Geographic variation of prostate cancer mortality rates in the United States: Implications for prostate cancer risk related to vitamin D

Dear Sir, Tuohimaa et al.1 reported that deaths from prostate cancer were more likely at both low and high levels of serum 25(OH)vitamin D3 than at intermediate values, which were relatively low (40–60 nmol/l), indeed lower than the values currently thought necessary to accommodate fully the body’s need for vitamin D to assure proper calcium homeostasis (80 nmol/l). 2 This finding is very interesting and important in that it may provide an explanation for a number of puzzling and inconsistent results from studies investigating the links between prostate cancer, solar UVB radiation (280–315 nm) and vitamin D. While there is considerable observational epidemiologic and in vitro evidence that UVB and/or vitamin D reduce the risk of prostate cancer,1,3,4 there are also a number of reports of no risk reduction with UVB and vitamin D.1 While some of the effect reported by Tuohimaa et al.1 may be due to the negative effects of vitamin A (retinol) found in fish liver oil, which is a major source of vitamin D in Norway,1 this may not explain all of the increased risk of prostate cancer for higher values of 25(OH)vitamin D3. To investigate the matter further, the geographic variation of prostate cancer mortality (PrCM) rates in the United States was analyzed. PrCM rates in the United States do not have the same pattern as rates for other cancers, such as breast, colon, ovarian and rectal cancers, for which UVB and vitamin D are more firmly established as risk-reduction agents.7–10 For such cancers, mortality rates are about twice as high in the northeast as in the southwest and strongly inversely correlated with solar UVB radiation.7,10,11 In addition, 6 types of cancer (breast, colon, endometrial, esophageal, ovarian and non-Hodgkin’s lymphoma) are inversely correlated to both solar UVB radiation and rural residence in combination.11 Urban residence is considered to reduce UVB exposure compared to rural residence in that it does not correlate with any other factor, such as lung cancer. For prostate cancer, the geographic variation is different. For 1970–1994, PrCM was lower in the southeast (14–22 deaths/100,000 yearly) and higher in the northwest (24–28 deaths/100,000 yearly). For 1950–1969, PrCM had a latitudinal dependence, varying from approximately 15 deaths/ 100,000 yearly near 30°N to approximately 23 deaths/100,000 yearly near 45°N. Thus, both the geographic pattern and magnitude of variability are much different for prostate cancer than for the other cancer types. To further investigate the links to geographic variation in PrCM rates in the United States, multiple linear regression analyses were performed for the PrCM rate data for 2 periods, 1970–1994 and 1950–1969, by state for the 48 contiguous states plus the District of Columbia for white males with UVB for July,11 the fraction of the population living in urban regions in 1990 (see Table 44 in U.S. Department of Commerce), the fraction of white Americans with Hispanic heritage in 1995 (see Tables 36 and 37 in U.S. Department of Commerce) and latitude. The results are given in Tables I and II. For the 1970–1994 data, latitude had the highest correlation with PrCM. UVB was weakly correlated, with the second-order correlation being higher than the linear correlation. There was a slight increase at the higher UVB values compared to the intermediate values. Both the fraction living in an urban residence and the fraction of white Americans with Hispanic heritage were weakly inversely correlated with PrCM. There was some confounding for these 2 factors as their adjusted r was 0.32, but this fails both the normality and constant variance tests since some states outside of the southwest, such as New York, have large Hispanic populations. For the 1950–1969 data, latitude again had the highest correlation with PrCM, not counting the almost accidental high inverse correlation for the fraction with Hispanic heritage in the 4-term regression. The second-order regression with UVB again had a higher correlation than the linear regression. These results indicate that adequate wintertime vitamin D could prevent 10,000 cases of prostate cancer and 1,300 premature deaths from prostate cancer in the United States annually. These results are consistent with the results of Tuohimaa et al.1 in that latitude, which may be an inverse proxy for winter/ springtime vitamin D, has a strong correlation with PrCM, suggesting that low vitamin D values are a risk factor for prostate cancer. However, July UVB radiation, an index for summertime vitamin D production, showed a much weaker correlation as well as some increased risk at the higher values, suggesting that high values of vitamin D increase the risk of prostate cancer. The implications of our results and those of Tuohimaa et al.1 include the following. Vitamin D supplementation should be undertaken in wintertime, a period when it is impossible to produce vitamin D by solar UVB exposure in northeastern