The Journal of Steroid Biochemistry and Molecular Biology
A meta-analysis of second cancers after a diagnosis of nonmelanoma skin cancer: Additional evidence that solar ultraviolet-B irradiance reduces the risk of internal cancers
Introduction
Solar ultraviolet-B (UVB; 290–315 nm) irradiance has been found to be inversely correlated with nearly 20 types of cancer in several observational studies [1], [2]. The strongest evidence is for breast, colon, lung, and ovarian cancer, for which most of the studies are observational, generally ecologic in nature [3], [4], [5], [6], [7], [8], [9], [10]. The hypothesis for the link between solar UVB irradiance and reduction of cancer risk is photoproduction of Vitamin D [3]. Evidence for this hypothesis extends back to 1937 [11]. Dietary Vitamin D and serum 25-hydroxyvitamin D [25(OH)D] studies support this link when sufficient levels of either are considered [12], [13], [14]. Case-control [15] and cohort [16] studies based on a Vitamin D index also support this hypothesis. However, since these studies are observational in nature, being primarily ecologic studies in which personal UVB irradiance was not determined, some other factors could explain the largely latitudinal or seasonal variations in cancer incidence and mortality rates.
Thus, a more direct measure of personal solar UVB irradiance is needed. To further investigate the links between solar UVB irradiance and risk of cancer, a meta-analysis of studies of second cancers following diagnosis of skin cancer of squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and nonmelanoma skin cancer (NMSC) was performed. UV irradiance is an important risk factor for skin cancer [17], so the population of those who developed either form of skin cancer can be generally assumed to have experienced greater UV irradiance than did the general population.
However, other factors also contribute to skin cancer risk. At the population level, smoking is perhaps the most important. Smoking has been linked to risk of BCC [18], [19] and SCC [20], [21], [22]. The likely mechanism is reduction in antioxidant defenses since smoking generates free radicals leading to skin aging [23], and skin cancer is due largely to free radicals [24]. Smoking is also an important risk factor for many types of cancer [25]. Thus, this meta-analysis should have included consideration of the prevalence of smoking among each population as well as the history of skin cancer; however, such data are generally unavailable and unreliable, since they could not extend far enough back in time to be complete?
The analysis described here thus seeks to determine whether personal UV irradiance history as determined by skin cancer incidence, corrected for estimated smoking levels by each population, can be used as further evidence that solar UVB irradiance reduces the risk for several internal cancers.
Section snippets
Data and methods
All papers reporting second cancers after development of BCC and/or SCC skin cancer were found through the reference list in Nugent et al. [26] and by further search of the National Library of Medicine's PubMed database [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40]. Characteristics of the studies are presented in Table 1, Table 2. Studies with fewer than 800 skin cancer cases were omitted. Earlier studies that were replaced by later studies, such as in
Results
The results are given in Table 3, Table 4. Some results for cancers of the female organs are given for males and females combined because some studies combined the two sexes and because the lung cancer RRs were for males and females combined.
For SCC, the RRs for colon, gastric, and rectal cancers were found to be significantly reduced for males and females combined, with the RR for renal cancer being marginally insignificant. The RRs for melanoma and mouth cancer were found to be significantly
Discussion
These results indicate that cancer RRs are often significantly reduced for those having a diagnosis of skin cancer prior to diagnosis of a second cancer when smoking history is taken into account. For some of the less common cancers, a significant risk reduction was not found, since the numbers of cases were often low.
Melanoma is, of course, linked to UV irradiance, especially UVA [42], but not to smoking. Vitamin D and UVB reduce the risk of melanoma [43], [44], [45]. However, due to the
Summary and conclusion
These results provide strong support for the finding in many ecologic and other observational studies that solar UVB, through production of Vitamin D, is an important risk reduction factor for cancer incidence and mortality and increased survival rates since these results are limited to those people in the populations who are very likely to have experienced greater lifetime solar UV irradiance.
A recent study found that the economic burden of foregone benefits of solar UVB irradiance and Vitamin
Note added in proof
The results presented in this paper were used in an ecologic study of cancer mortality rates in Spain. It was found that NMSC mortality rates were inversely correlated with 17 types of cancer including melanoma [53]. This index appeared to be better than latitude, probably in part because UVB irradiances are higher in some provinces due to higher fractions of the population having outdoor occupations, and in part because there is a strong latitudinal gradient in socioeconomic status that
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