Background Melanoma risk prediction models could be useful for matching preventive interventions to patients' risk.Objectives To develop and validate a model for incident first-primary cutaneous melanoma using clinically assessed risk factors. Methods We used unconditional logistic regression with backward selection from the Australian Melanoma Family Study (461 cases and 329 controls) in which age, sex and city of recruitment were kept in each step, and we externally validated it using the Leeds Melanoma Case-Control Study (960 cases and 513 controls). Candidate predictors included clinically assessed whole-body naevi and solar lentigines, and self-assessed pigmentation phenotype, sun exposure, family history and history of keratinocyte cancer. We evaluated the predictive strength and discrimination of the model risk factors using odds per age-and sex-adjusted SD (OPERA) and the area under curve (AUC), and calibration using the Hosmer-Lemeshow test. Results The final model included the number of naevi ≥ 2 mm in diameter on the whole body, solar lentigines on the upper back (a six-level scale), hair colour at age 18 years and personal history of keratinocyte cancer. Naevi was the strongest risk factor; the OPERA was 3Á51 [95% confidence interval (CI) 2Á71-4Á54] in the Australian study and 2Á56 (95% CI 2Á23-2Á95) in the Leeds study. The AUC was 0Á79 (95% CI 0Á76-0Á83) in the Australian study and 0Á73 (95% CI 0Á70-0Á75) in the Leeds study. The Hosmer-Lemeshow test P-value was 0Á30 in the Australian study and < 0Á001 in the Leeds study. Conclusions This model had good discrimination and could be used by clinicians to stratify patients by melanoma risk for the targeting of preventive interventions.

Background: People at high risk of developing melanoma are usually identified by pigmentary and naevus phenotypes. Objective: We examined whether associations of these phenotypes with melanoma risk differed by ambient sun exposure or participant characteristics in two population-based, case-control studies with comparable ancestry but different ambient sun exposure. Methods: Data were analysed from 616 cases and 496 controls from the Australian Melanoma Family Study and 2,012 cases and 504 controls from the Leeds (UK) case-control study. Questionnaire, interview and dermatological skin examination data were collected using the same measurement protocols. Relative risks were estimated as odds ratios using unconditional logistic regression, adjusted for potential confounders. Results: Hair and skin colour were the strongest pigmentary phenotype risk factors. All associations of pigmentary phenotype with melanoma risk were similar across countries. The median number of clinically assessed naevi was approximately three times higher in Australia than Leeds, but the relative risks for melanoma associated with each additional common or dysplastic naevus was higher for Leeds than Australia, especially for naevi on the upper and lower limbs. Higher naevus counts on the head and neck were associated with a stronger relative risk for melanoma for women than men. The two countries had similar relative risks for melanoma based on self-reported naevus density categories, but personal perceptions of naevus number differed by country. There was no consistent evidence of interactions between phenotypes on risk. Conclusions: Classifying people at high risk of melanoma based on their number of naevi should ideally take into account their country of residence, type of counts (clinical or self-reported), body site on which the naevus counts are measured, and sex. The presence of naevi may be a stronger indicator of a genetic predisposition in the UK than in Australia based on less opportunity for sun exposure to influence naevus development.

Summary Background Several preclinical studies have identified the antiproliferative effects of 25‐hydroxyvitamin D [25(OH)D; vitamin D]. Ultraviolet radiation (UVR) is essential for vitamin D synthesis yet increases the risk of melanoma. Observational studies on the association of vitamin D levels with melanoma risk have reported inconclusive results, and are difficult to interpret owing to the potential confounding from the dual role of UVR. Objectives To determine whether there is a causal association between genetically predicted 25(OH)D concentrations and melanoma using a Mendelian randomization (MR) approach. Methods We performed MR using summary data from a large genome‐wide association study (GWAS) meta‐analysis of melanoma risk, consisting of 12 874 cases and 23 203 controls. Five single nucleotide polymorphisms associated with 25(OH)D concentration – rs12785878, rs10741657, rs2282679, rs6013897 and rs116970203 – were selected as instrumental variables. An inverse variance weighted method was used to access the evidence for causality. MR results from the melanoma meta‐analysis were combined with results from an MR study based on a melanoma risk GWAS using UK Biobank data. Results A 20 nmol L−1 decrease in 25(OH)D was not associated with melanoma risk [odds ratio (OR) 1·06, 95% confidence interval (CI) 0·95–1·19]. Results from the UK Biobank were concordant with this, with meta‐analysis of our and UK Biobank‐derived MR causal estimates showing no association (OR 1·02, 95% CI 0·92–1·13 for a 20 nmol L−1 decrease). Conclusions The results suggest that vitamin D levels may not be causally associated with the risk of melanoma. What's already known about this topic? Antitumour activity of vitamin D has been identified in preclinical studies. Observational studies link vitamin D deficiency with an increased risk of a range of cancers. There is a growing public interest for vitamin D supplementation. Observational studies of melanoma are fraught with difficulties because while higher ultraviolet radiation levels increase vitamin D levels, such exposure is also associated with increased melanoma risk. Results from observational studies are inconclusive regarding the effect of vitamin D on melanoma risk. What does this study add? Using Mendelian randomization, an approach to causal inference, which is analogous to a natural randomized controlled trial, we found no causal association between vitamin D levels and melanoma.

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Summary To examine the role of ethnic origin as a risk factor for paediatric lymphoma, a cancer registrybased analysis was undertaken in Yorkshire, UK. Children of Asian ethnic origin were found to have an odds ratio for lymphomas of 1.60 (CI 0.98-2.62), after adjusting for age and sex. After adjusting also for 'super profile group' as an indicator of socioeconomic status, the estimate became 1.99