Nonoptimal Follow-up Times Make It Difficult to Detect the Epidemiological Inverse Relationship Between 25-Hydroxyvitamin D and Lung Cancer

Background: Previous studies have reported controversial conclusions regarding the association between circulating 25-hydroxyvitamin D (25-HVD) and lung cancer risk. Objectives: To test the hypothesis that the controversial conclusions can be due to different follow-up times (FUT) and because of interpreting findings predominantly based on statistical significance. Methods: The Kuopio Ischaemic Heart Disease Risk Factor Study provided data. We used the Cox regression to study the association between 25-HVD and lung cancer risk in 2578 middle-aged Finnish men. Out of them, 808 were free of cancer and willing to participate in follow-up examinations 11 years after baseline. We repeated all analyses for them. Results: Higher circulating 25-HVD predicted lower lung cancer risk over the entire follow-up period of 33 years. The hazard ratio (HR) of the highest vs. the lowest 25-HVD tertile adjusted for age, smoking, alcohol consumption, body weight status, inflammatory status, physical activity, and diet was lowest, 0.39 (95% CI: 0.17-0.87), when the FUT was 15 years. The HR was statistically significant (p < 0.05) only when the FUT was 15-17 years. In the sub-cohort, Cohen's d denoted a large or medium effect during the first 11 years. Conclusions: The optimal FUT in this prospective cohort study investigating the association between circulating 25-HVD and lung cancer risk in a middle-aged male population, 50-55 years, was 15 years. When the population aged for 11 years, shorter FUTs became more pertinent. In general, interpreting results of prospective cohort studies with respect to FUTs and effect sizes may lead to more precise conclusions. Moreover, researchers should consider FUTs when they combine studies meta-analytically.