Vitamin D and prostate cancer risk--a less sunny outlook?

Vitamin D insufficiency is an emerging public health concern. National survey data confirm that large proportions of the populations in the United States and Northern Europe have low vitamin D levels (1 , 2). The prevalence of low vitamin D levels looms particularly large among African Americans and others with dark skin (3), the elderly, the overweight (4) and physically inactive, and those with little sun exposure, such as those who live at higher latitudes where sun exposure in the winter does not induce vitamin D formation in skin (5). Interest in vitamin D levels stems from the growing recognition that the low vitamin D levels that are sufficient to avoid rickets, the classical deficiency disease, may be suboptimal for overall health. The associations with low vitamin D range from increases in total mortality (6), cardiovascular disease (7), hypertension (8), and various infectious diseases (7) to poorer bone health (ie, bone fractures and low bone mineral density) (9). Nearly three decades ago, Garland and Garland (10) were among the fi rst to hypothesize a link with cancer, specifi cally suggesting that inadequate vitamin D levels could represent an important risk factor for colorectal cancer. Since that time, an increasing spate of studies have emerged suggesting links between poor vitamin D status and cancer incidence and mortality, particularly for digestive cancers (11). For example, using prospectively collected samples in a nested case – control design, the risk of colon cancer among individuals with the lowest vitamin D levels were about two times higher than those with the highest intake among both men and women (12). Epidemiological evidence also points to a role of inadequate vitamin D status and risk of cancers of the breast and pancreas (12). Findings for vitamin D and prostate cancer have been less consistent (12). Most studies have reported null associations (13 , 14); some have reported inverse associations in subgroups defi ned by tumor characteristics or by genetic variants (15), but these subgroup fi ndings have not been consistent. The setting of research on risk factors for prostate cancer — that is, widespread prostate-specifi c antigen (PSA) screening and considerable biologic hetero-geneity of the disease — poses several diffi culties for contemporary epidemiology. The prevalence of prostate cancer among middle-aged and older men is high, to the extent that half of US men over age 60 likely harbor a prostate cancer, although many of the tumors …