The association between naevi and melanoma in populations with different levels of sun exposure: a joint case-control study of melanoma in the UK and Australia

Abstract

Summary Two case-control studies were set up to investigate the relationship between melanocytic naevi and risk of melanoma and to compare the naevus phenotype in two countries exposed to greatly different levels of sun exposure and different melanoma rates. In England 117 melanoma cases and 163 controls were recruited from the North-East Thames Region and 183 melanoma cases and 162 controls from New South Wales, Australia. Each subject underwent a whole-body naevus count performed by the same examiner in each country. Relative risks associated with melanocytic naevi in each country were calculated with comparison of naevus data in controls between Australia and England. Atypical naevi were strong risk factors for melanoma in both countries: the odds ratio (OR) for three or more atypical naevi was 4.6 (95% Cl 2.0-10.7) in Australia compared with 51.7 (95% Cl 6.5-408.4) in England. Common naevi were also significant risk factors in Australia and England with similar odds ratios in the two countries. Prevalence of atypical naevi was greater in Australian controls than in English controls: OR 9.7 (95% Cl 1.2-81.7) for three or more atypical naevi in Australia compared with England. For young age groups, the median number of common naevi was greater in Australia than in the UK, whereas for older individuals this difference in naevi number between the two countries disappeared. The prevalence of naevi on non-sun-exposed sites in controls was not significantly different between the two countries. The atypical mole syndrome (AMS) phenotype was more prevalent in Australian controls (6%) than in English controls (2%). The results of this study support the role of sun exposure in the induction of atypical naevi in adults. There was a trend towards stronger risk factors associated with atypical naevi in England compared with Australia. The atypical mole syndrome, usually associated with a genetic susceptibility to melanoma, was more common in Australia than in England, suggesting genetic environmental interactions with the possibility of phenocopies induced by sunlight.

Nevus Size and Number Are Associated with Telomere Length and Represent Potential Markers of a Decreased Senescence In vivo

“…Whether longer telomeres also influence other skin phenotypes remains to be determined. However, it has been observed that both the ''moley'' phenotype and the ''sun damage'' phenotype (with solar elastosis and solar keratoses), which are both associated with an increased risk of melanoma, are often mutually exclusive (38,39). It is therefore possible that longer telomere length delays senescence in keratinocytes and fibroblasts so patients with higher nevus counts may display less photoaging.…”

Sun Exposure and the Incidence of Melanocytic Nevi in Young Australian Children

“…In a longitudinal comparison of Scottish and Australian children followed from birth, Australian children experienced a rapid increase in MN counts in their second year of life whereas children raised in the contrasting UVR environment of Scotland showed a delay of f12 months (11). It is interesting to note that there is little difference in the MN counts of older Caucasians from diverse UV environments (7,37,38), despite the consistent differences in melanoma incidence (39,40). These findings suggest that interventions in very young children are necessary to prevent the early onset of MN and melanoma later in life.…”

Ultraviolet Light as a Modulator of Melanoma Development

“…In contrast, melanomas developing on the trunk via the intermittent UVR (non-CSD) pathway tend to have relatively earlier age of onset and are associated with higher naevus count. Several studies have published findings concordant with the divergent pathway hypothesis (Carli and Palli, 2003;Chang et al, 2009;Bataille et al, 1998). Given the strong association between truncal (non-CSD) melanomas and naevus development, and the fact that most naevi carry BRAF mutations (Pollock et al, 2003), it is not surprising that the non-CSD melanomas also tend to carry BRAF mutations (reviewed in .…”