-1.73) for head and neck cancer, 1.28 (1.06-1.54) for bladder cancer, 1.34 (1.04-1.73) for kidney cancer, and 0.95 (0.89-1.01) for other cancers. CONCLUSIONS: Lower plasma 25(OH) D was associated with higher risk of tobacco-related cancers, but not with risk of other cancers. (C) 2013 American Association for Clinical Chemistry