Contents - IARC

Vitamin D and Cancer
young age at onset, and the occurrence of naevi (Whiteman et al.,1998) and many have a mutation in
the BRAF proto-oncogene (Maldonado et al.,2003). In contrast, melanomas occurring on usually sun
exposed sites tend to occur in older age, have a weaker association with the presence of naevi and
are less likely to have BRAF mutations.
Notwithstanding these limitations, the fraction of disease in the population (PAF) attributable to
sun exposure has been estimated at 96% in males and 92% in females in the USA, by comparison of
white and black populations (Armstrong and Kricker, 1993). Comparison of white populations in New
South Wales, Australia, with ethnically similar populations in England and Wales gives a PAF of 89%
(males) and 79% (females) (Armstrong and Kricker, 1993).
3.5 Squamous cell carcinoma (SCC)
The evidence that sun exposure causes SCC is strong. In Australia and the USA, the incidence
of SCC increases with proximity to the equator (Scotto and Fears, 1983, Giles et al.,1988). In the
USA, the relationship with ambient UV measurements is strongest for SCC and weakest for
melanoma (Armstrong and Kricker, 2001). SCCs occur almost exclusively on parts of the body that
are the most heavily exposed to sunlight (Armstrong et al.,1997). Migrants from the United Kingdom to
Australia have a substantially lower risk than native-born Australians and the risk decreases with
increasing age at migration (English et al.,1998). People whose skin is sensitive to sunlight are at
increased risk (IARC, 1992).
Evidence from case-control studies of personal exposure generally shows that the risk increases
directly with total exposure. Armstrong and Kricker (2001) performed a meta-analysis of existing casecontrol
studies; the pooled relative risks comparing the highest versus lowest category of exposure
were 1.53 (1.02–2.27) for total exposure, 1.64 (1.26–2.13) for occupational exposure, 0.91 (0.68–1.22)
for intermittent exposure and 1.23 (0.90–1.69) for a history of sunburn. There is a paucity of wellconducted
epidemiological studies from which a dose-response curve can be estimated with
confidence.
A randomised controlled trial of sunscreen use in Queensland showed a reduced risk for SCC in
the sunscreen group (relative risk = 0.61 (95% CI 0.46-0.81)) (Green et al.,1999). Other randomised
trials have shown that their use can prevent the appearance of new solar keratoses (likely precursors
to SCC) and cause regression in existing solar keratoses (Boyd et al.,1995, Thompson et al.,1993).
Most SCCs show mutations in the tumour suppressor gene tp53 that are consistent with the
effects of sunlight in producing pyrimidine dimers in DNA (Wikonkal and Brash, 1999), and rats and
mice exposed to sunlight or to artificial sources of UV light develop high numbers of SCCs (IARC,
1992).
3.6 Basal cell carcinoma (BCC)
As for SCC, the incidence of BCC increases with proximity to the equator in Australia and the
USA (Scotto and Fears, 1983, Giles et al.,1988). It is most common on anatomic sites usually
exposed to sunlight, but is relatively more common than SCC on occasionally exposed sites
(Armstrong et al.,1997). Migrants from the United Kingdom to Australia have substantially lower risk
than native-born Australians and the risk decreases with increasing age at migration (Kricker et
al.,1991). People whose skin is sensitive to sunlight are at increased risk (IARC, 1992).
Evidence from case-control studies of personal exposure suggests that intermittent exposure is
more important than chronic exposure. Armstrong and Kricker (2001) reported pooled relative risks
comparing the highest versus lowest category of exposure of 0.98 (0.68-1.41) for total exposure, 1.19
(1.07-1.32) for occupational exposure, 1.38 (1.24-1.54) for intermittent exposure and 1.40 (1.29-1.51)
for a history of sunburn. The Queensland randomised trial of sunscreen showed no benefit for BCC
(Green et al.,1999).
Similar mutations in the tumour suppressor gene tp53 to those seen in SCC have been found in
BCC (Ponten et al.,1997).
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