Development and characterisation of an irradiation device for biomedical studies covering the solar spectrum with individual regulated spectral bands.

To understand the importance of terrestrial solar exposure on human skin, not only individual spectral components need to be considered in biomedical studies, but also the relevance of the combined action profile of the complete solar spectrum (cSS) must be established. We therefore developed a novel irradiation device that combines the emission of four individual lamps (UVB, UVA, VIS and nIR) to achieve exposure from 280 to 1400 nm with individual controllable lamps. The integrated irradiance of each spectral band is similar to the solar spectrum. The lamps can be utilised individually or in any desired combination. Here we present the design, realisation, and validation of this irradiation device as well as biological results on cellular metabolism (MTT assay), cell cycle alterations, and clonogenic growth in HaCaT cells after exposures to the individual spectral bands as well as their simultaneous combinations. Thereby, we demonstrate that UVB combined with UVA is the main determinant for the metabolic activity within cSS. Also, UVB-dependent effects dominate cell cycle regulation in cSS, whilst UVA and nIR have little influence. Lastly, also clonogenic growth is dominated by the UVB action profile in cSS, despite nIR showing modulatory activity when applied in combination with UVB. Together, this highlights the regulatory influence of the different spectral bands on the three biological endpoints and demonstrates their modulation when being part of the complete solar spectrum.

Does sunscreen use comply with official recommendations? Results of a nationwide survey in Germany.

BACKGROUND: The use of sunscreen can reduce the risk of UV-induced skin lesions. Health authorities have provided recommendations for the correct use of sunscreen use: Sufficient amount of sunscreen should be applied at least 30 min before the sun exposure and should be reapplied every 2 h. OBJECTIVE: We aimed to research the practice of sunscreen use in a population-based and representative sample in Germany. METHODS: For this cross-sectional survey, 3000 German residents aged 14-45 years were surveyed in standardized telephone interviews in 2018. Survey participants provided data on the frequency of sunscreen use in summer, timing of (re-)application and their skin characteristics. The data were weighted by age, sex, educational level and federal state to ensure the national representativeness of the sample. RESULTS: Overall, 79.4% of respondents used sunscreen always, often or sometimes when being exposed to the sun. However, 87.2% of sunscreen users did not follow the recommendations on timing of application, 59.5% did not comply with the timing of reapplication. We also saw, that people potentially used too little sunscreen. These data did not differ noticeably by skin types of participants. CONCLUSION: Our study revealed deficits in use of sunscreen in Germany, indicating that people here pay little attention to the recommendations of health authorities, regardless of their skin type. There is therefore an urgent need for targeted public information on this issue. Improving public knowledge on correct sunscreen use through educational campaigns or individual counselling by health professionals could be a first step.

Epidemiological evidence of carcinogenicity of sunbed use and of efficacy of preventive measures.

The International Agency for Research on Cancer classified, in July 2009, exposure to artificial tanning devices (sunbeds) as carcinogenic to humans. This classification was based on evidence from epidemiological and experimental animal studies. The present chapter will review these epidemiological evidences. The summary risk estimates from 27 epidemiological studies obtained through a meta-analysis showed an increased risk of melanoma: summary relative risk (SRR) = 1.20 [95% confidence interval (CI) 1.08-1.34]. The risk was higher when exposure took place at younger age (SRR = 1.59; 95% CI 1.36-1.85). The risk was independent of skin sensitivity or population and a dose response was evident. A meta-analysis of 12 studies was conducted for non-melanoma skin cancers and showed a significantly increased risk for basal cell carcinoma (SRR = 1.29; 95% CI 1.08-1.53) and for squamous cell carcinoma (SRR = 1.67; 95% CI 1.29-2.17). As for melanoma, the risk for other skin cancers increased for first exposures at young age. Epidemiological studies have gradually strengthened the evidence for a causal relationship between indoor tanning and skin cancer and they fit with prior knowledge on relationship between UV exposure and skin cancer. Additionally, several case-control studies provided consistent evidence of a positive association between use of sunbed and ocular melanoma, also with greater risk for first exposures at younger age. Preventive measures based on information on risk or by requiring parental authorization for young users proved to be inefficient in several studies. The significant impact of strong actions or total ban, such as performed in Iceland, or a total ban of sunbed use, as in Brazil or Australian states, needs to be further assessed.

Decreasing sunbed use in the German population between 2001 and 2015: survey in 155 679 working persons.

BACKGROUND: UV radiation is a proven cause of skin cancer. Use of sunbeds has been shown to provide an attributable risk. OBJECTIVE: To evaluate the proportion of regular sunbed use in Germany based on large-scale population-based surveys over 15 years. METHODS: Skin cancer screenings by dermatologists were conducted between 2001 and 2015 in more than 500 German companies, including a clinical examination and interviews on the risk behaviour related to sunburns and sunbeds. RESULTS: Among 155 679 persons included regular sunbed use significantly declined from 11.0% in 2001 to 1.6% in 2015 (P < 0.001). There were significantly higher rates of sunbed use in women (12.5%/2.0%) vs. men (7.3%/1.3%; P < 0.001), in younger persons and in participants with darker skin (type II and III) vs. fair skin (type I). Individuals with sunburns in childhood were significantly more often sunbed users (5.1% vs. 4.6%; P = 0.002). A remarkable decline of sunbed use was observed after 2009 (7.0% in 2001-2008 and 2.2% in 2009-2015). This reduction occurred in the time of a legal ban of sunbed use for minors but also with the start of the national skin cancer screening programme. CONCLUSION: Use of sunbeds in the German adult population has dropped by more than 85% in the past decade. Primary prevention, including the large public awareness following the legal ban of sunbed use for young people and the effects of the statutory skin cancer screening programme may have contributed to this.

Prevalence of sun-protective behaviour and intentional sun tanning in German adolescents and adults: results of a nationwide telephone survey.

BACKGROUND: The incidence rate of melanoma in the Caucasian population is rising worldwide. One of the major environmental risk factors for melanoma is the exposure to ultraviolet (UV) radiation. To prevent skin damage caused by UV exposure, several organizations recommend wearing protective clothing, staying in the shade, avoiding the outdoors during midday and using sunscreen. OBJECTIVE: To provide representative data on factors associated with sun-protective behaviours and intentional sun exposure during summertime in the German population. METHODS: A population-based sample of 3000 German residents aged 14-45 years (response: 32.1%) was interviewed via telephone from October to December 2015. Survey participants provided data on the use of recommended sun-protective measures on a sunny summer day and their intentional sun exposure during summertime. Data were weighted by age, sex, educational level and federal state to ensure the national representativeness of the sample. RESULTS: Wearing long-sleeved clothes was the most frequently reported protective measure (53.9%), while wearing headgear was the least common (17.9%). Significantly lower frequencies of almost all recommended sun-protective measures were identified for males, participants between 14 and 25 years, those with an immigrant background and those with low levels of education. Using sun protection was positively associated with female gender (OR = 1.62), higher levels of education (ORhigh = 1.27), sunburn during childhood (OR = 1.33) and paying attention to healthy nutrition (OR = 1.64; all P < 0.05). Sun tanning behaviour was associated with female gender (OR = 1.42), younger age, lower level of education, sunbed use (OR = 5.24) and smoking status (OR = 1.50; all P < 0.001). CONCLUSION: As individual sun-protective measures are easy to implement and provide effective protection against high-risk UV exposure, campaigns on skin cancer prevention in Germany should put a stronger focus on young adults, men, less educated individuals and those with immigration background.

First evaluation of the Behavioral Addiction Indoor Tanning Screener (BAITS) in a nationwide representative sample.

BACKGROUND: Evidence suggests that indoor tanning may have addictive properties. However, many instruments for measuring indoor tanning addiction show poor validity and reliability. Recently, a new instrument, the Behavioral Addiction Indoor Tanning Screener (BAITS), has been developed. OBJECTIVES: To test the validity and reliability of the BAITS by using a multimethod approach. METHODS: We used data from the first wave of the National Cancer Aid Monitoring on Sunbed Use, which included a cognitive pretest (August 2015) and a Germany-wide representative survey (October to December 2015). In the cognitive pretest 10 users of tanning beds were interviewed and 3000 individuals aged 14-45 years were included in the representative survey. Potential symptoms of indoor tanning addiction were measured using the BAITS, a brief screening survey with seven items (answer categories: yes vs. no). Criterion validity was assessed by comparing the results of BAITS with usage parameters. Additionally, we tested internal consistency and construct validity. RESULTS: A total of 19·7% of current and 1·8% of former indoor tanning users were screened positive for symptoms of a potential indoor tanning addiction. We found significant associations between usage parameters and the BAITS (criterion validity). Internal consistency (reliability) was good (Kuder-Richardson-20, 0·854). The BAITS was shown to be a homogeneous construct (construct validity). CONCLUSIONS: Compared with other short instruments measuring symptoms of a potential indoor tanning addiction, the BAITS seems to be a valid and reliable tool. With its short length and the binary items the BAITS is easy to use in large surveys.

Interval cancers after skin cancer screening: incidence, tumour characteristics and risk factors for cutaneous melanoma.

BACKGROUND: The rate of interval cancers is an established indicator for the performance of a cancer-screening programme. METHODS: We examined the incidence, tumour characteristics and risk factors of melanoma interval cancers that occurred in participants of the SCREEN project, which was carried out 2003/2004 in Schleswig-Holstein, Germany. Data from 350 306 SCREEN participants, who had been screened negative for melanoma, were linked to data of the state cancer registry. Melanoma interval cancers were defined as melanomas diagnosed within 4-24 months after SCREEN examination. Results were compared with melanomas of the pre-SCREEN era (1999-2002), extracted from the cancer registry. RESULTS: The overall relative incidence of melanoma interval cancers in terms of observed/expected ratio was 0.93 (95% CI: 0.82-1.05; in situ: 1.61 (1.32-1.95), invasive: 0.71 (0.60-0.84)). Compared with melanomas of the pre-SCREEN era, the interval melanomas were thinner and had a slightly greater proportion of lentigo maligna melanomas whereas nodular melanomas were less frequent. INTERPRETATION: The results indicate a moderate performance of the SCREEN intervention with an excess of in situ melanomas. In part, the findings might be due to specifics of the SCREEN project, in particular a short-term follow-up of patients at high risk for melanoma.

Stepwise diagnosis in covert hepatic encephalopathy: critical flicker frequency and MELD-score as a first-step approach.

BACKGROUND: The diagnosis of covert hepatic encephalopathy (CHE) by means of portosystemic encephalopathy syndrome (PSE) test is costly and therefore infrequently performed. AIM: To determine the ability of critical flicker frequency (CFF) alone or in combination with laboratory findings, as an initial test to pre-select which patients should undergo further testing for the diagnosis of covert hepatic encephalopathy. METHODS: This single-centre study included all patients with cirrhosis who underwent PSE and CFF in 2011. CHE was defined by abnormal PSE test. Logistic regression analysis was performed to identify predictors of CHE. ROC curves were used to identify cut-offs of these independent predictors. RESULTS: One hundred and seventeen patients were included. Seventy (60%) had CHE with a higher MELD [16 (IQR 13-21); P = 0.001] and lower CFF [38 Hz (IQR 36-41) P = 0.0011]. On multivariate analyses, CFF [OR 0.83 (95% CI 0.74-0.94)] and MELD [OR 1.13 (95% CI 1.04-1.22)] were identified as independent predictors of CHE. Sensitivity and specificity of a CFF cut-off of 43 Hz was 93.5% and 42.9%, and for a MELD cut-off of 24, it was 97.5% and 32.8% respectively. Most patients with a MELD-Score <24 and a CFF >43 Hz did not have CHE (78%) and with a MELD-Score >24 and CFF <43 Hz most patients had CHE (85%). Therefore, 27% of patients could avoid further testing with a diagnostic accuracy of 81%. CONCLUSION: The combination of MELD-score and critical flicker frequency may be used as a first diagnostic step to filter patients, in whom further covert hepatic encephalopathy testing could be avoided.

[Prevalence, risk groups, and reasons for sunbed use in Germany]. / Prävalenz, Risikogruppen und Motive der Solariennutzung in Deutschland.

BACKGROUND: Ultraviolet (UV) radiation of sunbeds has been classified carcinogenic by the International Agency for Research on Cancer (IARC). Unlike in other countries the available data on the important risk factor has been lacking until recently in Germany. OBJECTIVES: The SUN-Study 2012 (Sunbed-Use: Needs for Action Study) aimed at identifying epidemiological prevalence data concerning this completely preventable risk factor. MATERIALS AND METHODS: A total of 4,851 participants aged 14-45 years were selected from the German population in a representative manner and were surveyed via standardized telephone interviews. The survey period was split into a summer and a winter wave in order to take possible season effects into account. RESULTS: Four out of 10 Germans aged 14-45 years (39.2 %; 95 % CI 37.8-40.6 %) have ever used a sunbed. Within the last year 14.6 % (95 % CI 13.6-15.6 %) visited a sunbed. Current users reported six visits per year on average and every twentieth reported a family history of cutaneous malignant melanoma in first-degree relatives. More than 5 % of minors currently used sunbeds despite the nationwide ban, mostly at unsupervised locations. Half of those minors did not know about the legal ban of sunbed use for minors. CONCLUSIONS: Our study proves that sunbed use which is an important risk factor for skin cancer is widely used. Moreover, considerable information deficits about health risks exist among the German population.

Sunbed use in Germany: trends, user histories and factors associated with cessation and readiness to change.

BACKGROUND: Sunbed use is considered carcinogenic in humans. Studies that examine behavioural patterns related to sunbed use over time are needed for developing skin cancer prevention strategies. OBJECTIVES: To explore age-related trends in the initiation age, to investigate individual histories of sunbed use and to identify characteristics associated with cessation. METHODS: We analysed cross-sectional data of 4851 sunbed users and nonusers from a representative sample of Germans, aged 14-45 years, interviewed in 2011/2012. Biographical data were reconstructed based on reported tanning frequency/duration and changes in sunbed use over time. We used survival analysis to model the initiation age and created birth cohorts to assess age-related trends. Characteristics associated with sunbed use cessation were identified using logistic regression. RESULTS: Among sunbed users, median sunbed exposure was 180 min per year. Annual exposure remained constant in 85·6% of this subgroup with no changes over time during periods of sunbed use. Age at initiation decreased significantly across birth cohorts from 25 to 19 years (25th percentile; cohorts 1966-75 to 1986-93). Characteristics associated with sunbed use cessation included educational level [odds ratios (OR) 1·53 and 1·71 for medium and high education, respectively], greater awareness of skin cancer risk (OR 2·41) and immigrant background (OR 0·54; all P < 0·01). CONCLUSIONS: Initiation of sunbed use at an increasingly younger age suggests the need for interventions targeted at young adults. Approaches that increase general skin cancer risk awareness and that are sensitive to participants' educational level and immigrant background may also be helpful.

UVA-induced DNA double-strand breaks result from the repair of clustered oxidative DNA damages.

UVA (320-400 nm) represents the main spectral component of solar UV radiation, induces pre-mutagenic DNA lesions and is classified as Class I carcinogen. Recently, discussion arose whether UVA induces DNA double-strand breaks (dsbs). Only few reports link the induction of dsbs to UVA exposure and the underlying mechanisms are poorly understood. Using the Comet-assay and γH2AX as markers for dsb formation, we demonstrate the dose-dependent dsb induction by UVA in G(1)-synchronized human keratinocytes (HaCaT) and primary human skin fibroblasts. The number of γH2AX foci increases when a UVA dose is applied in fractions (split dose), with a 2-h recovery period between fractions. The presence of the anti-oxidant Naringin reduces dsb formation significantly. Using an FPG-modified Comet-assay as well as warm and cold repair incubation, we show that dsbs arise partially during repair of bi-stranded, oxidative, clustered DNA lesions. We also demonstrate that on stretched chromatin fibres, 8-oxo-G and abasic sites occur in clusters. This suggests a replication-independent formation of UVA-induced dsbs through clustered single-strand breaks via locally generated reactive oxygen species. Since UVA is the main component of solar UV exposure and is used for artificial UV exposure, our results shine new light on the aetiology of skin cancer.

Effectiveness of skin cancer screening programmes.

Skin cancer, nonmelanoma skin cancer (NMSC) and cutaneous malignant melanoma (CMM), is the most frequent cancer worldwide. It is amenable to early detection, and screening for skin cancer has the potential to reduce mortality and morbidity. However, there are no recommendations for population-based skin cancer screening programmes due to the lack of evidence for the effectiveness from epidemiological studies. In 2008 the first nationwide screening programme for NMSC and CMM in the world was established in Germany. The decision for implementing such a programme was based on the results and evidence of a pilot study that was conducted from 2003 to 2004. The pilot study revealed that a population-based screening programme for skin cancer is feasible and effective. Careful evaluation of the nationwide programme is crucial to generate strong evidence for long-term public health benefits.

Skin cancer screening participation and impact on melanoma incidence in Germany--an observational study on incidence trends in regions with and without population-based screening.

BACKGROUND: The SCREEN (Skin Cancer Research to provide Evidence for Effectiveness of Screening in Northern Germany) project involved population-wide skin cancer screening with whole-body examination by general physicians and dermatologists. It was conducted in the German state of Schleswig-Holstein (July 2003-June 2004), but not in the German state of Saarland. METHODS: The population-based registries of Schleswig-Holstein and Saarland provided data on melanoma incidence before, during, and after SCREEN to assess the association of skin cancer screening with incidence. RESULTS: Approximately 19% of the Schleswig-Holstein population participated in SCREEN (women: 27%, men: 10%). A total of 52% of all melanomas diagnosed during SCREEN in Schleswig-Holstein were detected as part of the project. Melanoma incidence increased during SCREEN (invasive melanoma in women: +8.9 per 100,000 (95% confidence intervals (CI): 6.1; 11.7); men: +4.0 per 100,000 (95% CI: 1.6; 6.4)) and decreased afterwards (women: -10.6 per 100,000 (95% CI: -13.3; -7.9); men: -4.1 per 100,000 (95% CI: -6.5; -1.7)). Similar changes were not observed in Saarland that had no such project. The differences between the two states were greatest among women, the group with the greater SCREEN participation. CONCLUSION: The SCREEN project had a substantial impact on melanoma incidence. This is consistent with the impact of effective screening for other cancers.

[UV risk perception by the general public: results of a representative questionnaire in Germany]. / UV-Risikowahrnehmung in der Bevölkerung: Ergebnisse einer repräsentativen Umfrage in Deutschland.

AIM OF THE STUDY: For public health promotion purposes it is important to know how the general public perceives the risk factor "UV exposure" and how UV risk perception is connected to health-related attitudes and beliefs. The aim of the study was to collect representative data about UV risk perception in Germany. METHODS: A representative telephone survey using the ADM design was carried out among 1 501 German residents between May and July 2007. Variables related to UV risk knowledge, relevance of risk topics in every-day thinking and risk estimates were investigated. Data regarding a subjective benefit evaluation of UV exposition was also collected. RESULTS: The results suggest no essential gaps in the general knowledge about UV risks, except for the underestimation of UV-related cataracts. The respondents thought it extremely likely that UV exposure would cause health damage such as skin cancer, photoaging or sun burns. People were asked to report how often they had thought about a number of health risks including UV risks in the last two weeks. It was established that UV risks are present but not dominant in people's every-day thinking. Along with it, the risk evaluation proves to be rather moderate. The mean value for respondents' perceived personal risk is M=5.1, in the midsection of the given 10-point scale. The results show that perceived personal risk is not influenced by the serious UV health risks such as cancer or cataracts. The results also indicate that UV benefit and UV risk perception are not strongly related to one another. CONCLUSIONS: In summary, participants' perception and assessment of the various health risks of UV exposure seem to be realistic, but the UV risk assessment it is not related to the perception of personal risk. One must therefore assume that UV health risk information and education campaigns do not necessarily lead to a change in the perception of personal UV risk. Rather than addressing primarily risk knowledge, UV risk communication should focus more on motivational aspects and consider the role of UV benefit perception.

UVA radiation causes DNA strand breaks, chromosomal aberrations and tumorigenic transformation in HaCaT skin keratinocytes.

The role of UVA-radiation-the major fraction in sunlight-in human skin carcinogenesis is still elusive. We here report that different UVA exposure regime (4 x 5 J/cm(2) per week or 1 x 20 J/cm(2) per week) caused tumorigenic conversion (tumors in nude mice) of the HaCaT skin keratinocytes. While tumorigenicity was not associated with general telomere shortening, we found new chromosomal changes characteristic for each recultivated tumor. Since this suggested a nontelomere-dependent relationship between UVA irradiation and chromosomal aberrations, we investigated for alternate mechanisms of UVA-dependent genomic instability. Using the alkaline and neutral comet assay as well as gamma-H2AX foci formation on irradiated HaCaT cells (20-60 J/cm(2)), we show a dose-dependent and long lasting induction of DNA single and double (ds) strand breaks. Extending this to normal human skin keratinocytes, we demonstrate a comparable damage response and, additionally, a significant induction and maintenance of micronuclei (MN) with more acentric fragments (indicative of ds breaks) than entire chromosomes particularly 5 days post irradiation. Thus, physiologically relevant UVA doses cause long-lasting DNA strand breaks, a prerequisite for chromosomal aberration that most likely contribute to tumorigenic conversion of the HaCaT cells. Since normal keratinocytes responded similarly, UVA may likewise contribute to the complex karyotype characteristic for human skin carcinomas.

Effectiveness of information campaigns.

Skin cancer represents the most common type of cancer in the white population worldwide and the incidence has dramatically increased during the last decades. UV-radiation is believed to be the most important risk factor responsible for this trend. The prominent role of UV-radiation renders skin cancer most suitable for primary prevention, because the main risk factor can easily be avoided by sticking to simple rules for the behaviour in the sun or under artificial UV (e.g. sunbeds). Since UV-exposure cannot and should not be avoided totally especially due to the beneficial health effects of UV-irradiation like Vitamin D(3)-production, recommendations and information for the public should be as clear and as weighted as possible, through adequate messages, such as: "Love the sun and protect your skin". For that purpose the Association of Dermatological Prevention in Germany (ADP) developed the period of life programme (POLP) that defines certain age-specific target groups, with the aim to give well adapted prevention messages to the population during lifetime. Evaluation of primary prevention campaigns in Germany showed that due to continuous intervention programs during the last 16 years changes in the "sun-behaviour" of the population have been achieved leading to a reduced but sufficient exposure to solar UV-irradiation. This will then contribute to the aim of decreasing morbidity and mortality of skin cancer.

Comparison of risk patterns in carcinoma and melanoma of the skin in men: a multi-centre case-case-control study.

We directly compared risk factors between 214 histologically confirmed melanomas (CMM), 215 basal-cell carcinomas (BCC) and 139 squamous-cell carcinomas (SCC) in a multiple case-case-control study with 349 controls from patients without dermatological disease admitted to the same hospitals. Subjects with fair hair had a significant risk increase for all types of tumours at a comparable level (OR(adj) for blonde hair: CMM 2.3; SCC 2.4; BCC 2.3). The effect of pale eyes was significant and similar for CMM and BCC (OR(adj) 2.6). Intermittent sun exposure measured in hours spent at beach during holidays was significant for both CMM (OR(adj) 2.6 for more than 7000 lifelong hours) and BCC (OR(adj) 2.1 for more than 7000 lifelong hours), while SCC exhibited a significant risk increase for chronic exposure to sunlight measured in hours of outdoor work (OR(adj) 2.2 for more than 6000 lifelong hours). In the case-case comparison using a multinomial logistic regression model, we found a statistically significant risk difference for pale eyes, and number of naevi in the CMM group, compared to other skin cancers. For intermittent sun exposure, there was a significant risk difference of BCC when compared to the risk of SCC. Factors influencing risk of SCC are different, with chronic exposure to sun playing a major role in causing this type of carcinoma.

[Prevention of skin cancer. Necessity, implementation and success]. / Prävention von HautkrebsNotwendigkeit, Durchführung und Erfolg.

Including malignant melanoma, basal cell carcinoma, and squamous cell carcinoma, skin cancer is the cancer with the highest incidence worldwide. Its incidence is increasing more rapidly than that of all other kinds of cancer. It is necessary to slow down this trend through preventive steps in order to reduce morbidity and mortality rates and to decrease the financial burden on the health systems. This goal could be achieved through primary (prevention of risk factors) and secondary prevention (early diagnosis and screening). This essay describes the necessity, realization, and success of these kinds of intervention programs. It especially portrays the procedures in Germany as they have been practiced for the last 15 years by the Society of Dermatology Prevention and German Cancer Aid.