Changes in mouse epidermal DNA methylation during development of squamous cell carcinoma in response to UVR.

Squamous cell carcinoma (SCC) is a common skin cancer, often caused by exposure to ultraviolet radiation (UVR). Recent studies have shown that changes in DNA methylation play a crucial role in the development of cancers. However, methylation patterns of SCC are not well characterised. Identifying biomarkers for the risk of developing SCC could be helpful for early detection and diagnosis and can potentially improve treatment and prevention strategies. This study aimed to investigate methylation changes in the epidermis of mice exposed to UVR for 24 weeks. We examined the DNA methylation levels of 260 199 CpGs using the Illumina Infinium Mouse Methylation BeadChip and studied the epidermis of UVR-exposed and unexposed mice every 4 weeks for 24 weeks (n = 39). We identified CpGs with large differences in methylation levels (ß-values) between UVR-exposed and unexposed mice. We also observed differences in the epigenetic age of these mice. We identified CpGs in Rev, Ipmk, Rad51b, Fgfr2, Fgfr3 and Ctnnb1 that may serve as potential biomarkers for SCC risk and could be helpful for the early detection and prevention of SCC. Further investigations are necessary to determine the biological functions and clinical significance of these CpGs.

Biodistribution of iron oxide tattoo pigment: An experimental murine study.

Tattoo pigment is expected to migrate beyond the skin to regional lymph nodes and the liver. Modern tattoo ink commonly contains metals that may pose a clinical problem during MRI examinations. This study aimed to investigate the biodistribution of iron oxide pigment to internal organs in mice. Moreover, when exposed to a static magnetic field, we studied whether any reactions followed in the tattooed skin. Twenty-seven hairless C3.Cg-Hrhr/TifBomTac mice were included; 20 were tattooed with iron oxide ink in a rectangular 3 cm2 pattern; seven were controls. Ten of the tattooed mice were exposed to a 3 T MRI scanner's static magnetic field. Following euthanasia, evaluations of dissected organs involved MRI T2*-mapping, light microscopy (LM) and metal analysis. T2*-mapping measures the relaxation times of hydrogen nuclei in water and fat, which may be affected by neighbouring ferrimagnetic particles, thus enabling the detection of iron oxide particles in organs. Elemental analysis detected a significant level of metals in the tattooed skin compared to controls, but no skin reactions occurred when exposed to a 3 T static magnetic field. No disparity was observed in the liver samples with metal analysis. T2* mapping found no significant difference between the two groups. Only minute clusters of pigment particles were observed in the liver by LM. Our results demonstrate a minimal systemic distribution of the iron oxide pigments to the liver, whereas the kidney and brain were unaffected. The static magnetic field did not trigger skin reactions in magnetic tattoos but may induce image artefacts during MRI.

A personalised and systematically designed adherence intervention improves photoprotection in adults with Xeroderma Pigmentosum (XP): Results of the XPAND randomised controlled trial.

BACKGROUND: Poor adherence to photoprotection in Xeroderma Pigmentosum (XP) increases morbidity and shortens lifespan due to skin cancers. OBJECTIVE: To test a highly personalised intervention (XPAND) to reduce the dose of ultraviolet radiation (UVR) reaching the face in adults with XP, designed using known psychosocial determinants of poor photoprotection. METHODS: A two-arm parallel group randomised controlled trial, including patients with sub-optimal photoprotection to receive XPAND or a delayed intervention control arm that received XPAND the following year. XPAND comprises seven one-to-one sessions targeting photoprotection barriers (e.g., misconceptions about UVR) supported by personalised text messages, activity sheets, and educational materials incorporating behaviour change techniques. The primary outcome, mean daily UVR dose-to-face across 21 days in June-July 2018, was calculated by combining UVR exposure at the wrist with a face photoprotection activity diary. Secondary outcomes were UVR dose-to-face across 21 days in August 2018, time spent outside, photoprotective measures used outside, mood, automaticity, confidence-to-photoprotect. Financial costs and quality-adjusted life years (QALYs) were calculated. RESULTS: 16 patients were randomised, 13 provided sufficient data for primary outcome analysis. The XPAND group (n=8) had lower mean daily UVR dose-to-face [0.03 SED (SD 0.02] compared to control (n=7) [0.36 SED (SD 0.16)] (adjusted difference=-0.25, p<0.001, Hedge's g=2.2). No significant between-group differences were observed in time spent outside, photoprotection outside, mood, or confidence. The delayed intervention control showed improvements in UVR dose-to-face (adjusted difference=-0.05, Hedge's g=-0.1) , time outside (adjusted difference=-69.9, Hedge's g=-0.28), and photoprotection (adjusted difference=-0.23, Hedge's g=0.45), after receiving XPAND. XPAND was associated with lower treatment costs (£-2642; 95% CI: -£8715 to £3873) and fewer QALYs (-0.0141; 95% CI: -0.0369 to 0.0028). CONCLUSIONS: XPAND was associated with a lower UVR dose-to-face in XP patients and was cost-effective.

Urinary thymidine dimer excretion reflects personal ultraviolet radiation exposure levels.

Exposure to ultraviolet radiation (UVR) leads to skin DNA damage, specifically in the form of cyclobutane pyrimidine dimers, with thymidine dimers being the most common. Quantifying these dimers can indicate the extent of DNA damage resulting from UVR exposure. Here, a new liquid chromatography-mass spectrometry (LC-MS) method was used to quantify thymidine dimers in the urine after a temporary increase in real-life UVR exposure. Healthy Danish volunteers (n = 27) experienced increased UVR exposure during a winter vacation. Individual exposure, assessed via personally worn electronic UVR dosimeters, revealed a mean exposure level of 32.9 standard erythema doses (SEDs) during the last week of vacation. Morning urine thymidine dimer concentrations were markedly elevated both 1 and 2 days post-vacation, and individual thymidine dimer levels correlated with UVR exposure during the last week of the vacation. The strongest correlation with erythema-weighted personal UVR exposure (Power model, r2 = 0.64, p < 0.001) was observed when both morning urine samples were combined to measure 48-h thymidine dimer excretion, whereas 24-h excretion based on a single sample provided a weaker correlation (Power model, r2 = 0.55, p < 0.001). Sex, age, and skin phototype had no significant effect on these correlations. For the first time, urinary thymidine dimer excretion was quantified by LC-MS to evaluate the effect of a temporary increase in personal UVR exposure in a real-life setting. The high sensitivity to elevated UVR exposure and correlation between urinary excretion and measured SED suggest that this approach may be used to quantify DNA damage and repair and to evaluate photoprevention strategies.

A European Consensus on the Consistent Use of the Term "Keratinocyte Cancer".

Keratinocyte-derived skin cancers comprise basal cell carcinoma, squamous cell carcinoma, its precursor actinic keratosis, and Bowen's disease. Historically, this group of neoplasms has been subsumed under the term non-melanoma skin cancer. However, the term non-melanoma skin cancer can be misleading and lacks precision. Therefore, more precise and reasonable terminology, valuing the relevance of keratinocyte-derived cancer, appears pertinent to meet its clinical and scientific significance. A group of experienced dermato-oncologists initiated a consensus approach to promote the use of the term "keratinocyte cancer" instead of "non-melanoma skin cancer" when referring to carcinomas and their precursors that are derived from keratinocytes. The vote among members of the consensus group indicated unanimous agreement on the consistent use of the term "keratinocyte cancer" instead of "non-melanoma skin cancer". International delegates also voted in favour of the revised terminology. The more precise and, by means of etiopathogenesis, correct term "keratinocyte cancer" should be consistently used for malignancies originated from keratinocytes. This is expected to have a positive impact on patient-physician communication and gives better justice to this important group of keratinocyte-derived cancers.

A revised action spectrum for vitamin D synthesis by suberythemal UV radiation exposure in humans in vivo.

Action spectra are important biological weighting functions for risk/benefit analyses of ultraviolet (UV) radiation (UVR) exposure. One important human benefit of exposure to terrestrial solar UVB radiation (∼295 to 315 nm) is the cutaneous synthesis of vitamin D3 that is initiated by the photoconversion of 7-dehydrocholesterol to previtamin D3 An action spectrum for this process that is followed by other nonphotochemical steps to achieve biologically active vitamin D3 has been established from ex vivo data and is widely used, although its validity has been questioned. We tested this action spectrum in vivo by full- or partial-body suberythemal irradiation of 75 healthy young volunteers with five different polychromatic UVR spectra on five serial occasions. Serum 25-hydroxyvitamin D3 [25(OH)D3] levels, as the most accurate measure of vitamin D3 status, were assessed before, during, and after the exposures. These were then used to generate linear dose-response curves that were different for each UVR spectrum. It was established that the previtamin D3 action spectrum was not valid when related to the serum 25(OH)D3 levels, as weighting the UVR doses with this action spectrum did not result in a common regression line unless it was adjusted by a blue shift, with 5 nm giving the best fit. Such a blue shift is in accord with the published in vitro action spectra for vitamin D3 synthesis. Thus, calculations regarding the risk (typically erythema) versus the benefit of exposure to solar UVR based on the ex vivo previtamin D3 action spectrum require revision.

Phototesting in erythropoietic protoporphyria trials: A systematic review.

Severe skin pain when exposed to long wave ultraviolet radiation or visible light is the main symptom of erythropoietic protoporphyria (EPP). Treatment options for EPP are inadequate and new treatments are needed but hampered by the lack of valid efficacy outcomes. Phototesting with well-defined illumination of the skin can be performed reliably. We aimed to provide an overview of phototest procedures used to evaluate EPP treatments. Systematic searches of Embase, MEDLINE and the Cochrane Library were performed. Searches identified 11 studies using photosensitivity as efficacy outcome. The studies used eight different phototest protocols. Illuminations were performed with a filtered high-pressure mercury arc, or a xenon arc lamp equipped with monochromator or filters. Some used broadband, others narrowband illumination. In all protocols phototests were performed on the hands or the back. Endpoints were minimal dose required to induce either first symptom of discomfort, erythema, urticaria or intolerable pain. Other endpoints were change in erythema intensity or diameter of any type of flare after exposure compared to before. In conclusion, protocols displayed extensive variability in illumination set-up and evaluation of phototest reactions. Implementation of a standardized phototest method will allow more consistent and reliable outcome evaluation in future therapeutic research of protoporphyric photosensitivity.

Does systemic hydrochlorothiazide increase the risk of developing ultraviolet radiation-induced skin tumours in hairless mice?

Hydrochlorothiazide (HCTZ) is a frequently prescribed diuretic that exhibits photosensitizing properties. It is used to treat hypertension and edema. Dermato-epidemiological studies in various populations have linked HCTZ treatment with increased risk of particular types of skin cancer, including malignant melanoma (lentigo subtype), and both basal cell carcinoma and squamous cell carcinoma (SCC). This study investigated whether either of two different doses of HCTZ increased the risk of SCC development in mice exposed to ultraviolet radiation (UVR). A total of three groups of hairless mice were used in this study (total, N = 71). One group received a low dose (0.26 mg/mouse/day) and another group received a high dose (0.52 mg/mouse/day) of HCTZ in their drinking water; a third UVR control group received only tap water. All three groups were irradiated with UVR until the mice developed three tumours that were 4 mm in size. The times to SCC tumour development were recorded. In the low-dose group, the median time to develop an SCC tumour was 170 days; in both the high-dose group and the control group, the median time to develop anexd SCC tumour was 163 days (p ≥ 0.331). In our hairless mouse model, we found that mice treated with UVR plus HCTZ did not develop SCCs more rapidly than mice treated with UVR but not HCTZ.

Equipment developed for simplifying routine phototesting in dermatology.

Some people react abnormally when exposed to sunlight by getting easily burned or develop a rash. When testing a patient's level of photosensitivity in the clinic, the UVR dose to provoke erythema is determined by the minimal erythema dose (MED) test. Subsequently, a photoprovocation test is performed to detect abnormal skin reactions by daily exposing the skin to UVR for several consecutive days. Associated problems in MED testing include choice of an even skin area for testing, patients keeping still during the test, testing with different UVR doses simultaneously, and securing clear borders of erythema. To address these issues, a MED Test Patch was developed which adheres closely to the skin to ensure sharp erythema borders and provides six irradiation fields with decremental doses of 20%. For MED testing, we constructed a solar simulator and LED lamps with peak emissions at 309 and 370 nm, small enough to be mounted directly on to the MED Test Patch and accommodate patient movements. These lamps and a 415 nm LED can also be used for provocation testing which is best performed on the back where the skin is assumed to have identical UVR sensitivity, and the area is large enough for adjacent MED and provocation test fields. Reading of erythema is still performed by visual and tactile evaluation. The UVA and UVB MED test can be performed in 1 h. The advantage of these developments is an easy-to-use, standardized test method with improved accuracy of the results.

RNA analysis of tape strips to rule out melanoma in lesions clinically assessed as cutaneous malignant melanoma: A diagnostic study.

BACKGROUND: Distinguishing cutaneous malignant melanoma (CMM) from nevi can be clinically challenging. Suspicious lesions are therefore excised, resulting in many benign lesions being removed surgically to find 1 CMM. It has been proposed to use tape strip derived ribonucleic acid (RNA) to distinguish CMM from nevi. OBJECTIVE: To develop this technique further and validate if RNA profiles can rule out CMM in clinically suspicious lesions with 100% sensitivity. METHODS: Before surgical excision, 200 lesions clinically assessed as CMM were tape stripped. Expression levels of 11 genes on the tapes were investigated by RNA measurement and used in a rule-out test. RESULTS: Histopathology showed that 73 CMMs and 127 non-CMMs were included. Our test correctly identified all CMMs (100% sensitivity) based on the expression levels of 2 oncogenes, PRAME and KIT, relative to a housekeeping gene. Patient age and sample storage time were also significant. Simultaneously, our test correctly excluded CMM in 32% of non-CMM lesions (32% specificity). LIMITATIONS: Our sample contained a very high proportion of CMMs, perhaps due to inclusion during COVID-19 shutdown. Validation in a separate trial must be performed. CONCLUSION: Our results demonstrate that the technique can reduce removal of benign lesions by one-third without overlooking any CMMs.

Identifying the psychosocial predictors of ultraviolet exposure to the face in patients with xeroderma pigmentosum: a study of the behavioural factors affecting clinical outcomes in this genetic disease.

BACKGROUND: For patients with xeroderma pigmentosum (XP), the main means of preventing skin and eye cancers is extreme protection against ultraviolet radiation (UVR), particularly for the face. We have recently developed a methodology for objectively measuring photoprotection behaviour ('UVR dose to facial skin') and have found that the degree of photoprotection varies greatly between patients with XP. We have previously identified factors affecting photoprotection behaviour in XP using a subjective measure of photoprotection. Here, we have used this objective methodology to identify the factors which determine photoprotection behaviour in XP. METHODS: We studied 29 psychological, social, demographic and clinical variables in 36 patients with XP. We have previously objectively measured UVR protection (by measuring the dose of UVR reaching the skin of the face over a 3-week period) in these patients. Here, we use linear mixed-effects model analysis to identify the factors which lead to the differences in degree of photoprotection observed in these patients. RESULTS: Psychosocial factors accounted for as much of the interindividual variation in photoprotection behaviour (29%) as demographic and clinical factors (24%). Psychosocial factors significantly associated with worse UVR protection included: automaticity of the behaviours, and a group of beliefs and perceptions about XP and photoprotection known to associate with poor treatment adherence in other diseases. CONCLUSIONS: We have identified factors contributing to poor photoprotection in XP. Identifying these potentially reversible psychosocial features has enabled us to design an intervention to improve photoprotection in patients with XP, aiming to prevent skin and eye cancers in these patients.

Low vitamin D in dark-skinned immigrants is mainly due to clothing habits and low UVR exposure: a Danish observational study.

Low 25-hydroxyvitamin D3 (25(OH)D) among dark-pigmented persons has been observed. To elucidate the reason for this we examined sun behaviour, sun-exposed body area, solar UVR exposure and 25(OH)D levels in immigrants with dark pigmented skin and Danes with light pigmented skin. Clothing, sun behaviour, and diet were recorded daily during a Danish summer season (93 analysed days). Erythema-weighted UVR doses were measured by personal electronic UVR dosimeters (with erythema response, measurement every 5th second) and 25(OH)D was measured in 72 participants (33 dark-skinned and 39 light-skinned). The immigrants exposed 28% less skin area, received 70% less UVR dose, and had 71% less 25(OH)D increase during the summer. The UVR reactivity (Δ25(OH)D per joule accumulated UVR dose) was similar (P = 0.62) among the immigrants (0.53 nmol l-1 J-1) and the Danes (0.63 nmol l-1 J-1). In the groups combined, 25(OH)D levels after summer were mainly influenced by UVR dose to exposed skin (28.8%) and 25(OH)D start level (27.9%). Height and measured constitutive skin pigmentation were of minor influence: 3.5% and 3.2%, respectively. Sun exposure and clothing habits were the main reasons for lower 25(OH)D level after summer in the darker immigrants, as both groups had similar UVR reactivity.

Few X-ray and PUVA treatments accelerate photocarcinogenesis in hairless mice.

PUVA is a treatment that combines oral methoxypsoralen (8-MOP) with ultraviolet radiation A (UVA). It is used for severe psoriasis and the early stages of T-cell lymphoma. X-rays are an effective treatment for skin cancers. Both treatments are in higher doses used to treat skin malignancies and simultaneously increase the risk of keratinocyte cancer. The main objective of this study was to test whether a few PUVA or X-ray treatments could delay the development of ultraviolet radiation (UVR)-induced skin tumors in a well-established hairless mouse model. Three groups of immunocompetent mice (total, N = 75) were included in the study. All groups were UVR-exposed during the study period. In addition, one group was treated with PUVA and another group was treated with X-rays at days 45, 52, 90 and 97. A control group was treated with UVR only. We recorded when the first, second and third skin tumors were induced in each mouse. Skin tumors developed significantly earlier in both the PUVA and X-ray groups (median, 188 days) than in the control mice (median, 215 days; p < 0.001). Therefore, a few X-ray and PUVA treatments both significantly accelerated the development of skin tumors in hairless mice, compared to UVR controls. Neither treatment showed a delay of UVR-induced skin tumors and caution should be exercised before applying these treatments to sun-damaged skin.

Measurements of sun sensitivity in five European countries confirm the relative nature of Fitzpatrick skin phototype scale.

BACKGROUND/PURPOSE: Skin colour and sun sensitivity are highly related to the distance to the equator: people in southern latitudes are usually darker and less sensitive to sun than in northern latitudes. Whether differences in sun sensitivity can be found in a relatively homogenous European population is unclear. We aimed to objectively measure sun sensitivity (assessed as pigment protection factor (PPF)) in five European countries, relate it to self-assessed Fitzpatrick skin phototype (FST) and to determine whether PPF levels in the different FST categories are dependent on the investigated countries. METHODS: Volunteers (n = 569) were recruited in Copenhagen (Denmark), Dublin (Ireland), London (England), Münster (Germany) and Ioannina (Greece). Skin phototype was self-assessed using the FST scale. PPF was measured at both sun-protected buttocks and five sun-exposed skin sites by a skin reflectance spectrophotometer. RESULTS: Overall, there were statistically significant differences in PPF of the buttocks, inner arm, outer arm, forehead, chest and back between the five countries (P ≤ .031). Generally, PPF level was lower in northern than in southern latitudes. PPF of the buttocks was similar in all countries for those who identified as FST I (P = .723). However, it was statistically significantly different (P ≤ 2.913*10-4 ) and country-dependent for those who identified as FST II-IV. CONCLUSION: Objectively measured sun sensitivity is higher (lower PPF) in northern compared with southern latitudes. The choice of self-identified FST category is influenced by a person's immediate environment. Therefore, we confirmed the relative nature of the FST scale and the need to standardise the skin phototype assessment procedure.

A Handful of Sunscreen for Whole-Body Application.

BACKGROUND: The rule of thumb "Fill up a handful of sunscreen and spread it all over your body" has been used in several sun safety campaigns. The intention was to increase the applied sunscreen to obtain a quantity of 2 mg/cm2 to all accessible skin. The present study is the first to investigate how this advice works in practice, evaluated by quantity of sunscreen applied and amount of covered skin. METHODS: Seventeen volunteers wearing swimwear were asked to "Fill up a handful and spread it all over your body." Before and after sunscreen application, the volunteers were photographed in black light. As sunscreen absorbs black light, the darkness of the skin increases with increasing amounts of applied sunscreen, making it possible to identify skin left without coverage. The sunscreen container was weighed before and after to quantify the amount of sunscreen applied. RESULTS: A median of 21% of the accessible skin was left completely without coverage. The 79% covered area was covered with a median of 1.12 mg/cm2, not the expected 2 mg/cm2. CONCLUSION: In practice, the advice "Fill up a handful of sunscreen and spread it all over your body" led to a better but still modest protection, compared to the intended effect.

Personal electronic UVR dosimeter measurements: specific and general uncertainties.

Personal ultraviolet radiation (UVR) dosimetry has been performed for decades to objectively measure human exposure to UVR. These measurements have been used to investigate solar behaviour and its negative effects on human health such as skin cancer and positive effects such as vitamin D formation. A specific electronic dosimeter is described with a spectral sensitivity as the erythema response for human skin and temperature measurements for compliance control. Technical, methodological and environmental causes of uncertainties regarding personal UV dosimetry are investigated using this dosimeter as an example, which enables us to show the dosimeter's limitations and enables readers to compare their dosimeters with that described and to increase awareness of imperfections of dosimeters. The dosimeter's spectral response, cosine response, linearity, temperature dependency and sensitivity are investigated. As opposed to biological and chemical dosimeters, electronic dosimeters do not measure UV radiation continuously but at time-intervals (sampling). The error introduced by sampling is investigated for sampling intervals from 1 second up to 60 seconds for 3 groups of people (n = 18, 1.1-4.6 hours of positive UV measurements) on sunny (n = 12) and cloudy (n = 6) days. Increasing the sample time by 1 second added on average an uncertainty of maximum +0.29% to -0.27% per added second compared to the 1-second sample time. The importance of dirt on the sensor was investigated in 24 dosimeters after 6 months use by farmers. The reduction in the registered dose due to the dirty sensor was 2.3% (median = 2.0%, inter-quartile range = 2.0%, max = 5%) suggesting that dirt on the sensor generally does not play a significant role.

Adult UVR exposure changes with life stage - a 14-year follow-up study using personal electronic UVR dosimeters.

Over a period spanning 14 years (1999-2001, 2006 and 2012), 31 volunteers participated in sun behaviour studies with the same protocol wearing a personal, electronic wrist-borne UVR dosimeter and completed sun exposure diaries resulting in a total of 15 946 measurements days (126 days per person per year). The participants individually maintained their UVR dose level and behaviour over the years. No statistically significant differences were seen from year to year in the "estimated annual UVR dose", the "mean UVR dose per day", the "mean percentage of ambient UVR", "days sunbathing to get a tan", "days with intermittent exposure" or in "sunburn episodes". The 20 participants still active in the labour market used sunscreen on more days in 2012 than in 1999 (p = 0.019) and with a significantly higher SPF (sun protecting factor (p < 0.001)) resulting in significantly fewer days with risk behaviour without sunscreen applied in 2012 than in 2006 (p < 0.001) and 1999 (p < 0.003). This was in contrast to the 11 participants who retired during the study period. The retired group received a non-significant 45% higher UV dose in 2012 than in 1999 (p = 0.054). In an additional study, nine 30-year-old indoor workers (high school students in the 1999 study) had changed their sun exposure pattern and had fewer days sunbathing (p = 0.008) and fewer risk behaviour days without sunscreen applied in 2012 than in 1999 (p = 0.002). Conclusion: The participants still active in the labour market maintained their sun exposure behaviour over a 14-year period. The retirees had a higher UVR dose and riskier exposure behaviour after retirement, while the high school students had changed to less risky sun behaviour on becoming indoor workers.

Pigment genes not skin pigmentation affect UVB-induced vitamin D.

Skin pigmentation is believed to contribute to the generally low serum 25-hydroxyvitamin D (25(OH)D) concentrations observed in darker-skinned persons. The influence of measured skin pigmentation on UVB-induced 25(OH)D increase was investigated together with 9 demographic and 13 genetic parameters (pigment SNPs). Forty participants representing a wide range in measured skin pigmentation were exposed to identical UVB doses on identical body areas over nine weeks with weekly measurements of serum 25(OH)D. This study took place in Denmark during winter, a period with negligible ambient UVB, so variation in 25(OH)D synthesis was not influenced by latitude, season, sun and clothing habits. The increase in 25(OH)D concentration displayed considerable variation (range: 2.9 to 139 nmol L-1). Constitutive and facultative skin pigmentation exerted separate influence on the variation of the UVB-induced linear 25(OH)D increase. However, this influence was statistically non-significant in the presence of separate significant pigment SNPs. The variation in the 25(OH)D increase in the combined linear model was not explained by measured skin pigmentation but by sex, height, age and seven SNPs located in the ASIP, MTAP, MIR196A29 and Solute Carrier Family genes. This linear model including individual intercepts and the 10 parameters influencing the slope explained 77.4% of the variation. This study confirmed the influence of sex, age and height on 25(OH)D increase and found that pigment genes provided a better relation to UVB-induced 25(OH)D increase compared to the actual measured skin pigmentation. Therefore, only investigating skin pigmentation obscures other causal parameters for low 25(OH)D.

Skin cancer phototype: A new classification directly related to skin cancer and based on responses from 2869 individuals.

BACKGROUND/PURPOSE: Fitzpatrick phototype (FST) classification (based on ability to tan and tendency to burn) is widely used for evaluating skin cancer risk; however, it was not developed for that purpose and has been criticised scientifically. The purpose of the present study was a first approach in establishing a new skin cancer phototype (SCP) classification with direct relation to skin cancer risk, based on the questions originally proposed by Fitzpatrick. However, contrary to Fitzpatrick, the questions are in the present study kept separate. METHODS: Validated information on skin cancer and answers about participants' tendency to burn (4 answers) and ability to tan (4 answers) were obtained from 2869 Danes. The 16 (4 × 4 answers) possible answers formed a matrix, on which a logistic regression was carried out. Successively, the matrix neighbours which were insignificantly different were identified; of which the neighbours with the mutual lowest difference were merged. The merging resulted in four different SCP classes. RESULTS: There was a linear relationship between SCP classes and skin cancer risk. Further, SCP was as good a predictor of skin cancer as objectively measured skin phototype. CONCLUSION: As skin phototype is an important factor in skin cancer research, SCP has great potential in investigative studies of skin cancer risk.

Visual scales are superior to questionnaires in skin phototype self-assessment by children.

BACKGROUND/PURPOSE: There are no suitable methods for skin phototype self-assessment by children. Our study investigated several skin phototype self-assessment methods in children to identify the best correlation to objectively measure skin phototype. METHODS: Danish schoolchildren (ages 6-19) participated in a nation-wide study that assessed skin, eye, hair colour and sun behaviour. Skin phototype self-assessment was performed by children using two visual colour scales (cartoon faces and colour cards), question-based colour scale and questions about tendency to burn and ability to tan. For objective skin phototype measurements, 483 children from all age groups were selected and their pigment protection factor (PPF) was measured at three skin sites using a skin reflectance spectrophotometer. RESULTS: Cartoon faces (r2  = 0.654) and colour cards (r2  = 0.659) were better at predicting PPF on the inner forearm than the question-based colour method (r2  = 0.520). PPF prediction from questions on skin reaction to sun exposure was markedly inferior (r2  ≤ 0.142) to both visual colour scales and question-based colour method. CONCLUSION: Both visual colour scales proved to be superior to question-based skin phototype self-assessment in schoolchildren. In contrast, questions on skin reaction to sun exposure were shown to be an unsuitable tool for self-assessment of skin phototype in children.