Similarities in solar ultraviolet irradiance and other environmental factors may explain much of the family link between uveal melanoma and other cancers

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Sir: The recent paper [1], exploring the family history of cancer for persons diagnosed with uveal melanoma (UM) was aimed at elucidating a hypothesis that there may increased risk for some cancers in carriers of yet unidentified UM predisposition genetic alteration. While that is certainly a hypothesis worthy of further study, it has to be acknowledged that a familial predisposition can also be due to shared environmental factors. Dietary factors play a major role in cancer risk in general [2]. In the case of UM it seems that dietary factors may improve the survival rate [3]. Smoking and alcohol consumption increase cancer risk, and the same has recently been found to be true for a low serum concentration of 25-hydroxyvitamin D [25(OH)D]. Solar ultraviolet-B (UVB) radiation is the primary human source of vitamin D [4], and solar UVB dose has been found to be inversely correlated with risk of uveal melanoma based on an ecological study [5]. Nearly all of the cancers among those diagnosed with UM and their first and second degree relatives listed in Table 3 of Abdel-Rahman[1] are vitamin D sensitive [6–10], possibly with the exception of prostate cancer in terms of incidence [11, 12], although vitamin D status plays a role in survival for this cancer [13]. Still, diet and genetics certainly play important roles in risk for prostate cancer risk [12, 14]. Related to this study [1] are investigations of second cancers for persons diagnosed with non-melanoma skin cancer (NMSC). At latitudes below about 35–40 , NMSC is generally inversely correlated with risk of second cancer [8, 15], while at higher latitudes, NMSC seems to be positively correlated with risk of many types of cancer [15]. This finding was tentatively explained in terms of the skin surface exposed to the sun: At lower latitudes, larger skin surfaces are probably exposed, so that more vitamin D is produced [16]. In addition, diet and smoking are risk factors for both NMSC and many internal cancers, further explaining the correlations at higher latitudes [16]. Thus, any study looking for genetic risk factors for a cancer based on second primary cancers or cancers in first and second degree relatives, should also take into account whether environmental risk factors such as diet, smoking, and solar UVB exposure (producing vitamin D) might, at least partly, explain the links.