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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.

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 G1-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.

a population-based skin cancer screening project was conducted in SchleswigHolstein, 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. METHODS: Trends in melanoma mortality rates for Schleswig-Holstein and the adjacent regions (Denmark and the German federal states of Mecklenburg-Vorpommern, Hamburg, and Lower Saxony) and in Germany excluding Schleswig-Holstein were compared. Log-linear regression was used to assess mortality trends. RESULTS: In Schleswig-Holstein during the pre skin cancer screening period (1998)(1999), the age-standardized melanoma mortality rate (World standard population) was 1.9 per 100,000 for men and 1.4 per 100,000 for women. Melanoma mortality declined by 47% to 1.0 per 100,000 men and by 49% to 0.7 per 100,000 women by 2008/2009. The annual percentage change in the most recent 10-year period (2000-2009) was À7.5% (95% confidence interval, À14.0, À0.5) for men and À7.1% (95% confidence interval, À10.5, À2.9) for women. In each of the 4 adjacent regions and in the rest of Germany, mortality rates were stable, and the decline in Schleswig-Holstein was significantly different from the changes observed in all of the other areas studied. CONCLUSIONS: The current data represent strong evidence, but not absolute proof, that the skin cancer screening program produced a reduction in melanoma mortality in Schleswig-Holstein.

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.

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 Â 5 J/cm 2 per week or 1 Â 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 c-H2AX foci formation on irradiated HaCaT cells (20-60 J/cm 2 ), we show a dosedependent 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.

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 populationbased 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.

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