Testing the divergent pathway hypothesis for melanoma: recent findings and future challenges

Whiteman, David C.

doi:10.1586/era.10.42

Cited by 19 publications

(24 citation statements)

References 39 publications

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“…However, melanomas in individuals with low vitamin D (more likely to be older, with skin type 1 or 2 with thicker melanoma tumours) are likely to be quite different from melanomas associated with high naevus counts which affect younger individuals and are associated with thinner melanomas more often of the superficial melanoma type (14). So it is important to separate melanomas associated with high naevus counts from those with low naevus counts as the divergent melanoma pathways in terms of phenotypic risk factors have already been well described (23). High naevus counts whilst increasing melanoma risk, have also been found to offer survival advantage after adjusting for all melanoma prognostic factors (24).…”

Section: Discussionmentioning

confidence: 99%

Positive Association Between Vitamin D Serum Levels and Naevus Counts

Ribero¹,

Glass²,

Mangino³

et al. 2017

Acta Derm Venerol

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Lower vitamin D serum levels are linked to increased melanoma risk and poorer survival. Naevus counts are associated with both melanoma risk and survival and to leucocyte telomere length. Vitamin D is also linked to telomere biology with higher levels of vitamin D in individuals with longer leucocyte telomere length despite adjusting for age. Using the TwinsUK data, we explored the association between naevus count, leucocyte telomere length and vitamin D serum levels. Increasing vitamin D levels were associated with increasing naevus count: serum levels were 73.3 nmol/l in individuals with less than 50 naevi compared to 78.8 nmol/l in individuals with more than 50 naevi (p?=?0.002). In the final regression model, using naevus count as a continuous variable, vitamin D remained associated with higher naevus counts despite adjustment for age, weight, height, season of sampling and twin relatedness (p?=?0.02). Further adjustment for leucocyte telomere length, decreased the magnitude of the association but it remained significant so leucocyte telomere length is not the sole driver of this association. Having large numbers of naevi is associated with higher vitamin D serum levels.

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Section: Discussionmentioning

confidence: 99%

Positive Association Between Vitamin D Serum Levels and Naevus Counts

Ribero¹,

Glass²,

Mangino³

et al. 2017

Acta Derm Venerol

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“…with many nevi), but that larger amounts of sun exposure are needed to drive melanoma development in people with lower proliferative capacity (i.e. with few nevi) [41]. Also in support of our findings are results from one study that observed a significantly stronger association of melanoma with cumulative time outdoors for those who usually develop a deep tan than for those who develop a moderate or no tan [42], and findings from the international Genes, Environment and Melanoma (GEM) Study of significantly stronger associations between recreational sun exposure and multiple melanoma for people with low sun sensitivity than for those with high sun sensitivity, defined by MC1R genotype or pigmentary phenotype [43].…”

Section: Discussionmentioning

confidence: 99%

Early-life sun exposure and risk of melanoma before age 40 years

Cust

Jenkins

Goumas

et al. 2011

Cancer Causes Control

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“…This theory provides a conceptual framework connecting the epidemiologic heterogeneity of melanoma with melanoma risk factors, particularly mole phenotype [30]. Published reports demonstrate that nevogenesis has a strong genetic component [9], [10]; therefore, nevus-prone and nevus-resistant individuals likely have different germline genetic variants that influence their mole phenotypes and melanoma risk.…”

Section: Discussionmentioning

confidence: 99%

Development of a Melanoma Risk Prediction Model Incorporating MC1R Genotype and Indoor Tanning Exposure: Impact of Mole Phenotype on Model Performance

et al. 2014

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BackgroundIdentifying individuals at increased risk for melanoma could potentially improve public health through targeted surveillance and early detection. Studies have separately demonstrated significant associations between melanoma risk, melanocortin receptor (MC1R) polymorphisms, and indoor ultraviolet light (UV) exposure. Existing melanoma risk prediction models do not include these factors; therefore, we investigated their potential to improve the performance of a risk model.MethodsUsing 875 melanoma cases and 765 controls from the population-based Minnesota Skin Health Study we compared the predictive ability of a clinical melanoma risk model (Model A) to an enhanced model (Model F) using receiver operating characteristic (ROC) curves. Model A used self-reported conventional risk factors including mole phenotype categorized as “none”, “few”, “some” or “many” moles. Model F added MC1R genotype and measures of indoor and outdoor UV exposure to Model A. We also assessed the predictive ability of these models in subgroups stratified by mole phenotype (e.g. nevus-resistant (“none” and “few” moles) and nevus-prone (“some” and “many” moles)).ResultsModel A (the reference model) yielded an area under the ROC curve (AUC) of 0.72 (95% CI = 0.69, 0.74). Model F was improved with an AUC = 0.74 (95% CI = 0.71–0.76, p<0.01). We also observed substantial variations in the AUCs of Models A & F when examined in the nevus-prone and nevus-resistant subgroups.ConclusionsThese results demonstrate that adding genotypic information and environmental exposure data can increase the predictive ability of a clinical melanoma risk model, especially among nevus-prone individuals.

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Testing the divergent pathway hypothesis for melanoma: recent findings and future challenges

Cited by 19 publications

References 39 publications

Positive Association Between Vitamin D Serum Levels and Naevus Counts

Positive Association Between Vitamin D Serum Levels and Naevus Counts

Early-life sun exposure and risk of melanoma before age 40 years

Development of a Melanoma Risk Prediction Model Incorporating MC1R Genotype and Indoor Tanning Exposure: Impact of Mole Phenotype on Model Performance

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