Effect of Interval Between Serum Draw and Follow-up Period on Relative Risk of Cancer Incidence with Respect to 25-hydroxyvitamin D Level: Implications for Meta-analyses and Setting Vitamin D Guidelines

Ecological studies have reported strong inverse correlations between indices of solar ultraviolet-B (UVB) doses and incidence and/or mortality rates for many types of cancer. Case-control studies (CCS) generally find inverse correlations between serum 25-hydroxyvitamin D [25(OH)D] concentration measured at time of diagnosis for cancer incidence, whereas nested case-control studies (NCCS), which involve a several-year follow-up time after serum sampling, generally do not. This paper examines the relation between follow-up interval and relative risk (RR) for breast, colorectal, and prostate cancer. I plot the RR versus serum 25(OH)D data as a function of follow-up time from the literature for each type of cancer. For breast cancer, RRs were significantly reduced only for follow-up periods less than 3 years. For colorectal cancer, RRs were generally significantly reduced for follow-up periods up to 12 years. For prostate cancer, RRs were not statistically significant from 4 years to 28 years. This study included no CCS. Follow-up periods after serum sampling should not be too long for breast cancer because once a tumor reaches a diameter of 1-3 mm, it requires angiogenesis to continue growing, and vitamin D reduces angiogenesis around tumors. Breast cancer diagnoses are more common in spring and fall than in summer or winter, indicating that they can grow rapidly if circulating 25(OH)D drops in the fall or melatonin levels drop in spring. Serum sampling should be conducted during the study, perhaps every 2 years, to overcome the problem of change of 25(OH)D concentration during cohort studies.