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Vitamin D and Cancer<br />
Chapters 3, 4 and 8 summarises the current knowledge on ultraviolet radiation and skin<br />
cancer and the basic biology relevant to this report. Readers interested in more details are invited to<br />
consult the literature cited in these chapters.<br />
Chapter 3 – Sunlight and skin cancer: recall of essential issues<br />
3.1 The skin cancer burden<br />
Increasing incidence of skin cancer starting around the 1950s have been described in all lightskinned<br />
populations, and to some extent, in several Asian and South American populations. These<br />
increases concerned all types of skin cancer, including squamous cell carcinoma (SCC), basal cell<br />
carcinoma (BCC) and cutaneous melanoma. Most recent cancer registry data show that in and after<br />
2004, skin cancer incidence is still rising in nearly all light-skinned populations.<br />
In Denmark, Sweden, and Norway, the incidence of cutaneous melanoma per 100,000 persons<br />
(Age adjusted on World Standard population) rose from below 2 cases per year in the early 1950s to<br />
13 to 15 cases per year in 2005 (Engholm et al.,2008)). In Queensland, Australia, this increase was<br />
from 46 cases in 1982-88 to 67 cases per 100,000 in 2005 (Queensland, 2008).<br />
In many light-skinned populations BCC and SCC combined are the most frequent cancers.<br />
While treatment of BCC and SCC does not require radiotherapy or chemotherapy, surgical and<br />
dermatological management of these cancers in the United States entailed in 1995 an overall direct<br />
cost representing 4.5% of costs associated with management of all cancer sites (Housman et<br />
al.,2003).<br />
In 1992, <strong>IARC</strong> reviewed the epidemiological evidence, evidence from studies with experimental<br />
animals and other relevant data including mechanistic studies and concluded that sun exposure is the<br />
main environmental cause of cutaneous melanoma and of non-melanocytic skin cancer: basal cell<br />
carcinoma (BCC) and squamous cell carcinoma (SCC) (<strong>IARC</strong>, 1992).<br />
3.2 Wavelengths of solar radiation relevant to skin cancer<br />
Optical solar radiation includes UV radiation, visible light and infrared radiation. Wavelengths less<br />
than 290 nm are absorbed by the atmosphere and do not reach the earth’s surface. The Commission<br />
Internationale de l’Eclairage (CIE) divides the UV region into UVC (100 – 280 nm), UVB (280-315 nm)<br />
and UVA (315-400 nm). UVB is stopped by glass and plastic films, and neither sunburn nor<br />
endogenous vitamin D synthesis can be caused by exposure to the sun through a window.<br />
The variation in biological effects (e.g. skin carcinogenesis) by wavelength is referred to as the<br />
action spectrum. The action spectra for sunburn (erythema) (Parrish et al.,1982) and production of<br />
pyrimidine dimers (Freeman et al.,1989) have been determined for human skin. It is not possible from<br />
observational studies of humans exposed to sunlight to determine which wavelengths are primarily<br />
responsible for skin cancer because although the composition of solar radiation varies by latitude,<br />
season, time of day and atmospheric factors, and measuring the exposure to radiation of different<br />
wavelengths and separating their effects is too difficult. Instead, information on the action spectra for<br />
skin cancer has come from experimental studies of laboratory animals.<br />
The albino hairless mouse is a suitable animal model for SCC. Experiments show that for these<br />
mice, the UVB component of sunlight is particularly important for the induction of SCC (de Gruijl et<br />
al.,1993) and that the action spectrum is similar to the action spectrum for erythema (sunburn) for<br />
humans (Parrish et al.,1982).<br />
There are no data on UV action spectrum for BCC and there is no suitable animal model for<br />
melanoma. It was initially thought from a fish model and from a model using that a South American<br />
opossum (Monodelphis domestica), that the action spectrum for melanoma could extend into the<br />
UVA range (Setlow et al.,1993, Ley, 2001). But studies using a new mouse model (hepatocyte growth<br />
factor/scatter factor (HGF/SF) mouse) are consistent with UVB, not UVA, being responsible for<br />
induction of melanoma (De Fabo et al.,2004).<br />
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