EDNRB gene variants and melanoma risk in two southern European populations

Background. EDNRB gene variants were reported to be associated with melanoma risk in French patients, with the S305N variant showing the highest frequency. Aim. To verify the S305N association with melanoma risk in an independent larger French population (378 patients, 389 controls); to investigate the role of EDNRB variants in melanoma risk in an Italian population (133 patients, 118 controls); and to explore the association of CDKN2A or CDK4 mutations with the S305N EDNRB variant in a subgroup of patients (59 French, 12 Italian) with a suspected hereditary predisposition to melanoma (familial melanoma, sporadic multiple primary melanoma or melanoma associated with pancreatic cancer). Methods. The S305N variant was genotyped in the French population, while the EDNRB gene in the Italian population was entirely sequenced. Results. Overall, there was no significant difference in the frequency of the S305N variant between patients with sporadic melanoma and controls in either the French or the Italian population. However, a significantly higher S305N allele frequency was detected in French patients with a suspected hereditary predisposition to melanoma compared with controls (P = 0.04). In addition, in this subgroup of patients, the S305N allele was also significantly associated with the presence of CDKN2A mutations (P = 0.04). Conclusions. Our results showed no evidence of association of the S305N EDNRB polymorphism with sporadic melanoma risk in either the French or Italian populations, but there was an indication that EDNRB might be a melanoma‐predisposing gene in French patients with a suspected hereditary predisposition to melanoma.     

On naevi and melanomas in dysplastic naevus syndrome patients

Cutaneous melanoma may occur as isolated, so-called 'sporadic’cases or in association with multiple atypical naevi and in familial clusters, in which case it is referred to as the familial dysplastic naevus syndrome (DNS). In this retrospective study (a) the number and body distribution of naevocytic naevi and (b) the body distribution of malignant melanoma (MM) in individuals with familial DNS were compared in order to study their association. In 45 patients with familial DNS aged 20–39 years naevus counts on trunk and lower extremities were compared with melanoma data and distributions from a second group of 43 patients from the same DNS families aged 12–66 years. Men had significantly more naevi of a size 2 mm or 5 mm on the back than women (P=0.02). Women showed a tendency towards a greater number of naevi on the lower extremities than men, but in women no significant difference in naevi between the lower extremities and the back was found. The total number of naevi on the trunk and lower extremities in familial DNS patients was higher than that in the general population. In conclusion, it was found that predilection sites for melanoma in familial DNS patients of both sexes correspond with the distribution of naevi; in males naevi and melanoma counts and percentage distributions were higher on the back, in females both the back and the lower extremities were affected. These findings strongly suggest an association between naevus distribution and melanoma occurrence and sire in familial DNS, analogous to earlier reports on sporadic melanoma.^1,2     

Genetic variations of patients with familial or multiple melanoma in Southern Brazil

Background Patients with familial melanoma or multiple primary melanoma represent a high‐risk population to hereditary melanoma. Mutations in susceptibility genes, such as CDKN2A, CDK4 and MC1R, have been associated with the development of melanoma. Objectives The purpose of this study was to determine the genotypic background of patients with familial and/or multiple melanoma in southern Brazil. Methods This study analysed 33 cases (5 patients with multiple primary melanoma and 28 patients from families with at least two well documented cases) and 29 controls. Genomic analysis of CDKN2A and CDK4 genes by PCR‐SSCP analysis and sequencing and direct sequencing of MC1R were performed in all individuals. Results No functional mutations in CDKN2A or CDK4 were detected in the 62 individuals. Infrequent variants in polymorphic loci of CDKN2A gene were identified in 15 participants (24.2%) and 24/33 (72.8%) cases and 19/27 (70.4%) controls reported at least one infrequent variant in MC1R (P = 0.372). Furthermore, a non‐significant tendency towards an association between melanoma risk and MC1R variants G274A and C451T and a non‐significant linear tendency to the number of infrequent high‐risk variants in MC1R were observed. Conclusions These results suggest that in southern Brazilian population, CDKN2A or CDK4 germinal alterations may have a weaker influence than previously thought and environmental risk factors may play a central role in melanoma susceptibility. However, considering the tendency observed for gene MC1R, low‐penetrance genes may be a relevant aetiological factor in southern Brazil with fair skin population and high sunlight exposure.     

Familial and sporadic melanoma: different clinical and histopathological features in the Italian population – a multicentre epidemiological study – by GIPMe (Italian Multidisciplinary Group on Melanoma)

Background Having a familial member affected by cutaneous melanoma is a risk factor for this neoplasm. Only a few epidemiological case–control studies have been carried out to investigate whether familial and sporadic melanomas show different clinical and histopathological features. Objective The aim of this study was to evaluate eventual different features and risk factors in subjects affected by familial and sporadic cutaneous melanoma. Methods A case–control multicentre study interesting 1407 familial (n = 92) and sporadic (n = 1315) melanomas in the Italian population. The analysis was made using t‐test for continuous variables and chi‐squared test for categorized ones. The variables which have shown statistically significant differences in the two groups in the univariate analysis were included in a multivariate model. Results The results showed some main significantly clinical differences between the two groups investigated: earlier age at diagnosis, a greater proportion of sunburns and a higher number of naevi were observed for the familial cases compared with sporadic ones. Nevertheless, we did not find a diagnostic anticipation in familial melanomas, in fact the invasion level and the thickness of melanomas was similar in the two groups. Conclusion Some relevant clinical differences are observed between the two groups examined. The familial melanoma members, although carriers of constitutional risk factors, are not careful enough to primary and secondary prevention.     

A flexible multiplex bead-based assay for detecting germline CDKN2A and CDK4 variants in melanoma-prone kindreds

The presence of recurrent high-risk mutations in cyclin-dependent kinase inhibitor 2A/cyclin-dependent kinase 4 (CDKN2A/CDK4) among melanoma-prone families suggests that a high-throughput, multiplex assay could serve as an effective initial screening tool. To this end, we have developed a multiplex bead-based assay for high-throughput CDKN2A/CDK4 genotyping in the context of familial melanoma. Genomic DNA from 1,603 subjects (1,005 in training set and 598 in validation set) were amplified by multiplex PCR using five CDKN2A/CDK4 primer sets followed by multiplex allele-specific primer extension for 39 distinct germline variants. The products were then sorted and analyzed using the Luminex xMAP system. Genotypes were compared with previously determined sequence data. In the Toronto training cohort, all 145 samples with known variants were detected by the bead assay (100% concordance). Analysis of the 598 samples from the GenoMEL validation set led to identification of 150/155 expected variants (96.77%). Overall, the bead assay correctly genotyped 1,540/1,603 (96.07%) of all individuals in the study and 1,540/1,545 (99.68%) of individuals whose variants were represented in the probe set. Out of a total of 62,517 allelic calls, 62,512 (99.99%) were correctly assigned. The multiplex bead-based assay is an accurate method for genotyping CDKN2A/CDK4 variants and is potentially useful in genotyping low-to-moderate melanoma risk single-nucleotide polymorphisms.     

BRAF polymorphisms and risk of melanocytic neoplasia

Somatic mutations of the BRAF gene are common in melanomas and nevi but the contribution of polymorphisms in this gene to melanoma or nevus susceptibility remains unclear. An Australian melanoma case-control sample was typed for 16 single nucleotide polymorphisms (SNP) within the BRAF gene, and five SNP in three neighboring genes. The sample comprised 755 melanoma cases from 740 families stratified by family history of melanoma and controls from 635 unselected twin families (2,239 individuals). Ancestry of the cases and controls was recorded, and the twins had undergone skin examination to assess total body nevus count, degree of freckling, and pigmentation phenotype. Genotyping was carried out via primer extension followed by matrix-assisted laser desorption ionization-time of flight mass spectrometry. SNP in the BRAF gene were found to be weakly associated with melanoma status but not with development of nevi or freckles. The estimated proportion of attributable risk of melanoma due to variants in BRAF is 1.6%. This study shows that BRAF polymorphisms predispose to melanoma but the causal variant has yet to be determined. The burden of disease associated with this variant is greater than that associated with the major melanoma susceptibility locus CDKN2A, which has an estimated attributable risk of 0.2%.     

Psoriasis and melanocytic naevi: does the first confer a protective role against melanocyte progression to naevi?

Background Some of the cytokines that have effects on melanogenesis are also reported to be involved in psoriasis. Objectives We therefore studied the relationship between psoriasis and melanocytic naevi. In particular, the aim of our study was to investigate the number of melanocytic naevi in patients with psoriasis vs. controls. Methods We performed a prospective case–control study, analysing 93 adult patients with psoriasis and 174 adult aged‐matched controls. For each participant a questionnaire was completed to establish personal data, personal medical history, and personal and familial history of skin cancer and psoriasis. We analysed interleukin (IL)‐1α, IL‐6 and tumour necrosis factor (TNF)‐α gene expression at the peripheral blood mononuclear cell level in patients with psoriasis and in controls. Results In our study, patients with psoriasis presented a lower number of areas with naevi in comparison with controls (P < 0·0001). Nobody had ever had squamous cell carcinoma or melanoma in the psoriatic group; moreover, there was a significant difference in familial history of melanoma between the two groups (none in the psoriatic group vs. 8% in the control group; P < 0·05). IL‐1α, IL‐6 and TNF‐α expression levels were higher in patients with psoriasis. Conclusions People with psoriasis had fewer melanocytic naevi. This suggests that the proinflammatory cytokine network in psoriasis skin might inhibit melanogenesis, melanocyte growth and/or progression to naevi.     

Role of glutathione S-transferases in melanoma susceptibility: association with GSTP1 rs1695 polymorphism

Background Glutathione S‐transferases (GSTs) GSTM1, GSTT1 and GSTP1 are multifunctional enzymes involved in the detoxification of a wide range of reactive oxygen species produced during melanin synthesis and oxidative stress processes. Objectives Single nucleotide polymorphisms (SNPs) in GSTP1 and copy number variants in GSTM1 and GSTT1 may be candidate low‐penetrance variants with a role in susceptibility to malignant melanoma (MM). Methods In this case–control study, 562 Spanish patients with sporadic MM and 338 cancer‐free control subjects were included, and the role of polymorphisms in these GST genes was investigated. Genotypes were established by quantitative real‐time polymerase chain reaction for GSTM1 and GSTT1 while TaqMan probes were used to genotype GSTP1 SNPs. Results The GSTP1 polymorphism rs1695, which encodes the amino acid change p.Ile105Val, was individually associated with MM [odds ratio (OR): 1·32, 95% confidence interval (CI): 1·06–1·63]. Furthermore, individuals carrying one or two MC1R nonsynonymous changes and GSTP1 rs1695 rare allele had an increased risk of developing MM (OR: 3·34, 95% CI: 1·42–8·09 and OR: 20·42, 95% CI: 2·80–417·42, respectively). Conclusions This is the first time that the GSTP1 rs1695 polymorphism is reported to be associated with MM. In addition, this study is one of the largest GST polymorphism studies undertaken in the Spanish population and the first time that copy number variants have been scrutinized in relation to MM.     

A pilot study of genetic variants in dopamine regulators with indoor tanning and melanoma

Many people frequently tan indoors despite being aware of the increased risk of melanoma. Ultraviolet radiation is hypothesized to modify biological reward pathways, for example, through the dopamine neurotransmitter system, to reinforce tanning behaviour. In this pilot study, we relied on questionnaire and DNA data from a recently completed case–control study to examine 67 single‐nucleotide polymorphisms (SNPs) and related haplotypes in five dopamine receptor and drug metabolism genes in relation to indoor tanning among controls. We also examined the association between individual SNPS and likelihood of melanoma, adjusting for or stratifying on indoor tanning status. In candidate and haplotype gene analyses, variants only in the DRD2 dopamine receptor and ANKK1 signalling genes were positively associated with indoor tanning use among controls; only associations for ANKK1 remained statistically significant (P < 0.05) after adjustment. Several SNPs in ANKK1 and DRD2 associated with indoor tanning among controls were also found to be associated with increased risk of melanoma. Upon stratifying for indoor tanning status, one ANKK1 SNP was positively associated with melanoma among non‐tanners, while three DRD2 SNPS were positively associated with melanoma among tanners or non‐tanners, depending on the SNP. These alleles represent important genomic regions to further explore addictive tanning behaviour.     

CDKN2A mutations in melanoma families from Uruguay

Background  Familial melanoma, a cluster of several cases within a single family, accounts for approximately 10% of cases of melanoma. Hereditary melanoma is defined as two or more first-degree relatives having melanoma. A member of a melanoma-prone family has a 35–70-fold increased relative risk of developing a melanoma. Genetic susceptibility is linked to the major susceptibility genes CDKN2A and CDK4 , and the minor susceptibility gene MC1R .
Objectives  To determine the clinical and genetic characteristics of cutaneous melanoma in melanoma-prone families from Uruguay.
Methods  We studied 13 individuals from six melanoma-prone families living in Uruguay. Phenotype, familial and personal history were recorded. Molecular screening of CDKN2A and CDK4 was done by polymerase chain reaction–single strand conformational polymorphism analysis. The MC1R gene was sequenced.
Results  Mutations in CDKN2A were detected in five of six families: c.−34G>T, p.G101W and p.E88X. A novel germline mutation p.E88X, associated with hereditary melanoma in two unrelated families, is described. We hypothesize that a founder effect occurred probably in the Mediterranean region. No mutations in CDK4 were detected. Six different MC1R variants, all previously reported, were present in Uruguayan families.
Conclusions  The overall rate of deleterious CDKN2A mutations in our familial melanoma pedigrees, even though the sample size is small, was considerably higher (83%) than the often quoted range.     

Assessment of tyrosinase variants and skin cancer risk in a large cohort of French subjects

Background

Tyrosinase (TYR) is a key pigmentation gene that is highly polymorphic and responsible for the most common form of autosomal recessive albinism, OCA1.

Objective

To assess the role of frequent and rare TYR variants in predisposition to skin cancer (SK) in the French population.

Methods

We genotyped a frequent TYR variant (p.R402Q) in 1273 patients {1047 cutaneous melanoma (CM) and 226 basal cell carcinoma (BCC)} and 925 controls, and the full coding region of TYR was sequenced in 287 patients suspected of genetic predisposition to SK (familial and/or multiple SK and/or onset before 40 years) and 187 controls.

Results

The homozygous p.R402Q variant was significantly associated with SK risk (P value = 0.008; OR = 1.57), and was mostly associated with multiple CM risk (P value = 0.021; OR = 2.50) and familial CM risk (P value = 0.022; OR = 2.16). In addition, 19 rare TYR variants, mainly albinism mutations, were identified in 15 patients and 8 controls. Among these, 3 clearly deleterious mutations (1 non-sense and 2 affecting mRNA splicing) were identified in 3 patients, one of which was homozygous.

Conclusion

Our data confirmed the association of TYR p.R402Q with SK risk in the French population, and support that rare deleterious TYR variants may also play a role in multi-factorial genetic predisposition to SK. These results should be confirmed by replications studies.     

Cutaneous hyperpigmentation and familial gastrointestinal stromal tumour associated with KIT mutation

Gastrointestinal stromal tumours (GISTs) are mesenchymal tumours arising in the gastrointestinal tract. Early detection, before metastasis occurs, is important as complete surgical excision achieves cure. Approximately 85% of GISTs are associated with mutations in the KIT gene, and although the majority of GISTs are sporadic, familial GISTs have been identified. Several families with multiple GIST tumours have also been described with various cutaneous findings including hyperpigmentation, multiple lentigines, vitiligo and urticaria pigmentosa. We discuss a 6‐year‐old boy who presented with an unusual pattern of hyperpigmentation in association with a family history of GIST. A causative KIT mutation was identified in DNA from the pigmented skin and from the resected GIST, and the patient was referred to the Paediatric Gastroenterology department for GIST screening. The term ‘GIST cutaneous hyperpigmentation disease’ has been suggested previously for the association of familial GIST with cutaneous hyperpigmentation caused by a germline KIT mutation.     

Comprehensive mutational analysis of CDKN2A and CDK4 in Greek patients with cutaneous melanoma

Background The penetrance of CDKN2A mutations is subject to geographical and latitudinal variation and is presumably dictated by ultraviolet radiation exposure and possibly other co‐inherited genetic factors. The frequency of mutations increases with the number of family members affected and the number of primary tumours, and also fluctuates with geography. To date, little is known about the prevalence of CDKN2A mutations in patients with melanoma from Greece. Objective To characterize the frequency of CDKN2A and CDK4 mutations in a hospital‐based population of Greek patients with melanoma. Methods Three hundred and four consecutive single primary melanoma (SPM), nine familial melanoma (FM) and seven multiple primary melanoma cases (MPM) were assessed for sequence variants in exons 1α, 1β and 2 of CDKN2A and exon 2 of CDK4. Results Germline CDKN2A mutations were detected in 10 of 304 SPM (3·3%), in four of seven MPM (57%) and in two of nine FM (22%) cases. The most common mutation was a Northern European allele (p16 p.R24P) detected in eight individuals. Five previously unreported CDKN2A variants were also identified: ?34G>C, c.41_43delins20bp, c.301G>C (p.G101R), c.301G>A (p.G101E) and c.296_297insGACC. We also describe the first report of a CDK4 p.R24H substitution in a Greek family. Conclusions The Greek population appears to harbour a higher prevalence of the CDKN2A mutation than other reported cohorts. This supports the notion that genetic susceptibility may play a stronger influence in a country with a relatively low incidence of melanoma. Furthermore, the identification of Northern European alleles suggests that gene migration may be responsible, in part, for the observed cases in Greece.     

Genetic analysis of three important genes in pigmentation and melanoma susceptibility: CDKN2A,MC1R and HERC2/OCA2

Please cite this paper as: Genetic analysis of three important genes in pigmentation and melanoma susceptibility: CDKN2A, MC1R and HERC2/OCA2. Experimental Dermatology 2010; 19 : 836–844. Abstract: The CDKN2A gene is regarded as the major familial malignant melanoma (MM) susceptibility gene. Human pigmentation is one of the main modulators of individual risk of developing MM. Therefore, the genes involved in the determination of skin colour and tanning response are potentially implicated in MM predisposition and may be useful predictors of MM risk in the general population. The human melanocortin‐1 receptor gene (MC1R) plays a crucial role in pigmentation and also appears to be important in MM. The OCA2 gene has emerged as a new and significant determinant of human iris colour variation. We present a case–control study in Spanish population including 390 consecutive patients with melanoma and 254 control subjects. Sequence analysis of the entire coding region and genotyping of 5 tag‐SNPs in the genomic region of MC1R was performed. We identified 27 variants, two reaching statistical significance [R160W (OR: 4.18, 95% CI: 1.24–14.04, P = 0.02) and D294H (OR: 3.10, 95% CI: 1.37–7.01, P = 0.01)] and we detected two novel non‐synonymous changes: V92L and T308M. Odds ratio for carrying two functional variants was 4.25 (95% CI: 2.30–7.84, P = 3.63 × 10^?6). Haplotypes of the entire MC1R region have been established, and we observed an enrichment of a rare European haplotype similar to African values carrying variants V92M and I155T. In addition, three potentially functional SNPs were selected in p16/CDKN2A and in the promoter region of OCA2/HERC2. Our data for CDKN2A gene did not reach statistically significant results for any of the two studied alleles. We found that the variant allele A > G of OCA2/HERC2 (rs12913832) was associated with pigmentation features: eye, hair and skin colour; P‐values = 1.8 × 10^?29, 9.2 × 10^?16, 1.1 × 10^?3, respectively, validating previous results.     

Risk of second primary in situ and invasive melanoma in a Dutch population‐based cohort: 1989–2008

Background Patients with melanoma are at increased risk of developing a subsequent melanoma. Objectives To estimate the risks of developing a second primary in situ or invasive cutaneous melanoma after a first melanoma, between 1989 and 2008. Methods Patients were followed until diagnosis of a second melanoma, date of death or end of study. Cumulative risks, standardized incidence ratio (SIR, observed second melanomas divided by background age‐, calendar‐ and sex‐specific incidence rates of melanoma, as recorded in the Netherlands Cancer Registry) and absolute excess risk (AER, observed minus expected per 10 000 person‐years) of second melanomas were calculated. Results In total, 10 765 patients with in situ melanoma and 46 700 with invasive melanoma were included. The cumulative risks of a second invasive melanoma after a first in situ or invasive melanoma at 20 years of follow‐up were 6·2% and 5·0%, respectively. The relative risk of developing any melanoma (in situ or invasive) after any first melanoma (measured as SIR) varied from 12·4‐fold [invasive after invasive melanoma; 95% confidence interval (CI) = 11·6–13·2] to 26·4‐fold (in situ after in situ melanoma; 95% CI = 22·6–30·7) increase compared with the general population. SIRs and AERs remained elevated up to 20 years after the first melanoma. Conclusions This study shows significantly increased long‐term risks (both relative and absolute) of developing a second invasive melanoma after a first melanoma (invasive and in situ), and might serve as a basis for follow‐up guidelines.     

Histological regression in primary melanoma: not a predictor of sentinel lymph node metastasis in a cohort of 397 patients

Background Regression has been proposed as a potential marker of dissemination in thin melanomas. Previous studies have shown conflicting results. Objective To determine if regression in melanoma is associated with an increased risk of sentinel lymph node (SLN) metastasis. Methods A cohort analysis was conducted. Data on all patients were collected on a standardized case report form during 10 years. A total of 397 consecutive patients with melanoma who underwent a SLN biopsy were analysed. All cases of melanoma and SLN biopsies were examined by the same two pathologists. Differences between melanomas with and without SLN metastasis were compared using Fisher’s exact test or the two‐sample t‐test and the χ² test. Multivariable logistic regression was used to adjust for possible confounding factors. Results We analysed 397 patients (411 melanomas) who underwent a SLN biopsy. The median Breslow index was 1·8 mm (interquartile range 1·1–3). Regression was observed in 23% (n = 94). SLN metastases were observed in 26% (n = 106). The frequency of SLN metastasis was 16% in melanomas with regression and 29% without regression (P = 0·012). The adjusted odds ratio (OR) for regressive melanoma was 0·9 [95% confidence interval (CI) 0·4–1·9; P = 0·777]. The risk of SLN metastasis was increased in melanoma cases with a Breslow index from 1·5 to < 2·0 mm (adjusted OR 3·1; 95% CI 1·4–7·1; P = 0·006) and ≥ 2·0 mm (adjusted OR 3·5; 95% CI 1·7–7·4; P = 0·001) and ulceration of the melanoma (adjusted OR 1·8; 95% CI 1·1–3·2; P = 0·03). Conclusion Regression is not an independent predictor of the risk of SLN metastasis in melanoma.     

POT1 germline mutations but not TERT promoter mutations are implicated in melanoma susceptibility in a large cohort of Spanish melanoma families

Melanoma is an aggressive type of skin cancer. Each year more than 250,000 new cases are diagnosed worldwide. If diagnosed at early stages, melanoma can be cured with relatively simple surgery. Globally, 20% of melanoma patients will die, but when diagnosed with thick (more advanced / later stage) tumours, the probability of dying increases by up to 60%. The best strategy to improve survival is with early diagnosis. The identification of people at risk is essential. Around 10% of cases occur in a familial context. This means that these individuals have an inherited genetic risk of developing melanoma explained by the presence of alterations (mutations) in specific genes. In a family with known mutation, healthy individuals who carry the mutation can be included in early detection programs that allow the diagnosis of melanomas at early stages. But the gene/genes responsible for this risk is still unknown in more than 70% of families. This study, from Spain, aimed to evaluate the prevalence of mutations in two genes (POT1 and TERT) in Spanish melanoma-prone families without known mutated genes. The authors sequenced (a way of studying) both genes in cases from 228 families. They found mutations in nearly 2% of the families assessed. They additionally identified two patients in two families who also had thyroid malignances. If this is confirmed in additional studies, the melanoma-prone families with mutations in this gene will also benefit from early diagnosis of thyroid tumours. No mutations were identified in TERT promoter indicating that this gene does not play an important role in familial melanoma susceptibility in Spain.     

Prevalence and distribution of melanocytic naevi on the scalp: a prospective study

Background Few studies have examined the incidence and characteristics of naevi on the scalp. Most studies of scalp naevi have been performed in children, whose incidence of scalp naevi is relatively high, at about 0·5–11·7% of the total body count of common naevi. Objectives To investigate the prevalence and distribution of scalp melanocytic naevi in patients of all ages. To our knowledge, ours is the first study to analyse in detail the relationships between melanocytic naevi on the scalp and total body naevi and total body atypical naevi. Methods We conducted a prospective study of patients visiting the dermatology outpatient clinic at the University of Florence, for examinations unrelated to the presence of naevi or melanoma. The study enrolled 795 subjects (417 females; 52·4%), with a median age of 35 years (range 4–80). Results The number of melanocytic naevi on the scalp increased significantly (r = 0·2057, P = 0·0008) as the number of total body melanocytic naevi increased and a correlation was found between the number of clinically atypical total body naevi and the number of scalp naevi. Relatively few naevi (15·5%) were located at the frontal region compared with other regions of the scalp, although the frontal region is more exposed to ultraviolet (UV) rays. Compared with subjects without alopecia, whose hair shields the scalp from UV rays, subjects with androgenetic alopecia showed no significant increase in number of scalp naevi. Conclusions Despite practical difficulties, early diagnostic screening for melanoma or screening during follow‐up examination for previous melanoma should involve examination of the entire skin surface, scalp included.