Epidemiological data show an inverse relationship between vitamin D levels and breast cancer incidence. This study investigates the relationship of modeled and measured serum 25-hydroxyvitamin D [25(OH)D] levels with age-standardized incidence rates of breast cancer in 107 countries. The hypothesis being tested is that breast cancer incidence is inversely related to geographically-dependent cutaneous sunlight exposure. A multiple regression approach was used to examine the contributions of ultraviolet B (UVB) irradiance to age-standardized incidence rates of breast cancer in the 107 countries with data on these covariates-total column ozone thickness, per capita intake of alcohol and energy from animal and vegetable sources, cigarettes, proportion of female population overweight, and total fertility. Age-standardized incidence rates were substantially higher at latitudes distant from the equator (R2 = 0.43, p < 0.0001). The dose-response gradient between modeled serum 25(OH)D levels and incidence rates of breast cancer followed a standard inverse dose-response curve. Increasing increments in serum 25(OH)D in the range above 22 ng/mL were associated with incrementally lower incidence rates of breast cancer. According to multiple regression, UVB irradiance adjusted for cloud cover was inversely associated with incidence rates (p = 0.04) after controlling for covariates. Intake of energy from animal sources was also positively associated with incidence rates (p < 0.01). The overall coefficient of determination, R2, was 0.81 (p < 0.0001). There was a protective effect of UVB irradiance on risk of breast cancer that was independent of fertility rate, proportion of the population overweight, alcohol intake, animal energy intake, and other covariates.
