Development and validation of a melanoma risk score based on pooled data from 16 case-control studies.

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.

Biologic markers of sun exposure and melanoma risk in women: pooled case-control analysis.

A model has been proposed whereby melanomas arise through two distinct pathways dependent on the relative influence of host susceptibility and sun exposure. Such pathways may explain site-specific patterns of melanoma occurrence. To explore this model, we investigated the relationship between melanoma risk and general markers of acute (recalled sunburns) and chronic (prevalent solar keratoses) sun exposure, stratified by anatomic site and host phenotype. Our working hypothesis was that head and neck melanomas have stronger associations with solar keratoses and weaker associations with sunburn than trunk melanomas. We conducted a collaborative analysis using original data from women subjects of 11 case-control studies of melanoma (2,575 cases, 3,241 controls). We adjusted for potential confounding effects of sunlamp use and sunbathing. The magnitude of sunburn associations did not differ significantly by melanoma site, nevus count or histologic subtype of melanoma. Across all sites, relative risk of melanoma increased with an increasing number of reported lifetime "painful" sunburns, lifetime "severe" sunburns and "severe" sunburns in youth (p(trend) < 0.001), with pooled odds ratios (pORs) for the highest category of sunburns versus no sunburns of 3.22 [95% confidence interval (CI) 2.04-5.09] for lifetime "painful" sunburns, 2.10 (95%CI 1.30-3.38) for lifetime "severe" sunburns and 2.43 (95%CI 1.61-3.65) for "severe" sunburns in youth. Solar keratoses strongly increased the risk of head and neck melanoma (pOR 4.91, 95%CI 2.10-11.46), but data were insufficient to assess risk for other sites. Reported sunburn is strongly associated with melanoma on all major body sites.

Sun exposure and melanoma risk at different latitudes: a pooled analysis of 5700 cases and 7216 controls.

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.

Nevus density and melanoma risk in women: a pooled analysis to test the divergent pathway hypothesis.

A "divergent pathway" model for the development of cutaneous melanoma has been proposed. The model hypothesizes that melanomas occurring in people with a low tendency to develop nevi will, on average, arise more commonly on habitually sun-exposed body sites such as the head and neck. In contrast, people with an inherent propensity to develop nevi will tend to develop melanomas most often on body sites with large melanocyte populations, such as on the back. We conducted a collaborative analysis to test this hypothesis using the original data from 10 case-control studies of melanoma in women (2,406 cases and 3,119 controls), with assessment of the potential confounding effects of socioeconomic, pigmentary and sun exposure-related factors. Higher nevus count on the arm was associated specifically with an increased risk of melanoma of the trunk (p for trend = 0.0004) and limbs (both upper and lower limb p for trends = 0.01), but not of the head and neck (p for trend = 0.25). The pooled odds ratios for the highest quartile of nonzero nevus count versus none were 4.6 (95% confidence interval (CI) 2.7-7.6) for melanoma of the trunk, 2.0 (95% CI 0.9-4.5) for the head and neck, 4.2 (95% CI 2.3-7.5) for the upper limbs and 3.4 (95% CI 1.5-7.9) for the lower limbs. Aggregate data from these studies suggest that high nevus counts are strongly associated with melanoma of the trunk but less so if at all of the head and neck. This finding supports different etiologic pathways of melanoma development by anatomic site.

A pooled analysis of melanocytic nevus phenotype and the risk of cutaneous melanoma at different 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.

Anthropometric factors and risk of melanoma in women: a pooled analysis.

Anthropometric factors such as height, weight and body mass index are related to the occurrence of certain malignancies in women including cancers of the breast, ovary and endometrium. Several studies have investigated the relation between height and weight or body mass and the risk of cutaneous melanoma in women, but results have been inconsistent. We conducted a collaborative analysis of these factors using the original data from 8 case-control studies of melanoma in women (2,083 cases and 2,782 controls), with assessment of the potential confounding effects of socioeconomic, pigmentary and sun exposure-related factors. Women in the highest quartile of height had an increased risk of melanoma [pooled odds ratio (pOR) 1.3, 95% confidence interval (CI) 1.1-1.6]. We also found an elevated risk associated with weight gain in adult life of 2 kg or more (pOR 1.5, 95% CI 1.1-2.0). Stratifying by age at melanoma diagnosis (<50, >or=50 yr), we found this risk greater among women <50 yr of age. Associations were unaffected by adjustment for other known risk factors for melanoma. There was no evidence that the effects varied for different histologic subtypes of cutaneous melanoma. There was no association with body weight per se, body mass index, or body surface area, either recent or in young adulthood. In aggregate, data from these studies suggest that greater height and weight gain may be risk factors for cutaneous melanoma in women.

Is 2,3,5-pyrroletricarboxylic acid in hair a better risk indicator for melanoma than traditional epidemiologic measures for skin phenotype?

This study aims to assess type of melanin as a risk indicator for skin tumors, in a sample of melanoma cases and controls within a larger multicenter study (Helios 2), held in Europe and South America in 2001-2002. In each case and control, the melanin content in hair was assessed by three methods: 1) the amount of 2,3,5-pyrroletricarboxylic acid (PTCA); 2) the absorbance ratio with ultraviolet spectroscopy; and 3) the spectra of near-infrared spectroscopy. Statistical analysis was performed in a Bayesian setting, defining priors for confounders and effect modifiers from the larger study data set. Subjects with values of PTCA of less than 85 ng/mg carried an increased risk (26 vs. seven discordant pairs: odds ratio = 4.4, 95% confidence interval: 1.52, 14.54), adjusted by hair color, eye color, and number of nevi (n = > or =40). The absorbance ratio showed a weaker and nonsignificant odds ratio of 1.5. After correction by misclassification, near-infrared spectroscopy was associated with an odds ratio of 2.3 (95% confidence interval: 1.36, 4.22). The amount of PTCA is thus a strong and independent risk indicator for melanoma. Incorporating PTCA determination into epidemiologic studies is therefore recommended.

Pregnancy history and incidence of melanoma in women: a pooled analysis.

There is evidence that pregnancy history including age at first birth and parity may play a role in risk of cutaneous melanoma in women, although, epidemiological findings are inconsistent. We conducted a collaborative analysis of these factors using the original data from ten completed case-control studies (2391 cases and 3199 controls), and assessed the potential confounding effects of socioeconomic, pigmentary, and sun exposure-related factors. We found no overall association with ever having a live birth (pooled odds ratio (pOR) 0.95, 95% confidence interval (CI) 0.67-1.35). However, we detected a reduced risk of melanoma among women with higher parity (> or = 5 versus no live births pOR 0.76, 95% CI 0.49-1.18, each live birth pOR 0.95, 95% CI 0.91-0.99, p trend = 0.05). Women with both earlier age at first birth (e.g., <20 years) and higher parity (e.g., > or = 5 live births) had a particularly lower risk than women with later age at first birth (e.g., > or = 25 years) and lower parity (e.g., <5 live births) (pOR 0.33, 95% CI 0.14-0.75). The results are compatible with an effect of reproductive history-related factors on melanoma risk, but also could reflect differences in other factors, such as sun exposure history.