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Background: Cutaneous melanoma incidence varies consistently across body sites between men and women, but the underlying causes of these differences remain unclear. To date, no prospective studies have examined risk factors for melanoma separately for men and women according to body site., Objectives: We aimed to examine the association between identified constitutional, genetic and environmental risk factors for invasive melanoma of different body sites among men and women., Methods: We compared the association between constitutional, genetic and environmental risk factors for invasive melanoma on different body sites separately for men and women in a population-based prospective cohort study of 17 774 men and 21 070 women aged between 40 and 69 years who were residents of Queensland, Australia at baseline in 2011. Participants were followed until December 2021. We examined risk factors including hair colour, tanning ability, naevus density and proxies for high cumulative sun exposure, all self-reported at baseline. We also examined polygenic risk score (PRS) derived from summary statistics from a melanoma genome-wide association study meta-analysis., Results: During a median 10.4 years of follow-up, 455 men and 331 women developed an incident invasive melanoma; the mean age at diagnosis was lower in women than in men (62.6 vs. 65.0 years). The most common body site was the trunk in men (45.1%), and the upper (36.8%) and lower limbs (27.4%) in women. High naevus density and proxy measures of high cumulative sun exposure were similarly associated with melanoma at all sites in men and women. In both sexes, high genetic risk was associated with melanoma on all body sites except the head and neck. We observed differences between men and women in the association between PRS and melanoma of the trunk [highest vs. lowest tertile of PRS: hazard ratio (HR) 2.78, 95% confidence interval (CI) 1.64-4.69 for men; HR 1.55, 95% CI 0.63-3.80 for women] and nonsignificant but large differences for the lower limbs (HR 5.25, 95% CI 1.80-15.27 for men; HR 1.75, 95% CI 0.88-3.47 for women)., Conclusions: While there are a number of potential explanations for these findings, this raises the possibility that genetic factors other than those related to pigmentation and naevus phenotypes may play a role in the predilection for melanoma to arise on different sites in men and women., Competing Interests: Conflicts of interest The authors declare they have no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Background: Malignant melanoma (MM) is increasing rapidly in Northern Europe. To reduce incidence and mortality through earlier diagnosis, public awareness of MM is important. Thus, we aim to examine awareness of risk factors and a symptom of MM, and how awareness varies by country and socio-demographic factors in Denmark, Northern Ireland (NI), Norway and Sweden., Methods: Population-based telephone interviews using the 'Awareness and Beliefs about Cancer' measure were conducted in 2011 among 8355 adults ≥50 years as part of the International Cancer Benchmarking Partnership Module 2. Prevalence ratios (PRs) with 95% confidence intervals were calculated., Results: In these four countries, lowest awareness was found for 'sunburn in childhood' (63%), whereas awareness was high for 'use of sunbeds' (91%) and 'mole change' (97%). Lack of awareness of 'sunburn in childhood' was more prevalent among respondents from Norway [PR = 1.38 (1.28-1.48)] but less prevalent among respondents from Northern Ireland (NI) [PR = 0.78 (0.72-0.85)] and Sweden [PR = 0.86 (0.79-0.93)] compared with respondents from Denmark. Lack of awareness of 'use of sunbeds' was more prevalent among respondents from Norway [PR = 2.99 (2.39-3.74)], Sweden [PR = 1.57 (1.22-2.00)], and NI [PR = 1.65 (1.30-2.10)] compared with respondents form Denmark. Being a man, age ≥70, living alone, and having lower education, were each independently associated with lack of MM-awareness., Conclusions: The results indicate relatively low awareness of 'sunburn in childhood' as a risk factor for MM, and important disparities in MM-awareness across countries and socio-demographic groups. Improved and more directed initiatives to enhance public MM-awareness, particularly about 'sunburn in childhood', are needed., (© The Author 2015. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.)

Background: Heritability of naevi counts is widely acknowledged as a potential surveillance parameter for prevention purposes. The contribution of heritability to the changes seen in naevus number and morphology over time and their corresponding dermoscopic characteristics is unknown, but is important to understand in order to account for adequate prevention measures., Objectives: To identify naevus characteristics that are strongly influenced by heritability., Methods: This cross-sectional study included 220 individuals [76 monozygotic (MZ), 144 dizygotic (DZ)], recruited from the Brisbane Twin Naevus Study. Participants received full body imaging and dermoscopy of naevi ≥ 5 mm in diameter. Dermoscopic type, total naevus count (TNC), change in TNC with age, and naevus distribution, size, colour and profile were compared between MZ and DZ twins. Heritability of these traits was assessed via Falconer's estimate., Results: Significant differences were found in comparing MZ and DZ twins for TNC, numbers of naevi 5·0-7·9 mm in diameter, counts of light-brown naevi, naevi on the back and sun-protected sites, and naevi with the 'nonspecific' dermoscopic pattern., Conclusions: This study strongly supports a heritable component to TNC, as well as changes in TNC, and the number of medium-sized naevi, light-brown naevi, specific sites and certain dermoscopic features in adults. These characteristics should be taken into account by naevus surveillance programmes and further studied to identify candidate gene associations for clinical and dermoscopic patterns in conjunction with melanoma risk stratification., (© 2015 British Association of Dermatologists.)

Background: Despite recent discoveries of germline and somatic mutations in melanoma, naevus count remains the most important risk factor for melanoma. Counting naevi on the whole body is time consuming. In order to identify patients at risk for melanoma, many studies have used naevus count on selected body sites as a proxy for total body naevus count (TBNC)., Objectives: The main aim of this study was to assess the predictive value of naevus count on 17 different body sites in estimating TBNC in a large cohort of healthy U.K. Caucasian female subjects. Once the site with the best predictive value for TBNC was determined, a second aim was to estimate the cut-off values of naevus counts at this anatomical site that best predict the presence of 50 or 100 naevi, respectively., Methods: The most predictive body site for TBNC was assessed in a cohort of healthy female twins. This finding was replicated on a control group from a U.K. case-control study and a prediction model was performed afterwards. The area under the receiver operating characteristics curve was used to evaluate the best cut-off for the prediction of having a TBNC of more than 50 or 100., Results: There were 3694 female twins included. The TBNC showed a steady decline after the age of 30 years (P < 0·001). The most predictive sites for TBNC were the arms and legs: the adjusted correlation coefficients were 0·50 and 0·51 (P < 0·001) for the right and left arm, respectively, and 0·49 and 0·48 for the right and left legs, respectively (P < 0·001). The arm remained the most predictive site for TBNC when replicated in a control population including both sexes. In the twin study, women with more than 11 naevi on the right arm were approximately nine times more likely to have more than 100 naevi (odds ratio = 9·38, 95% confidence interval 6·71-13·11)., Conclusions: The ability to estimate TBNC quickly by counting naevi on one arm could be a very useful tool in assessing melanoma risk in primary care., (© 2015 British Association of Dermatologists.)

Background: Sunscreen is recommended to prevent sunburn and skin cancer., Objectives: To investigate sunscreen use in relation to demographic and phenotypic characteristics among women in Norway, as well as solar UV exposure, sunburn experience in different decades of life, and temporal trends in sunscreen use., Methods: We used data from the Norwegian Women and Cancer Study, a large population-based prospective cohort study. Log-binomial regression was used to estimate the association between sunscreen use and personal characteristics. Results are presented as prevalence ratios (PRs) and 99% confidence intervals (CIs)., Results: The study sample consisted of 148,869 women, with a mean age, when answering the questionnaire, of 53 years (range 41-75). Sixty-five per cent of the women used sunscreen during the Easter holiday, 73% in northern latitudes and 87% in bathing vacations in southern latitudes. Sunscreen with sun protection factor (SPF) ≥ 15 was used by 25,156 (18%) at Easter, 18,118 (13%) in northern latitudes and 22,678 (30%) in southern latitudes. The prevalence of sunscreen use increased from 1997 to 2007, and this increase was associated with age. In 1997, 39% of women reported at least one sunburn per year in the recent decade, compared with 46% in 2007 (Ptrend = 0·001). Women who experienced at least four sunburns per year during adolescence reported more sunscreen use in adulthood (PREaster 1·54, 99% CI 1·30-1·83; PRnorthern latitudes 1·49, 99% CI 1·20-1·84; PRsouthern latitudes 1·37, 99% CI 1·14-1·65)., Conclusions: The prevalence of sunscreen use increased from 1997 to 2007. However, this increase has not been accompanied by a decrease in sunburn. Moreover, use of sunscreen with the recommended SPF was not common among Norwegian women., (© 2014 British Association of Dermatologists.)

Objectives: The clinical significance of nevus-associated melanoma compared with de novo melanomas remains controversial. It has been suggested that nevus-associated melanomas have a higher Breslow thickness and therefore worse prognosis. Over a 10-year period, this study evaluated the incidence of nevus-associated melanoma and its prognostic significance related to clinicopathologic features., Methods: Cross-sectional study from 1995 through 2004 in a dermatopathology referral center. With available data, we evaluated sex, primary location, histologic subtype, Breslow thickness, Clark level, presence of ulceration, associated lesion, and histologic subtype of the associated lesion., Results: Of 135,653 pathologic records from skin biopsy specimens over a 10-year period, 1,190 melanoma records were selected. Nevus-associated melanomas corresponded to 390 (32.8%) melanomas, with thin melanomas having a nevus 1.52 times the association observed with thick melanomas (>1.01 mm; 95% confidence interval, 1.16-1.99; P < .001). Superficial spreading melanoma was the most frequent, while no lentigo maligna melanoma was associated with nevi. The median Breslow thickness of nevus-associated melanomas was lower than that of de novo melanomas., Conclusions: Nevus-associated melanomas, which represent one-third of the melanomas in southeast Brazil, are associated with intermittent sun exposure, superficial spreading melanomas, and lower Breslow thickness. This is one of the largest series describing nevus-associated melanomas in Latin America., (Copyright© by the American Society for Clinical Pathology.)

There is a paucity of data on basal-cell carcinoma (BCC) in the United States, since most national registries do not collect information on BCC. We evaluated BCC incidence trends and associated risk factors for BCC in 140,171 participants from a U.S. female cohort, the Nurses' Health Study (1986-2006), and a U.S. male cohort, the Health Professionals' Follow-up Study (1988-2006). Age-adjusted BCC incidence rates increased from 519 cases per 100,000 person-years to 1,019 cases per 100,000 person years for women and increased from 606 cases per 100,000 person-years to 1,488 cases per 100,000 person-years for men during the follow-up period. Cox proportional hazards analysis identified the following phenotypic risk factors for BCC in both cohorts: family history of melanoma, blond or red hair colors, higher number of extremity moles, higher susceptibility to sunburn as a child/adolescent, and higher lifetime number of severe/blistering sunburns. The multivariate-adjusted risk ratio for the highest quintile of cumulative midrange ultraviolet B flux exposure versus the lowest quintile was 3.18 (95% confidence interval: 2.70, 3.76) in women and 1.90 (95% confidence interval: 1.57, 2.29) in men. BCC incidence was generally higher in men than in women, and BCC risk was strongly associated with several phenotypic and exposure factors, including midrange ultraviolet B radiation, in our study populations.

Background: Concern about skin cancer is a common reason for people from predominantly fair-skinned populations to present to primary care doctors., Objectives: To examine the frequency and body-site distribution of malignant, pre-malignant and benign pigmented skin lesions excised in primary care., Methods: This prospective study conducted in Queensland, Australia, included 154 primary care doctors. For all excised or biopsied lesions, doctors recorded the patient's age and sex, body site, level of patient pressure to excise, and the clinical diagnosis. Histological confirmation was obtained through pathology laboratories., Results: Of 9650 skin lesions, 57·7% were excised in males and 75·0% excised in patients ≥ 50 years. The most common diagnoses were basal cell carcinoma (BCC) (35·1%) and squamous cell carcinoma (SCC) (19·7%). Compared with the whole body, the highest densities for SCC, BCC and actinic keratoses were observed on chronically sun-exposed areas of the body including the face in males and females, the scalp and ears in males, and the hands in females. The density of BCC was also high on intermittently or rarely exposed body sites. Females, younger patients and patients with melanocytic naevi were significantly more likely to exert moderate/high levels of pressure on the doctor to excise., Conclusions: More than half the excised lesions were skin cancer, which mostly occurred on the more chronically sun-exposed areas of the body. Information on the type and body-site distribution of skin lesions can aid in the diagnosis and planned management of skin cancer and other skin lesions commonly presented in primary care., (© 2011 The Authors. BJD © 2011 British Association of Dermatologists 2011.)

Background: Scanty information is available on the prevalence of congenital melanocytic naevi (CMN) and congenital naevus-like naevi (CNLN), particularly the small ones., Objectives: To estimate the prevalence of CMN/CNLN in Italian schoolchildren, and to assess variations according to potential risk factors for melanoma., Methods: We conducted a survey in 13 Italian areas on 3406 schoolchildren aged 12-17 years. Children were examined by dermatologists who assessed pigmentary traits and made a count of small (6-15 mm in diameter) and medium/large (> 15 mm) CMN/CNLN on 19 anatomical areas., Results: Overall, 592 children (17.4%) had one or more CMN/CNLN. Prevalence of small CMN/CNLN was 16.1%, and that of medium/large CMN/CNLN was 1.8%. There was no difference between age groups and sexes. CMN/CNLN were more frequent in children with a higher number of common melanocytic naevi (multivariate odds ratio, OR = 7.1 for the highest vs. the lowest quartile), consistent in small (OR = 7.2) and medium/large CMN/CNLN (OR = 6.0). Family history of malignant melanoma (OR = 1.4) and personal history of diabetes (OR = 4.4) appeared to be directly, and sun exposure inversely associated with CMN/CNLN. No relation was evident between CMN/CNLN and pigmentary traits, anthropometric characteristics, dietary habits, freckles, sunburns, sunscreen use or history of selected diseases., Conclusions: The association with family history of melanoma, the strong association with acquired melanocytic naevi, and the lack of association with pigmentary traits and sunburns suggest that CMN/CNLN may act as an independent risk marker for subjects at increased risk for cutaneous melanoma later in life.

Scanty information is available on the relation between nevus count on specific anatomic areas and the total body surface, particularly in children. The authors analyzed this issue by using data from a uniquely large study conducted in 1997 on 3,406 schoolchildren (1,746 boys and 1,660 girls) aged 13-14 years in 13 cities from northern, central, and southern Italy. Children were examined by trained dermatologists who counted melanocytic nevi (>or=2 mm in diameter) on 19 different anatomic sites. Overall, the mean number of nevi was 17.3 (18.6 in boys and 15.8 in girls). The adjusted correlation coefficients (r) with number of nevi on the whole body were 0.74 for head and neck, 0.83 for anterior and 0.84 for posterior trunk, and 0.88 for upper and 0.80 for lower limbs. With reference to single anatomic sites, the best predictor of total nevus count was the lateral arms (r=0.80), overall and in strata of sex and pigmentary characteristics. This large study provides definite evidence that examining the upper limbs only, particularly the lateral arms, is a practical and suitable tool for predicting total nevus count in children.

Background: The population-based case-control study is not suited to the evaluation of rare genetic (or environmental) factors. The use of a novel case-control design in which cases have second primaries and controls are cancer survivors has been proposed for this purpose., Methods: We report results from an international study of melanoma that involved population-based ascertainment of incident cases of second or subsequent primary melanoma as the 'case' group and incident cases of first primary melanoma as the 'control' group. We evaluate the validity of the study design by comparing the results obtained for phenotypic factors that have been shown consistently to be associated with melanoma in previous conventional studies with the results from a conventional case-control study conducted in Connecticut and from literature reviews., Results: All but one of the known risk factors for melanoma were shown to be significantly associated with melanoma in our study, though the individual odds ratios appear to be somewhat attenuated relative to the magnitudes typically observed in the literature., Conclusions: Patients with a second or subsequent primary cancer of a single type represent a potentially valuable and under-utilized resource for the study of cancer aetiology.

Background: It is unclear which of the number or the density of naevi on the skin is the more appropriate measure of risk of melanoma. Furthermore, the relationship between the number of naevi and their density in an individual has not been explored. Thus, for example, it is unknown if larger people tend to have more naevi by virtue of having a larger skin area, or if the density of naevi is similar in people of different body sizes. In this study, we explored the relationship between the number and the density of naevi in a sample of adolescents., Subjects and Methods: A sample survey of naevi in 472 grade 9 secondary school students (aged 14-15 years) was conducted in Tasmania, Australia during 1992, and a subset of these individuals was followed up in 1997. Counts of naevi of various sizes were taken on the arm, leg, and back. Naevus density was estimated by using an algorithm to estimate body surface area from the height and weight of an individual. More general relationships of the naevus counts to height and weight were also explored. Finally, we considered whether the relationship between naevus density and the anthropometric variables could be confounded by exposure to ultraviolet radiation., Results: The mean number of naevi was very similar in the two samples. Naevus density was slightly lower in the 1997 sample, mainly because of increasing body size in the cohort. The numbers of naevi were only weakly related to height and weight in males, and there was essentially no relationship in females. Regression analysis showed significant relationships of weight to the back naevus counts in males in 1992 and 1997, and to the arm naevus count in males in 1997; otherwise, none of the regression coefficients for height and weight were statistically significant. This picture did not change following adjustment for potentially confounding variables indicating time spent outdoors or in the sun. Furthermore, there was no evidence that time spent in the sun was related to the body mass index., Conclusions: It appears that the number and density of naevi in an individual are unrelated. Accordingly, with the present state of knowledge concerning the risk of melanoma, both the number and density of naevi should be considered as equally valid in future studies as markers of the risk of melanoma, and in studies on the natural history of naevi. If the disease mechanism is systemic, and not related to particular naevi, naevus density might form the better marker of risk. However, if the disease mechanism is related to effects on particular naevi, then the risk would vary in proportion to the number of naevi.

The Kidskin Study is a 5-year intervention study (1995-1999) involving 1,776 5- and 6-year-old children attending 33 primary schools in Perth, Western Australia. The aim of the study is to design, implement, and evaluate an intervention to reduce sun exposure in young children. There are three study groups: a control group, a "moderate intervention" group, and a "high intervention" group. The control schools receive the standard Western Australian health education curriculum, while the moderate and high intervention schools receive a specially designed curricular intervention. In addition, children in the high intervention group receive program materials over the summer holidays, when exposure is likely to be highest, and are offered sun-protective swimwear at low cost. The main outcome measure is the number of nevi on the back. Other outcomes include nevi on the chest (boys only), face, and arms, levels of suntanning, degree of freckling, and sun-related behaviors. At baseline, the three groups were similar with respect to nevi and freckling after adjustment for observer and month of observation. Sun exposure was slightly higher in the high intervention group. The groups were also similar with respect to most potential confounders, although they differed with respect to Southern European ethnicity and parental education.

Virtually nothing is known about the prevalence of skin conditions in children in the general population. Although we know something about the relative frequency of skin conditions seen by dermatologists, we do not know how such referrals are influenced by factors such as social class, accessibility to medical services or educational and cultural background. In order to estimate the burden and relative frequency of dermatological disease in children in the community, we measured the point prevalence of skin conditions in 1114 Romanian schoolchildren aged 6-12 years, using the British Association of Dermatologists diagnostic index. The overall point prevalence of children with one or more skin diseases was 22.8%, with no significant differences according to age group or sex, except for pityriasis alba which showed a male predominance (P = 0. 007). The most common diseases were infectious dermatoses such as viral warts and insect bites (6.3%), dermatitis/eczema (5.1%), pityriasis alba (5.1%), keratosis pilaris (4.0%) and urticaria (1. 9%). Together, these five groups accounted for more than 84% of the cases. Of the 1114 children, 213 (19.1%) had only one skin disease and 41 (3.7%) had two skin diseases. While acknowledging the limitations in defining which skin conditions can benefit from medical care, this study suggests that skin disorders are common in Romanian schoolchildren, affecting about one-quarter of 6-12 year olds. Such a point prevalence is likely to be conservative because of the tendency of prevalence estimates to exclude many other dermatoses of short duration. The finding that over 80% of the disorders can be grouped into fewer than six categories is important in informing training programmes and delivery of service for primary health care teams. This study provides a baseline for further studies into the morbidity and use of health care services by children with skin disease in the community.

Background: Previous epidemiologic studies have suggested that sunscreen use is associated with an increased risk of melanoma skin cancer. Because high nevi (mole) count in adults is a strong predictor of melanoma, we conducted a study examining the number of nevi in 6- to 7-year-old European children, according to their sunscreen use., Methods: Whole-body and site-specific counts of nevi 2 mm or larger were performed in 631 children in their first year of primary school in four European cities. Independently, parents were interviewed regarding sun exposure, sunscreen use, and physical sun protection of their child., Results: After adjustment for sun exposure and host characteristics (e.g., skin phototype, eye color), the relative risk for high nevus count on the trunk was 1.68 (95% confidence interval [CI] = 1.09-2.59) for the highest level of sunscreen use and 0.59 (95% CI = 0.36-0.97) for the highest level of wearing of clothes while in the sun. The sun protection factor had no effect on nevus counts despite a high median value of 17.4. Sunburn number was not associated with nevus count. The highest risk associated with sunscreen use was found among children who had never experienced sunburn., Conclusions: In white, European children, sunscreen use appears to be associated with development of nevi, probably because it allows longer sun exposures. Wearing clothes may be an effective way to prevent proliferation of nevi. Since a high nevus count is a strong predictor of melanoma, sunscreen use may be involved in melanoma occurrence because it may encourage recreational sun exposure.

The study population consisted of the 95 patients who presented with cutaneous malignant melanoma in the west of Scotland between 1979 and 1986 and who were aged under 30 at the time of diagnosis. Over this 7-year period, 1299 melanomas were diagnosed in all age groups in this geographical area, increasing in incidence by 82% from 135 in 1979 to 246 in 1986. The proportion of melanomas diagnosed before the patients' thirtieth birthday remained constant at 6%. None were diagnosed in the under-15 age-group, and none developed on giant congenital naevi. Forty-two of the 95 melanomas (44%) in the under-30 group developed on a small naevus present either from birth or early childhood. These melanomas were thicker than those apparently developing on normal skin, but once controlled for tumour thickness and sex the presence of a pre-existing naevus did not affect 5-year survival. The overall 5-year survival was 76% with poorer survival associated with thicker tumours and male sex. This study suggests that small early onset naevi may have a higher potential for post-pubertal malignant change than has been previously recognized.

The naevus profile was examined in a Swedish population that was randomly selected from a census file. The participation rate was considered high at 82%. The number of common naevi (CN) and the prevalence of dysplastic naevi (DN) were investigated in 379 subjects (aged 30-50 years). The mean total body count of CN greater than or equal to 2 mm was 67 (range 1-300). As many as 22% of the population had 100 naevi or more and only 18% had less than 25. The counts were not influenced by age or sex. DN were diagnosed clinically in 18% (CI 14-22%) of the subjects and histologically in 8% (CI 5-11%). Subjects with dysplastic naevi had a significantly larger number of common naevi and a more sun-sensitive skin type than subjects without DN, P less than 0.001.

The relation of the presence of moles (nevi) on all four limbs to risk of cutaneous malignant melanoma was explored among 98 incident cases aged 32-59 years at diagnosis and 190 age-matched controls drawn from the Nurses' Health Study, a prospective cohort of female nurses in the United States. Cases diagnosed during follow-up from 1976 to 1982 were included in this study. Participants reported counts of all moles and raised moles alone on postal questionnaires. Distributions of moles were similar for right and left sides on upper and lower limbs for cases and controls. Counts declined with increasing age for all women, from a median of 15 for the youngest tertile of controls (aged 36-46 years) to three for the oldest (aged 54-62 years). Cases had more moles than did controls (medians of 23 and 9, respectively, for total moles on all four limbs): The presence of any mole on a limb gave relative risks for melanoma ranging from 2.2 (95% confidence interval (CI) = 1.2-4.0) for one or more moles on an arm to 2.9 (95% CI = 1.6-5.3) for one or more moles on the lower limb. For raised moles, relative risks were 1.7 (95% CI = 1.0-2.7) for arm, 2.1 (95% CI = 1.3-3.5) for lower limb, and 3.5 (95% CI = 2.0-6.3) for leg (below knee). The highest site-specific risk (i.e., for any moles on the same limb as the melanoma vs. no moles on that limb) was for moles on the lower limb (relative risk = 5.0 (95% CI = 1.8-13.5)). There were positive and significant trends in overall and site-specific risk with increasing numbers of moles on all limbs when absolute mole counts were considered, e.g., for total moles on all four limbs combined, chi for trend = 4.0, one-sided p less than 0.001, with relative risk for more than 100 moles versus none of 6.0. Inclusion of sun exposure and other constitutional factors in logistic regression analyses did not alter these observed relations between the presence of moles and risk of melanoma.