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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.)

Objective: To estimate the separate effects of sunlamp and tanning bed device use on melanoma risk., Methods: Population-based case-control study of 423 cases of melanoma and 678 controls in the state of New Hampshire. Exposure data, including sunlamp and tanning bed use, were collected by telephone interview. Associations were evaluated using logistic regression analyses., Results: About 17% of participants ever used a sunlamp, and most use (89%) occurred before 1980. The OR was 1.39 (95% CI 1.00-1.96) for ever using a sunlamp, 1.23 (95% CI 0.81-1.88) for those starting sunlamp use <20 years, and 1.71 (95% CI 1.00-2.92) for those starting >/=20 years. Data suggested increasing risk with number of sunlamp uses and with duration of use (tests of trend p = 0.02). The overall prevalence of tanning bed use was 22% and most use (83%) occurred after 1980. The OR was 1.14 (95% CI 0.80-1.61) for ever using a tanning bed; there was no evidence that risk increased with frequency or duration of use. The OR was 1.96 (95% CI 1.06-3.61) for having used both devices., Conclusion: Results suggest a modest association between sunlamp use and melanoma risk, and increasing risk with greater frequency and duration of use. No association with tanning bed use was found, but sufficient lag time may not have elapsed to assess a potential effect.

Only a few studies, conducted in Sweden, assessed factors associated with the presence of atypical moles in the general population. We conducted a population-based, case-control study in New Hampshire, USA, to identify factors associated with atypical moles. In our study, atypical moles affected 14% of the study population. The adjusted odds ratio (OR) was 0.34 (95% confidence interval (CI) = 0.14-0.80) for those with the highest adulthood recreational sun exposure, relative to the lowest. The OR for any freckles, compared to none, was 2.24 (95% CI = 1.18-4.25). We found a linear relationship between the number of benign moles and the presence of atypical moles (p for trend = 0.0001). The OR was 7.34 (95% CI = 3.03-17.80) for > 15 benign moles, relative to 0-4. Our data indicate that freckles and benign moles, which may reflect melanocytic inducibility, are strongly associated with atypical moles. The inverse association with sun exposure should be considered with caution.

Objective: To assess the frequency of occurrence and risk factors for multiple primary melanoma., Design: Population-based, case-control study., Setting: New Hampshire., Participants: Three-hundred fifty-four New Hampshire residents with a confirmed first diagnosis of cutaneous melanoma., Main Outcome Measure: Diagnosis of a subsequent primary cutaneous melanoma., Results: An additional melanoma occurred in 27 individuals (8%) within 2 years of their initial diagnosis, including 20 (6%) within the first postdiagnosis year. In 9 (33%) of these 27 cases, at least 1 subsequent melanoma was deeper than the first tumor. The 27 individuals with a subsequent melanoma diagnosis were classified as "cases" and were compared on the basis of risk factors to the 327 "controls" with a single melanoma diagnosis. The data indicate an inverse relation of risk of multiple primary melanomas with multiple blistering sunburns (P = .01 for the trend); the odds ratio (OR) was 0.32 (95% confidence interval [CI], 0.11-0.93) for 2 or more sunburns compared with none. The number of atypical moles was significantly related to increased risk (P = .004 for the trend). The presence of 3 or more atypical moles compared with none was associated with more than a 4-fold risk of multiple primary melanomas (OR, 4.29; 95% CI, 1.51-12.16)., Conclusions: Additional melanomas occur more frequently than previously shown. Our study confirms that atypical moles are strongly associated with risk of multiple primary melanomas but provides little evidence that risk is influenced by pigmentary characteristics, hours of sun exposure, or benign moles. The inverse association with blistering sunburn may reflect the influence of an unmeasured covariate.

Although benign and atypical moles are considered key melanoma risk factors, previous studies of their influence were small and/or institution-based. We conducted a population-based case-control study in the state of New Hampshire. Individuals of ages 20-69 with an incident diagnosis of first primary cutaneous melanoma were ascertained through the New Hampshire State Cancer Registry. Controls were identified through New Hampshire driver's license lists and frequency-matched by age and gender to cases. We interviewed 423 eligible cases and 678 eligible controls. Host characteristics, including mole counts, were evaluated using logistic regression analyses. Our results showed that pigmentary factors, including eye color (OR = 1.57 for blue eyes compared to brown), hair color (OR = 1.85 for blonde/red hair color compared to brown/black), freckles before age 15 (OR = 2.39 for freckles present compared to absent) and sun sensitivity (OR = 2.25 for peeling sunburn followed by no tan or a light tan and 2.42 for sunburn followed by tan compared to tanning immediately), were related to melanoma risk; these associations held after adjustment for sun-related factors and for moles. In analyses confined to skin examination participants, the covariate-adjusted effects of benign and atypical moles were moderately strong. Compared to 0-4 benign moles, risk increased steadily for 5-14 moles (OR = 1.71), 15-24 moles (OR = 3.55) and >or= 25 moles (OR = 4.33). Risk also increased with the number of atypical moles; compared to none, the ORs for having 1, 2-3, or >or= 4 atypical moles were 2.08, 1.84 and 3.80, respectively. Although risk was highest for those with multiple benign and atypical moles, the interaction was not of statistical significance. Our findings, arising from the first population- and incidence-based study to evaluate atypical moles in relation to melanoma risk, confirm the importance of host susceptibility, represented by pigmentary factors and the tendency to develop benign or atypical moles, in the etiology of this disease., ((c) 2005 Wiley-Liss, Inc.)

Objective: The importance of p16 alterations in the pathogenesis of dysplastic nevi and sporadic melanoma remains controversial. The goal of this work was to discover if p16/9p21 alterations occur early in precursor lesions as well as related sporadic melanomas., Methods: DNA was microdissected from 44 cutaneous melanomas, 14 dysplastic nevi, and six nevi without atypia as part of a study of melanoma. Alteration of the p16 region on 9p21 was measured by loss of heterozygosity (LOH) analysis as well as detection of homozygous deletions for p16 exon 2., Results: This analysis revealed that LOH in 9p21 directly surrounding p16 occurred in approximately 40% (17/44) of melanoma tumors representing all Clark levels. LOH was also discovered in 64% (9/14) of dysplastic nevi, and 50% (3/6) of benign nevi. Homozygous deletion of p16 was found in 29% (4/14) of dysplastic nevi but never in benign nevi., Conclusions: These studies reveal that LOH and homozygous deletion can affect 9p21 and the p16 locus early in putative precursor lesions of melanoma, even prior to the establishment of cytologically evident aberrant histology. Comparison of alterations in nevi and melanomas from the same individual revealed a pattern of progressive but heterogeneous events suggesting that systemic processes may affect this region of 9p21 at various times during melanoma progression.

Incidence of cutaneous melanoma has increased over the last several decades. Screening for melanocytic lesions is an effective approach to reducing incidence. This article presents information useful in melanoma screening, including histologic types of tumors, measurements, and anatomic sites. Causes of tumors, including ultraviolet radiation and the role of steroid hormones, are discussed. In addition, the presence of atypical and benign nevi is addressed.

We conducted a case-control study to identify factors associated with the presence of clinically atypical nevi. Potential participants were selected, using a two-staged sampling scheme, from a population-based cohort of 50,000 Swedish women who had responded to a previous health survey questionnaire. Of 500 women sampled for study recruitment, 400 (80%) agreed to participate. Study participants underwent a physician-conducted skin examination, which identified 130 women who had at least one clinically atypical nevus (cases) and 270 women without these lesions (controls). The physician-conducted skin examination also assessed women for benign nevus counts; other risk factor information was based upon responses to a health survey questionnaire. We found a strong and highly statistically significant relationship between number of benign nevi and the presence of at least one clinically atypical nevus (P < 0.0001). Women with 100 or more benign nevi had a 26-fold increased likelihood of having an atypical nevus. We noted statistically significant interactions between number of benign nevi and other factors of interest; thus, the results are reported separately for women with low (<50) or high (> or =50) counts of benign nevi. Among women with low counts of benign nevi, the likelihood of having an atypical nevus increased with degree of freckling; there was also a suggested role for early sun exposure. Among women with high counts of benign nevi, difficulty tanning and lack of peeling sunburns between ages 10 and 19 appeared to increase the likelihood of case status; our data also suggested an inverse relationship between parity and atypical nevi in this subgroup.

We conducted a validation study to assess laypersons' ability to self-report atypical nevi. Study subjects were drawn from a large population-based cohort of middle-aged Swedish women who had responded to a previous health survey. The health survey questionnaire included color photographs of atypical nevi. Respondents were asked to examine their lower extremities for similar lesions. We invited 500 survey respondents to participate in a physician-conducted skin examination; 400 (80%) subjects agreed. We compared the results of skin self-examination for atypical nevi to the results of the physician-conducted skin examination. Using methods developed for this study, we estimated sensitivity as 29% and specificity as 85%. Positive predictive value was 20%; negative predictive value was 90%. We estimated that 12% of Swedish women have atypical nevi on the lower extremities. Although these findings suggest poor accuracy of skin self-examination for atypical nevi, our results may have been adversely affected by limiting self-examination to the legs and by the severity of atypical nevi shown in the comparison photographs used by survey respondents.

A two-stage procedure for estimating sensitivity and specificity is described. The procedure is developed in the context of a validation study for self-reported atypical nevi, a potentially useful measure in the study of risk factors for malignant melanoma. The first stage consists of a sample of N individuals classified only by the test measure. The second stage is a subsample of size m, stratified according the information collected in the first stage, in which the presence of atypical nevi is determined by clinical examination. Using missing data methods for contingency tables, maximum likelihood estimators for the joint distribution of the test measure and the "gold standard" clinical evaluation are presented, along with efficient estimators for the sensitivity and specificity. Asymptotic coefficients of variation are computed to compare alternative sampling strategies for the second stage.

The aim of the present study was to evaluate the frequency with which histologically confirmed dysplastic nevi are observed among patients with superficial spreading melanoma compared to patients with nodular melanoma. A pathology review of 117 new cases of first primary nonfamilial cutaneous melanoma identified 61 patients with superficial spreading melanoma and 19 with nodular melanoma. Study participants received a physician-conducted skin examination which included enumeration of clinically benign and atypical nevi and the surgical excision of the clinically most atypical nevus. Patients' dysplastic nevus status was established by histological review of the clinically most atypical nevus. A comparison based on the tumor subtypes showed that dysplastic nevi occur nearly four times more frequently among patients with a prior diagnosis of superficial spreading melanoma relative to nodular melanoma (odds ratio = 3.6; P = 0.03).

There has been concern that individuals with nonfamilial melanoma and dysplastic melanocytic nevi (DMN) are not directly comparable to patients with hereditary melanoma and DMN. Because we have conducted a comprehensive study of nonfamilial melanoma over the past several years, we have addressed the above issue by directly comparing the characteristics of 145 nonfamilial patients, 6 patients with familial melanoma and the information available for familial melanoma in the literature. All 6 patients with familial melanoma had at least one first-degree blood relative with cutaneous melanoma. A large number of clinical and histologic variables were compared for both groups. Some pertinent variables included mean age at melanoma diagnosis 46.7 versus 52.3 years, mean Breslow thickness 2.11 versus 1.54 mm, mean total body nevi per patient 20.6 versus 18.3, mean total clinically atypical nevi per patient 2.0 versus 1.7 and total histologically confirmed DMN per group 22 (18.3%) versus 2 (33%), for patients with nonfamilial versus familial melanoma, respectively. No substantial differences were observed between the two groups. A review of the medical literature failed to reveal any quantitative data for melanocytic nevi, either clinical or histologic, at present that would allow distinction of patients with sporadic versus familial melanoma. We conclude that studies concerning the clinical characteristics of patients with DMN and nonfamilial melanoma are relevant to other persons with DMN including familial melanoma.

We studied 117 patients with nonfamilial melanoma to determine whether melanoma patients with dysplastic nevus syndrome might be distinguished, on the basis of solar exposure, from melanoma patients without dysplastic nevus syndrome. Study participants were interviewed and received a skin examination, which included a total count of nevi, a standardized assessment of clinically atypical nevi, and the excision of each patient's clinically most atypical nevus. Based on the histologic review of the clinically most atypical nevus, each patient was classified as to whether dysplastic nevus syndrome was present or absent. Childhood sunburn with blistering and childhood recreational sun exposure were found to be associated with dysplastic nevus syndrome. The results suggest that childhood sun exposure increases risk of melanoma by initiating the melanoma precursor syndrome.

Risk factors for multiple primary cutaneous melanoma were evaluated in a case-control study. Eight cases of multiple primary melanoma were matched on sex, age, and education to 24 first primary melanoma controls. Risk factors examined in the analysis included pigmentary characteristics, history of sun exposure, and nevi. The importance of histologically dysplastic nevi (DN) and clinically atypical nevi was of particular interest. Single-factor conditional logistic regression analysis showed that first primary melanoma patients with histological DN are at increased risk for a second primary (odds ratio, 6.2; 95% confidence interval, 1.2-33.4). Patients with two or more clinically atypical nevi also have elevated risk for a second primary (odds ratio, 8.8; 95% confidence interval, 1.0-80.7). Two-factor logistic models were used to evaluate the effect of histological DN while controlling singly for all other variables as potential confounders. Odds ratios for the association of histological DN varied from 6.1 to 10.4 when adjusting singly for pigmentary and sun exposure variables. In the two-factor model that included histological and clinical DN, both variables retained marginally significant statistical association with multiple primary melanoma. These results suggest that DN is a marker of increased risk for multiple primary melanoma and suggest that melanoma patients with evidence of DN should be followed closely for the development of additional primaries.