The Genetics of Sun Sensitivity in Humans

Humans vary >100-fold in their sensitivity to the harmful effects of ultraviolet radiation. The main determinants of sensitivity are melanin pigmentation and less-well-characterized differences in skin inflammation and repair processes. Pigmentation has a high heritability, but susceptibility to cancers of the skin, a key marker of sun sensitivity, is less heritable. Despite a large number of murine coat-color mutations, only one gene in humans, the melanocortin 1 receptor (MC1R), is known to account for substantial variation in skin and hair color and in skin cancer incidence. MC1R encodes a 317–amino acid G-coupled receptor that controls the relative amounts of the two major melanin classes, eumelanin and pheomelanin. Most persons with red hair are homozygous for alleles of the MC1R gene that show varying degrees of diminished function. More than 65 human MC1R alleles with nonsynonymous changes have been identified, and current evidence suggests that many of them vary in their physiological activity, such that a graded series of responses can be achieved on the basis of (i) dosage effects (of one or two alleles) and (ii) individual differences in the pharmacological profile in response to ligand. Thus, a single locus, identified within a Mendelian framework, can contribute significantly to human pigmentary variation

Dermatology undergraduate skin cancer training: a disconnect between recommendations, clinical exposure and competence

<p>Abstract</p> <p>Background</p> <p>Skin cancers are the most common malignancies in Caucasian populations. Non-specialists are responsible for the initial assessment of skin lesions and are required to act as the gatekeepers to dermatological cancer services in many healthcare systems. The majority of such physicians receive very limited formal undergraduate or postgraduate dermatology training. The British Association of Dermatologists (BAD) has produced guidelines that list the lesions that students should be able to diagnose on graduation and the majority of UK medical schools’ operate curricula in keeping with these. There is, however, virtually no evidence as to whether these competencies are being achieved. We set out to determine students’ competence at skin lesion diagnosis and to quantify their clinical exposure to examples of such lesions during their dermatology attachment.</p> <p>Methods</p> <p>Three linked studies were undertaken. In the first, students’ competence was tested by randomized slideshows of images containing the 16 lesions recommended in the UK guidelines. Students’ accuracy was tested at the beginning (Day 1) and end (Day 10) of their clinical placement, with a random sample of students retested 12 months later. Secondly, students’ exposure to these lesions was recorded during their attachments. Finally a survey of the additional dermatological resources used by the students was undertaken.</p> <p>Results</p> <p>Study 1: Students’ diagnostic accuracy increased from 11% on Day 1 to 33% on Day 10 (effect size +2.72). After 12 months half of this effect had disappeared and the students accuracy had dropped to 24%. Study 2: Students’ exposure to the recommended lesions was poor with 82% not even witnessing a single example of each of the 3 major skin cancers. Despite these measurements, only a minority of students reported that they were not confident at diagnosing skin tumours. Study 3: The majority of students use additional resources to supplement their learning.</p> <p>Conclusions</p> <p>In the light of what we know about learning in dermatology, our data would suggest, that the current (traditional) undergraduate attachment is inadequate to meet the UK recommendations for graduate competence. As well as critically examining the basis for these recommendations, we need more empirical data on student performance and exposure, in order to improve teaching and learning.</p

Low Frequency of Loss and Heterozygosity At the Nevoid Basal Cell Carcinoma Locus and Other Selected Loci in Appendageal Tumors

Previous studies of loss of heterozygosity (LOH) have revealed distinct patterns of allelic loss in some skin tumors. In basal cell carcinomas (BCCs) loss of heterozygosity is virtually restricted to chromosome 9, whereas in squamous cell carcinomas (SCCs) and actinic keratoses loss is more widespread involving chromosomes 3, 9, 13, and 17. Because there are histological similarities between BCCs and some appendageal tumors, and because some lines of evidence suggest that BCCs are appendageal in origin, we carried out a limited allelotype in 41 appendageal tumors. The overall frequency of allelic loss was low (4 out of 247 informative loci; 1.6%). LOH was seen in a proliferating trichilemmal cyst (l7p), a sebaceous epithelioma (l7q), an eccrine porocarcinoma (17q), a trichoepithelioma (9q), and in two basal cell carcinomas showing eccrine or granular cell differentiation that were originally misdiagnosed (9q). The pattern of loss in this mixed group of appendageal tumors shows differences from both BCCs and SCCs, and further emphasizes the unique genetic profile and behavior of BCCs. The finding of 9q loss in BCCs with eccrine or granular cell differentiation shows that 9q loss occurs in different histological subtypes of BCCs

Melanoma: What are the gaps in our knowledge?

Jonathan Rees outlines a number of puzzling gaps that remain in our knowledge of the etiology of non-acral melanomas

Are Subjective Accounts of Itch to be Relied on? The Lack of Relation Between Visual Analogue Itch Scores and Actigraphic Measures of Scratch

There is a widespread belief that subjective accounts of disease are key components of measures of disease severity and quality of life. In the present study we have set out to test this hypothesis using visual analogue scales (VAS) for itch, as a subjective measure, and actigraphy as an objective measure. One-hundred and seventeen itchy children and adults (and 25 controls) were studied for clusters of nights (total number 1,654) and actigraphy scores and VAS itch taken daily. Fifty-six percent of the night-to-night variation in actigraphy scores occurred between different individuals, while 44% was intra-subject. Neither age nor sex (children’s or adults’) predicted actigraphy scores, and the only significant predictor of actigraphy score was disease type (p = 0.001, r(2) = 0.51). In a multivariate model VAS itch score was not a significant determinant of actigraphy scores for either children or adults (p = 0.26). In order to see if there was a relation between VAS itch and actigraphy within the same patients (rather than between patients), 20 eczema patients wore the actigraph and scored VAS itch nightly for 42 nights. Little relationship was found between the actigraphy score and the VAS itch. Empirical autocorrelation analysis of VAS itch and actigraphy score reveal a clear autocorrelation for subjective VAS scores that was not found for the objective actigraphy score. Our data suggest a dissociation between scratch and perceived or recalled itch. One explanation is that VAS itch scores suffer from considerable anchoring, and context bias, and that their use in measures of disease severity is problematic