Contents - IARC

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