Beate Volkmer

Does skin cancer screening save lives?: an observational study comparing trends in melanoma mortality in regions with and without screening.

From July 1, 2003 to June 30, 2004, a population‐based skin cancer screening project was conducted in Schleswig‐Holstein, Germany. In total, 360,288 individuals aged ≥20 years were screened by means of a whole‐body examination. In this report, the authors compare trends in melanoma mortality in Schleswig‐Holstein with those in all adjacent regions, none of which had population‐based skin cancer screening.

Non-Melanoma Skin Cancer Incidence and Impact of Skin Cancer Screening on Incidence

Non-melanoma skin cancer (NMSC) is the most common malignancy, whose public health significance is often unrecognized. This analysis has two objectives: first, to provide up-to-date incidence estimates by sex, age group, histological type, and body site; and second, to study the impact of skin cancer screening. The impact of screening on NMSC incidence in Schleswig-Holstein, Germany, is analyzed by comparing four time periods of different screening settings (no screening (1998-2000), pilot project (Skin Cancer Research to Provide Evidence for Effectiveness of Screening in Northern Germany, SCREEN, 2003-2004), after SCREEN (2004-2008), and nation-wide skin cancer screening (2008-2010)) to a reference region (Saarland, Germany). Age-standardized (Europe) NMSC incidence was 119/100,000 for women and 145/100,000 for men in the most recent screening period in Schleswig-Holstein (2008-2010). During implementation of SCREEN (2003-2004), incidence increased from 81.5/100,000 to 111.5/100,000 (1998-2000) by 47% for women and 34% for men. All age groups in women were affected by the increase, but increases for men were mostly limited to the older age groups. Incidence in Saarland first increased slowly, but increased steeply with the introduction of the nation-wide skin cancer screening in 2008 (+47% for women and +40% for men, reference 2004-2008). Observed changes are most likely attributed to screening activities.

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.

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 × 5 J/cm2 per week or 1 × 20 J/cm2 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 γ-H2AX foci formation on irradiated HaCaT cells (20–60 J/cm2), 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.

Sunbed Use, User Characteristics, and Motivations for Tanning Results From the German Population-Based SUN-Study 2012

OBJECTIVES To calculate sunbed use prevalence rates, to investigate the motivations for tanning, and to identify typical target groups for interventions to prevent skin cancer. DESIGN Cross-sectional, representative, population-based study, primary analysis of the SUN-Study 2012 (Sunbed-Use: Needs for Action-Study). SETTING Nationwide telephone survey of the general population in Germany. PARTICIPANTS Study participants (n=4851) aged 14 to 45 years. MAIN OUTCOME MEASURES Frequency of sunbed use and, if applicable, motivational reasons for use, the location of the most recent use, and the available advisory service. Characteristics of typical sunbed users were identified using logistic regression analysis. RESULTS The overall prevalence of sunbed use was 39.2% (ever users); 14.6% had used a sunbed within the last 12 months (current users). Among minors and persons with skin types I or II, this proportion was 5.2% and 8.9%, respectively. Positive determinants of current sunbed use (quantified as odds ratios [95% CIs]) were female sex (1.97 [1.64-2.37]), immigrant background (1.46 [1.21-1.77]), and full-time (1.93 [1.53-2.43]) or part-time employment (1.44 [1.11-1.85]). The main motivations for tanning were relaxation and increased attractiveness. Sunbeds were mainly used in tanning studios (74.9%), and many users had never been advised about potential health risks (72.8%). CONCLUSIONS The results of this study emphasize the need for more frequent and higher-quality educational interventions to change tanning behavior, particularly among women, people with darker skin, and those with an immigrant background. Owing to their elevated vulnerability, minors and people with pale skin should also be the focus of such interventions.

Frequency of Excisions and Yields of Malignant Skin Tumors in a Population-Based Screening Intervention of 360 288 Whole-Body Examinations

OBJECTIVE To explore the frequency of excisions and yields of histopathologically confirmed skin cancer. DESIGN A population-based skin cancer screening intervention (the SCREEN project) in the German state of Schleswig-Holstein (July 1, 2003, to June 30, 2004). SETTING Physician offices. Participants could choose between nondermatologist physicians and dermatologists for their initial whole-body skin examination. All screening physicians received a mandatory 8-hour training course. PARTICIPANTS Inhabitants of Schleswig-Holstein 20 years or older with statutory health insurance (N = 360,288). MAIN OUTCOME MEASURES Frequency of excisions and yields of malignant skin tumors (malignant melanomas [MMs], basal cell carcinomas [BCCs], and squamous cell carcinomas [SCCs]), stratified by sex and age. RESULTS Overall, 15,983 excisions were performed (1 of 23 screenees). A total of 3103 malignant skin tumors were diagnosed in 2911 persons: 585 MMs, 1961 BCCs, 392 SCCs, and 165 other malignant skin tumors. Overall, 116 persons (3103 of 360,288) had to be screened to find 1 malignant tumor, with 1 of 620 for MM, 1 of 184 for BCC, and 1 of 920 for SCC. Twenty excisions were performed to find 1 melanoma in men 65 years and older, but more than 50 excisions were required to find 1 melanoma in men aged between 20 and 49 years. CONCLUSIONS The results of SCREEN suggest a high yield of malignant skin tumors in a large-scale population-based screening project. We found that a high number of excisions was performed in the youngest screenees with an associated low yield, suggesting a need in screener training to emphasize a more conservative attitude toward excisions in young screenees.

The Dose Dependence of Cyclobutane Dimer Induction and Repair in UVB-irradiated Human Keratinocytes¶

Abstract UVB and UVA components of the solar spectrum or from artificial UV-sources might be important etiological factors for the induction and development of skin cancer. In particular, deficiencies in the capacity to repair UV-induced DNA-lesions have been linked to this phenomenon. However, until now only limited data are available on the biological and physical parameters governing repair capacity. We have, therefore, developed a flowcytometric assay using fluorescence-labeled monoclonal antibodies to study the dose-dependence of induction and repair of UVB-induced cyclobutane pyrimidine dimers in a spontaneously immortalized keratinocytic cell line (HaCaT). Our results show that the kinetics of recognition and incision of UVB-induced DNA lesions slows down by a factor of about 3 in a dose range of 100–800 J m−2. Furthermore, a thorough analysis of repair kinetics indicates that this reduction in repair capacity might not be dependent on saturation of enzymatic repair capacity (Michalis–Menten) but may be caused by a UV-induced impairment of enzymes involved in DNA repair. Because this effect is evident in vitro at doses comparable to the minimal erythemal dose in vivo, our results might have significant impact on risk assessment for UV-induced carcinogenesis.

A nationwide population-based skin cancer screening in Germany: Proceedings of the first meeting of the International Task Force on Skin Cancer Screening and Prevention (September 24 and 25, 2009)

Skin cancer incidence is increasing worldwide in white populations and mortality rates have not declined throughout most of the world. An extraordinarily high proportion of at-risk individuals have yet to be screened for melanoma but guidelines from esteemed bodies do not currently endorse population-based screening. Evidence for the effectiveness of skin cancer screening is imperative. To this end, scientists in Germany have launched a nationwide skin cancer screening campaign. Herein, we review pilot screening data from Schleswig-Holstein, discuss the launch of the major new national initiative, review issues related to evaluation of that program, and propose seven recommendations from the International Task Force on Skin Cancer Screening and Prevention that was held in Hamburg, Germany, on September 24 and 25, 2009.

Assessing the risk of skin damage due to femtosecond laser irradiation.

We irradiated freshly excised skin biopsies with four irradiation regimes usually taken for multiphoton imaging. If there is any skin damaging, it is mainly an effect similar to the damaging effects of UV-irradiation. Using fluorescent antibodies against cyclobutane-pyrimidin-dimers (CPDs) in combination with immuno-fluorescence image analysis we quantitatively compared fs-irradiation effects with UV-irradiation (solar simulator). Based on these results we are giving a risk assessment. The results show that multi photon imaging using the parameters described here is in the ballpark of damaging occurring from every day sun exposure.

UVA and UVB Irradiation Differentially Regulate microRNA Expression in Human Primary Keratinocytes

MicroRNA (miRNA)-mediated regulation of the cellular transcriptome is an important epigenetic mechanism for fine-tuning regulatory pathways. These include processes related to skin cancer development, progression and metastasis. However, little is known about the role of microRNA as an intermediary in the carcinogenic processes following exposure to UV-radiation. We now show that UV irradiation of human primary keratinocytes modulates the expression of several cellular miRNAs. A common set of miRNAs was influenced by exposure to both UVA and UVB. However, each wavelength band also activated a distinct subset of miRNAs. Common sets of UVA- and UVB-regulated miRNAs harbor the regulatory elements GLYCA-nTRE, GATA-1-undefined-site-13 or Hox-2.3-undefined-site-2 in their promoters. In silico analysis indicates that the differentially expressed miRNAs responding to UV have potential functions in the cellular pathways of cell growth and proliferation. Interestingly, the expression of miR-23b, which is a differentiation marker of human keratinocytes, is remarkably up-regulated after UVA irradiation. Studying the interaction between miR-23b and its putative skin-relevant targets using a Luciferase reporter assay revealed that RRAS2 (related RAS viral oncogene homolog 2), which is strongly expressed in highly aggressive malignant skin cancer, to be a direct target of miR-23b. This study demonstrates for the first time a differential miRNA response to UVA and UVB in human primary keratinocytes. This suggests that selective regulation of signaling pathways occurs in response to different UV energies. This may shed new light on miRNA-regulated carcinogenic processes involved in UV-induced skin carcinogenesis.