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

doi:10.1016/j.jsbmb.2006.12.030

The Journal of Steroid Biochemistry and Molecular Biology

Volume 103, Issues 3–5, March 2007, Pages 668-674

https://doi.org/10.1016/j.jsbmb.2006.12.030 Get rights and content

Abstract

Background

Nearly 20 types of cancer have been found to be inversely correlated with solar ultraviolet-B (UVB) levels determined geographically in ecologic studies, assuming that personal solar UVB irradiances were directly related to July solar UVB doses. This assumption has been questioned.

Methods

Rates of second cancer after diagnosis of nonmelanoma skin cancer (NMSC) from the literature were used in linear regression analyses. The risk modification of NMSC due to smoking was accounted for by comparing second cancer risk ratios (RRs) with lung cancer RRs in regression analysis for each cancer.

Results

For a diagnosis of squamous cell carcinoma, RRs for subsequent colon, gastric, and rectal cancers were significantly reduced, with that for renal cancer being marginally insignificant. For NMSC, RRs for cervical, esophageal, gastric, and rectal cancer were significantly reduced; those for colon and gallbladder cancer were marginally insignificant, while those for female breast, laryngeal, ovarian, renal, and uterine corpus cancers were insignificantly reduced; RRs for lip and salivary gland cancers and melanoma were significantly increased. Melanoma was inversely correlated with lung cancer.

Conclusion

These results provide nearly direct evidence that solar UVB irradiance reduces the risk of many internal cancers. The likely mechanism is production of Vitamin D.

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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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

Abstract

Background

Methods

Results

Conclusion

Introduction

Section snippets

Data and methods

Results

Discussion

Summary and conclusion

Note added in proof

Prev. Med.

J. Steroid Biochem. Mol. Biol.

J. Am. Acad. Dermatol.

J. Invest. Dermatol.

Lung Cancer

J. Am. Acad. Dermatol.

J. Am. Acad. Dermatol.

Ann. Epidemiol.

Prev. Med.

Lancet

An estimate of premature cancer mortality in the United States due to inadequate doses of solar ultraviolet-B radiation

Cancer

The association of solar ultraviolet B (UVB) with reducing risk of cancer: multifactorial ecologic analysis of geographic variation in age-adjusted cancer mortality rates

Anticancer Res.

Do sunlight and Vitamin D reduce the likelihood of colon cancer?

Int. J. Epidemiol.

Sunlight and mortality from breast, ovarian, colon, prostate, and non-melanoma skin cancer: a composite death certificate based case-control study

Occup. Environ. Med.

Ecologic studies of solar UV-B radiation and cancer mortality rates. Recent results

Cancer Res.

Vitamin D3 from sunlight may improve the prognosis of breast-, colon- and prostate cancer (Norway)

Cancer Causes Control

Sun exposure may protect against non-Hodgkin lymphoma: a case-control study

Int. J. Cancer

Ultraviolet radiation exposure and risk of malignant lymphomas

J. Natl. Cancer Inst.

Lower Vitamin D production from solar ultraviolet-B irradiance for black Americans compared to white Americans may explain some of the difference in cancer survival rates

J. Natl. Med. Assoc.

Skin irritation and cancer in the United states Navy

Am. J. Med. Sci.

A critical review of studies on Vitamin D in relation to colorectal cancer

Nutr. Cancer

The role of Vitamin D in cancer prevention

Am. J. Public Health

Vitamin D is associated with improved survival in early stage non-small cell lung cancer patients

Cancer Epidemiol. Biomarkers Prev.

Prospective study of predictors of Vitamin D status and cancer incidence and mortality in men

J. Natl. Cancer Inst.

The causes of skin cancer: a comprehensive review

Drugs Today (Barc.)

Lifestyle differences in twin pairs discordant for basal cell carcinoma of the skin

Br. J. Dermatol.