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Background: We report the development of a cutaneous melanoma risk algorithm based upon seven factors; hair color, skin type, family history, freckling, nevus count, number of large nevi, and history of sunburn, intended to form the basis of a self-assessment Web tool for the general public., Methods: Predicted odds of melanoma were estimated by analyzing a pooled dataset from 16 case-control studies using logistic random coefficients models. Risk categories were defined based on the distribution of the predicted odds in the controls from these studies. Imputation was used to estimate missing data in the pooled datasets. The 30th, 60th, and 90th centiles were used to distribute individuals into four risk groups for their age, sex, and geographic location. Cross-validation was used to test the robustness of the thresholds for each group by leaving out each study one by one. Performance of the model was assessed in an independent UK case-control study dataset., Results: Cross-validation confirmed the robustness of the threshold estimates. Cases and controls were well discriminated in the independent dataset [area under the curve, 0.75; 95% confidence interval (CI), 0.73-0.78]. Twenty-nine percent of cases were in the highest risk group compared with 7% of controls, and 43% of controls were in the lowest risk group compared with 13% of cases., Conclusion: We have identified a composite score representing an estimate of relative risk and successfully validated this score in an independent dataset., Impact: This score may be a useful tool to inform members of the public about their melanoma risk., (©2015 American Association for Cancer Research.)

Background: Current staging algorithms in melanoma patients undergoing therapeutic lymph node dissection (LND) fail to accurately distinguish long-term survivors from those at risk of rapid relapse. Our goal was to establish and validate nomograms for predicting both recurrence and survival after LND., Methods: A prospective cohort of stage IIIB and IIIC melanoma patients was ascertained from a tertiary hospital in Brisbane, Australia. Failure-time multivariate analysis identified key factors that, in adjusted combinations, generated nomograms to predict 2-year recurrence and 5-year melanoma-specific survival. The predictive value of these nomograms was further validated in a patient cohort from Rotterdam, The Netherlands., Results: In 494 Australian patients, number of positive lymph nodes, extra-capsular extension and nodular histopathological subtype were the main independent predictors of 2-year recurrence while age, number of positive nodes and extra-capsular extension were the independent predictors of survival. Predictive value was confirmed in The Netherlands cohort of 331 patients. The nomograms were able to classify patients according to their 2-year recurrence and 5-year survival rates even within each stage III sub-class., Conclusions: Models that include extra-capsular extension predict outcomes in patients with clinically involved lymph nodes. This tool may help tailor treatment and monitoring of this group of patients., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The objective of this study was to investigate the risk factors for melanoma on the arms and legs in comparison with well-known risk factors for trunk melanoma. The study was a population-based case-control study of 77 individuals with limb (25 arm; 52 leg) and 86 with trunk melanoma, who were representative of all the individuals newly-diagnosed with primary limb melanomas in Queensland during 1979-1980 and 232 controls. A single physician interviewed and examined all individuals and assessed complexion type, sun exposure history and other potential risk factors and clinical features. After multivariate analysis, the strongest risk factor for both limb and trunk melanomas was the presence of more than 10 naevi on the arm (odds ratio limb melanoma=41.4, 95% confidence interval 10.4-164), though on histology, a preexisting naevus was more strongly associated with trunk than limb melanoma (P<0.004). Associations with blonde/light brown hair, propensity to freckle and sunburn were similar for melanoma on both sites. A lifetime history of painful sunburns significantly raised the risk of trunk but not limb melanoma, whereas solar keratoses on the arm or face were more strongly associated with limb than with trunk melanoma (marginally significant, P(homogeneity)=0.056). High ambient solar ultraviolet radiation in adolescence was also a stronger risk factor for limb than for trunk melanoma. In conclusion, this population-based investigation into specific differences in causes of limb versus melanomas of other sites suggests that the risk factor profile is intermediate between the profiles for head/neck melanoma (mostly cumulative sun damage) and for trunk melanomas (most strongly related to naevi).

Objective: To investigate risk factors for lentigo maligna melanoma (LMM) compared with superficial spreading melanoma (SSM)., Design: Population-based case-control study in Queensland, Australia., Setting: General community., Participants: Population-based sample of 49 patients with LMM and 141 with SSM (in situ or invasive) aged 14 to 86 years at diagnosis in 1979 and 1980 and 232 control subjects. Response rates were 97.1% in cases and 91.8% in controls., Main Outcome Measures: Risks of both subtypes in relation to phenotypic and environmental factors, estimated by multinomial logistic regression., Results: The number of solar lentigines was the strongest determinant for LMM (odds ratio [OR], 15.93; P < .001 for trend) and significantly weaker for SSM (4.61; P < .001 for trend; P = .04 for homogeneity). Skin cancer history was significantly associated with LMM (OR, 2.84) but not with SSM (1.33; P = .07 for homogeneity). In contrast, the number of nevi was the strongest determinant for SSM (OR, 23.22; P < .001 for trend) while significantly weaker for LMM (3.60; P = .02 for trend; P < .001 for homogeneity). Multiple lifetime sunburns almost tripled the risk for SSM, whereas no association was detected with LMM (P = .04 for homogeneity). Shared risk factors for both subtypes were the number of solar keratoses (P < .001 for trend for both) and sun-sensitive complexion (ie, light eye/hair colors, sunburn propensity, and freckling) (2-fold to 5-fold increased risks)., Conclusions: A propensity to lentigines is a stronger predictor of LMM, whereas high nevus propensity is a stronger predictor of SSM. Skin cancer history appears to determine LMM risk only, whereas the number of lifetime sunburns determines SSM only. Prevention strategies could be tailored differently given these distinctive points of difference.

Introduction: Dermoscopic understanding of naevus characteristics is essential baseline knowledge for identifying early malignant changes., Method: This cross-sectional study includes 34 patients (56% female, mean age 48 years) at high risk of melanoma (personal or a first degree family member with history of melanoma) and 31 moderate/low melanoma risk volunteers (55% female, mean age 37 years) recruited at the Princess Alexandra Hospital, Brisbane, between October 2009 and March 2010. Participants received full body and individual dermoscopic imaging of clinically significant naevi (≥2 mm on the back of male/female and lower limbs of female and ≥5 mm at other body sites). Dermoscopic patterns of naevi were compared between people at high versus moderate/low melanoma risk according to age and body site., Results: In both high and moderate/low risk groups, globular naevi predominated on the head/neck and abdomen/chest, reticular and non-specific naevi on the back, and non-specific pattern on the upper and lower limbs. Non-specific naevi were the most common in all age groups. In both risk groups, globular naevi were more frequent in the younger age bracket, and reticular naevi were more frequent in the older age bracket. Mixed naevus patterns were infrequent and were more common in the younger age brackets of both risk groups., Conclusion: Our preliminary data shows that dermoscopic naevus patterns were similar for age and body site in people at different levels of melanoma risk, suggesting high melanoma risk does not influence dermoscopic naevus patterns., (© 2011 The Authors; Australasian Journal of Dermatology © 2011 The Australasian College of Dermatologists.)

Although risk factors for primary cutaneous melanoma are well defined, relatively little is known about predictors for second primary melanoma. Given the rising incidence of this cancer, coupled with improvements in survival, there is a prevalent and growing pool of patients at risk of second primary melanomas. To identify the predictors of second primary melanoma, we followed a cohort of 1,083 Queensland patients diagnosed with incident melanoma between 1982 and 1990 and who completed a baseline questionnaire. During a median follow-up of 16.5 years, 221 patients were diagnosed with at least one additional primary melanoma. In multivariate analyses, second primary melanomas were associated with high nevus count (hazard ratio (HR), 2.91; 95% confidence interval (CI) 1.94-4.35), high familial melanoma risk (HR, 2.12; 95% CI 1.34-3.36), fair skin (HR, 1.51; 95% CI 1.06-2.16), inability to tan (HR, 1.66; 95% CI 1.13-2.43), an in situ first primary melanoma (HR, 1.36; 95% CI 0.99-1.87), and male sex (HR, 1.49; 95% CI 1.12-2.00). Patients whose first primary was lentigo maligna melanoma (HR, 1.80; 95% CI 1.05-3.07) or nodular melanoma (HR, 2.13; 95% CI 1.21-3.74) had higher risks of subsequent primaries than patients whose first primary tumor was superficial spreading melanoma. These characteristics could be assessed in patients presenting with first primary melanoma to evaluate risk of developing a second primary.

Background: Melanoma risk is related to sun exposure; we have investigated risk variation by tumour site and latitude., Methods: We performed a pooled analysis of 15 case-control studies (5700 melanoma cases and 7216 controls), correlating patterns of sun exposure, sunburn and solar keratoses (three studies) with melanoma risk. Pooled odds ratios (pORs) and 95% Bayesian confidence intervals (CIs) were estimated using Bayesian unconditional polytomous logistic random-coefficients models., Results: Recreational sun exposure was a risk factor for melanoma on the trunk (pOR = 1.7; 95% CI: 1.4-2.2) and limbs (pOR = 1.4; 95% CI: 1.1-1.7), but not head and neck (pOR = 1.1; 95% CI: 0.8-1.4), across latitudes. Occupational sun exposure was associated with risk of melanoma on the head and neck at low latitudes (pOR = 1.7; 95% CI: 1.0-3.0). Total sun exposure was associated with increased risk of melanoma on the limbs at low latitudes (pOR = 1.5; 95% CI: 1.0-2.2), but not at other body sites or other latitudes. The pORs for sunburn in childhood were 1.5 (95% CI: 1.3-1.7), 1.5 (95% CI: 1.3-1.7) and 1.4 (95% CI: 1.1-1.7) for melanoma on the trunk, limbs, and head and neck, respectively, showing little variation across latitudes. The presence of head and neck solar keratoses was associated with increased risk of melanoma on the head and neck (pOR = 4.0; 95% CI: 1.7-9.1) and limbs (pOR = 4.0; 95% CI: 1.9-8.4)., Conclusion: Melanoma risk at different body sites is associated with different amounts and patterns of sun exposure. Recreational sun exposure and sunburn are strong predictors of melanoma at all latitudes, whereas measures of occupational and total sun exposure appear to predict melanoma predominately at low latitudes.

An abnormal nevus phenotype is associated with an increased risk of melanoma. We report a pooled analysis conducted using individual nevus data from 15 case-control studies (5,421 melanoma cases and 6,966 controls). The aims were to quantify the risk better and to determine whether relative risk is varied by latitude. Bayesian unconditional logistic random coefficients models were employed to study the risk associated with nevus characteristics. Participants with whole body nevus counts in the highest of 4 population-based categories had a greatly increased risk of melanoma compared with those in the lowest category (pooled odds ratio (pOR) 6.9 (95% confidence interval (CI): 4.4, 11.2) for those aged<50 years and pOR 5.1 (95% CI: 3.6, 7.5) for those aged>or=50). The pOR for presence compared with absence of any clinically atypical nevi was 4.0 (95% CI: 2.8, 5.8). The pORs for 1-2 and >or=3 large nevi on the body compared with none were 2.9 (95% CI: 1.9, 4.3) and 7.1 (95% CI: 4.7, 11.6), respectively. The relative heterogeneities among studies were small for most measures of nevus phenotype, except for the analysis of nevus counts on the arms, which may have been due to methodological differences among studies. The pooled analysis also suggested that an abnormal nevus phenotype is associated most with melanomas on intermittently sun-exposed sites. The presence of increased numbers of nevi, large nevi and clinically atypical nevi on the body are robust risk factors for melanoma showing little variation in relative risk among studies performed at different latitudes., (Copyright (c) 2008 Wiley-Liss, Inc.)

We compared trends in melanoma incidence by body site in two populations exposed to different levels of sunlight and different approaches to melanoma prevention. We analysed site-specific melanoma incidence during the period 1982-2001 in Queensland, Australia (n=28 862 invasive melanomas; 2536 lentigo maligna melanomas) and the west of Scotland (n=4278 invasive melanomas; 525 lentigo maligna melanomas). Analyses were stratified by sex and age group (<40 years, 40-59 years, >/=60 years). We estimated annual percentage change (APC) in melanoma incidence by regressing the logarithms of the rates and exponentiating the coefficients. Among men, overall melanoma incidence increased log-linearly in both settings, but significantly more rapidly in the west of Scotland (APC 2.8%) than Queensland (APC 1.4%). Rates of increase among Scottish men were higher for every body site and all ages than among Queensland men. Among women, overall melanoma incidence increased more rapidly among Scottish (APC 1.8%) than Queensland women (APC 0.7%). Most discrepant were trends in upper limb melanomas, which underwent large annual increases among Scottish women, but declined among younger Queensland women. Melanoma incidence continues to rise rapidly in all age groups in Scotland and among older people in Queensland. Rates of melanoma in younger people in Queensland are stabilizing, as might be expected if primary prevention campaigns were effective in reducing solar exposure. Variations in rates of change at different body sites warrant further monitoring.

Cutaneous malignant melanoma (CMM) is a major health issue in Queensland, Australia, which has the world's highest incidence. Recent molecular and epidemiologic studies suggest that CMM arises through multiple etiological pathways involving gene-environment interactions. Understanding the potential mechanisms leading to CMM requires larger studies than those previously conducted. This article describes the design and baseline characteristics of Q-MEGA, the Queensland Study of Melanoma: Environmental and Genetic Associations, which followed up 4 population-based samples of CMM patients in Queensland, including children, adolescents, men aged over 50, and a large sample of adult cases and their families, including twins. Q-MEGA aims to investigate the roles of genetic and environmental factors, and their interaction, in the etiology of melanoma. Three thousand, four hundred and seventy-one participants took part in the follow-up study and were administered a computer-assisted telephone interview in 2002-2005. Updated data on environmental and phenotypic risk factors, and 2777 blood samples were collected from interviewed participants as well as a subset of relatives. This study provides a large and well-described population-based sample of CMM cases with follow-up data. Characteristics of the cases and repeatability of sun exposure and phenotype measures between the baseline and the follow-up surveys, from 6 to 17 years later, are also described.

To explore whether the anatomic distribution of melanoma differs with ambient sunlight levels, we compared age- and site-specific melanoma incidence in two genetically similar populations from different geographic regions. We ascertained all new cases of invasive cutaneous melanoma in the west of Scotland and Queensland 1982-2001. Melanoma incidence was calculated for four anatomic regions (head and neck, trunk, upper and lower limbs), standardized to the European population and adjusted for relative surface area of each site. Highest rates among males aged <40 years and 40-59 years were observed on the trunk, but on the upper limbs among Queensland females and lower limbs among Scottish females. After age 60, melanoma rates were highest on the head and neck in both sexes. In both sexes and at all ages, lower limb melanomas were more common in Scotland than expected from the Queensland population. These analyses indicate that while the overall distribution of melanoma is similar in populations with different levels of ambient sunlight, important differences remain. Identifying the causes of these differences is likely to provide better understanding of how sunlight causes melanoma.

Objective: Emerging evidence suggests that melanomas arising on the head and neck that are not lentigo maligna melanomas have different associations with phenotypic and environmental risk factors than those on the trunk and other sites. We sought to test this hypothesis in a population-based study in Queensland, Australia., Methods: Risk factor data were collected from 2360 participants with incident cutaneous melanoma diagnosed 1982--1990, including 167 participants with lentigo maligna melanoma. For each risk factor, polytomous logistic regression analysis, using the trunk as a reference category, was used to estimate the odds ratio and 95% confidence interval for cutaneous melanomas by anatomical site., Results: Participants with melanomas of the head and neck were significantly older than those with melanomas of the trunk (males 52.7 versus 49.7 years; females 47.8 versus 40.5 years). Compared with patients with truncal melanomas, those of the head and neck were less likely to have many nevi (OR 0.41, 95% CI 0.13--1.31), although this did not reach statistical significance. Among females, melanomas of the lower limb were negatively associated with a past history of non-melanoma skin cancer (OR 0.41, 95% CI 0.23-0.74)., Conclusions: We have observed heterogeneity for melanoma risk by anatomical site, lending weight to the hypothesis that cutaneous melanomas may develop through multiple causal pathways.

Background: Although melanocytic nevi are the strongest known risk factors for melanoma, their etiology is not well understood., Objectives: This study was performed to assess the roles of constitutional pigmentary factors and sun exposure in the development of new nevi in adolescents., Methods: A cohort of 111 school children, aged 12 and 13 years at baseline, were followed up for 5 years. Whole-body counts of nevi of all sizes and detailed sun exposure histories were updated each year. Analyses of full-body nevus counts and of nevus counts on the face and neck region and on the shoulder and back region were undertaken by means of log-linear regression, allowing for repeated measures., Results: Mean whole-body nevus counts were 130.1 (SD = 69.9) in 1990 and 215.5 (SD = 127.1) in 1994. Shoulder and back counts were consistently higher than face and neck counts. Subjects with heavy shoulder freckling had increased nevus counts on all sites investigated, with a means ratio for whole-body counts of 1.11 (95% CI, 1.03-1.19), compared with those with no freckling. Those who spent all of their school lunch times in the midday sun had a means ratio of 1.62 (95% CI, 1.15-2.29) compared with those who spent very little time in the sun during the lunch period. Summer holiday sun exposure was not significantly associated with development of nevi in this adolescent cohort., Conclusion: The degree of freckling, especially on the shoulders, and habitual midday sun exposure, rather than holiday sun exposure, are significant determinants of melanocytic nevi in Queensland adolescents.

All melanocytic nevi on the faces and necks of a cohort of students, initially aged 12-14 y, were mapped and photographed annually for 4 y. The features of each nevus were charted yearly noting changes in size and profile, and the appearance or disappearance of any nevi on a student's face and neck was recorded. Nevi were classified by size (small, < 2 mm; medium, 2-5 mm; large, > 5 mm), and by profile (flat, raised). Data from 20 adolescents selected randomly from the cohort for detailed analysis showed males had about twice as many nevi as females, but there was little difference between sexes in their patterns of nevus development. Approximately half the nevi were small in all years; under 5% were large. Over the 4 y of follow-up the proportion of flat nevi dropped from 70% to 57%, whereas nevus numbers increased by 47% in year 1, with smaller increases in older students. Most new or disappearing nevi were small and flat, although both incident and disappearing nevi could be larger and/or raised. Of the existing nevi that altered in the follow-up period, the tendency was towards an increase in size among raised but not among flat nevi; a lowering of profile among small nevi; and a raising of profile among larger nevi; but there were many exceptions to this pattern. Among several host factors examined, inability to tan after sun exposure was found to be significantly negatively associated with the propensity of nevi to change size over the study period. Overall our findings indicate that, contrary to conventional belief, there is a measurable turnover among melanocytic nevi even in early life.

Sun exposure is the main environmental risk factor for melanoma, but the timing of exposure during life that confers increased risk is controversial. Here we provide the first report of the association between lifetime and age-specific cumulative ultraviolet exposure and cutaneous melanoma in Queensland, Australia, an area of high solar radiation, and examine the association separately for families at high, intermediate and low familial melanoma risk. Subjects were a population-based sample of melanoma cases diagnosed and registered in Queensland between 1982 and 1990 and their relatives. The analysis included 1,263 cases and relatives with confirmed cutaneous melanoma and 3,111 first-degree relatives without melanoma as controls. Data on lifetime residence and sun exposure, family history and other melanoma risk factors were collected by a mailed questionnaire. Using conditional multiple logistic regression with stratification by family, cumulative sun exposure in childhood and in adulthood after age 20 was significantly associated with melanoma, with estimated relative risks of 1.15 per 5,000 minimal erythemal doses (MEDs) from age 5 to 12 years, and 1.52 per 5 MEDs/day from age 20. There was no association with sun exposure in families at high familial melanoma risk. History of nonmelanoma skin cancer (relative risk [RR] = 1.26) and multiple sunburns (RR = 1.31) were significant risk factors. These findings indicate that sun exposure in childhood and in adulthood are important determinants of melanoma but not in those rare families with high melanoma susceptibility, in which genetic factors are likely to be more important., (Copyright 2002 Wiley-Liss, Inc.)

A long-term retrospective follow-up study was performed to evaluate the risk of skin cancer in 1098 renal transplant recipients in Queensland, Australia. In a subgroup, we also assessed the influence of immunosuppressive therapy on the risk of developing skin cancer: cyclosporine alone or in combination with prednisolone; azathioprine alone or in combination with prednisolone; or the combination of cyclosporine and azathioprine with or without prednisolone. The cumulative incidence of developing skin cancer, calculated by life table analysis, increased progressively from 7% after 1 year of immunosuppression to 45% after 11 years and to 70% after 20 years of immunosuppression. Multivariate analysis in a subgroup comparing the risk of developing skin cancer in patients on either long-term cyclosporine or azathioprine (each with or without prednisolone) and in patients on the combination of cyclosporine and azathioprine (with or with- out prednisolone) showed no differences between the groups. We conclude that it is likely that the increased risk of skin cancer associated with immunosuppression is independent of the agent(s) used and is a result of the immunosuppression per se.

This population-based case-control study contrasted nutrient intakes of 41 women with cutaneous malignant melanoma to those of 297 women sampled from the same community (Brisbane, Australia). Diet was assessed by a comprehensive food frequency questionnaire. The strong inverse relation we observed between high intakes of polyunsaturated fatty acids and melanoma (P < 0.01) adds sufficient weight to prior findings for this persisting causal hypothesis to be abandoned. A relatively strong association with alcohol was observed: Women drinking 20 g or more (two or more drinks) daily had 2.5 (odds ratio) times the risk of melanoma as nondrinkers (95% confidence interval, 0.87 to 7.4). However, previous data are inconsistent. With regard to potential protective factors, our data fit with prior speculation that antioxidants (beta-carotene and vitamin E), zinc, and iron warrant further investigation. The nonsignificant (P = 0.18) 40% reduction in risk seen for those eating the most fish (> or = 15 g daily versus < 5 g) suggests the effects of marine oils and omega-3 fatty acids may deserve specific attention.

Queensland has the highest incidence of cutaneous melanoma in the world, and the reported incidence has more than doubled in the last 15 years. The general geographical distribution of melanoma patients correlates negatively with latitude on a world scale. This suggests that exposure to solar ultraviolet rays is aetiologically important. The geographical distribution of melanoma patients in Queensland was examined by reviewing the residential addresses of all incident cases in a 12-month period from July 1, 1979, and no association with latitude was found. Rather there was a significantly increased incidence of melanoma in coastal, compared to inland, regions. When the distribution of doses of erythemal solar ultraviolet radiation in Queensland is examined, taking into account the effects of cloud cover, surface reflectance, and human behaviour, the observed regional differences in incidence may yet be explained by the variation in actual exposure to ultraviolet radiation received by the population.

The relationship between common acquired naevi and malignant melanoma of the skin was assessed in a case-control study. IN 183 patients and 183 controls matched for sex, age and area of residence, there was a strong association between the presence of pigmented naevi on the arms and melanoma. In comparison with persons having no naevi on the arms, the crude relative risk of melanoma was 28.0 when naevi were present. After adjusting for hair colour, propensity to sunburn and lifetime sun exposure, the final risk estimate was 30.1. Family history did not appear to be a determinant of disease independent of the above risk factors.

In a group of 211 schoolchildren in Queensland less than 12 years of age, the mean total melanocytic nevus (mole) count was 28 (median 19), and the mean count for raised nevi was 11 (median 8). The upper aspect of the back and chest were the most commonly affected sites, with the neck being the third. Boys had significantly (p less than 0.01) more melanocytic nevi than girls, and prevalence was highest in children with pale skin and light-colored hair. Nonwhite heritage had a protective effect independent of pigmentary characteristics. Total numbers of nevi on children also were related to maternal tendency to large numbers of moles and to family history of melanoma. The only significant association observed for the presence of large (greater than 5 mm) nevi on children was a family history of melanoma. The children studied come from a general population that has the highest known risk of melanoma. In Australia they have been shown to have the highest prevalence of nevi ever reported in the prepubertal age group. These descriptive data, together with the specific pigmentary and family associations described, extend the known links between benign nevi and malignant melanoma.

We investigated the relationship between cutaneous malignant melanoma and multiple sunburns in the Queensland population. Interview data were gathered from 236 case-control pairs concerning their lifetime experience of severe sunburns, their occupational and recreational sun exposure, and their skin type. Excluding the lentigo maligna melanoma subtype, an association between multiple sunburns and melanoma was evident. After controlling for other major risk factors there was a significant dose-response relationship (P less than 0.05): the estimated relative risk associated with 2-5 sunburns in life was 1.5, and with 6 or more was 2.4. This observation extends the hitherto circumstantial evidence of a causal relationship between exposure to solar ultraviolet radiation and melanoma, and suggests that precautionary measures could prevent the development of this disease in a proportion of cases in fair-skinned populations.