Rüdiger Greinert

International trends in the incidence of malignant melanoma 1953–2008—are recent generations at higher or lower risk?

The incidence of cutaneous malignant melanoma has steadily increased over the past 50 years in predominately fair‐skinned populations. This increase is reported to have leveled off recently in several Northern and Western European countries, Australia, New Zealand and in North America. We studied the global patterns and time trends in incidence of melanoma by country and sex, with a focus on and age‐ and cohort‐specific variations. We analyzed the incidence data from 39 population‐based cancer registries, examining all‐ages and age‐truncated standardized incidence rates of melanoma, estimating the annual percentage change and incidence rate ratios from age‐period‐cohort models. Incidence rates of melanoma continue to rise in most European countries (primarily Southern and Eastern Europe), whereas in Australia, New Zealand, the U.S., Canada, Israel and Norway, rates have become rather stable in recent years. Indications of a stabilization or decreasing trend were observed mainly in the youngest age group (25–44 years). Rates have been rising steadily in generations born up to the end of the 1940s, followed by a stabilization or decline in rates for more recently born cohorts in Australia, New Zealand, the U.S., Canada and Norway. In addition to the birth cohort effect, there was a suggestion of a period‐related influence on melanoma trends in certain populations. Although our findings provide support that primary and secondary prevention can halt and reverse the observed increasing burden of melanoma, they also indicate that those prevention measures require further endorsement in many countries.

Sun exposure and number of nevi in 5- to 6-year-old European children

The occurrence and number of melanocytic nevi are among the most important known risk factors for the development of malignant melanoma. Studying the causes of nevi should lead to successful strategies in the prevention of melanoma. Among 11,478 white German children of preschool age the association between benign melanocytic nevi and a number of risk factors for skin cancer was examined. We found that subjects with a reported history of increased sun exposure, for example, painful sunburns, and an increased number of holidays in foreign countries with a sunny climate had significantly higher nevus counts than individuals without these characteristics. Our results provide further evidence that nevus counts may not only be part of a genetic predisposition but also a result of increased exposure to ultraviolet radiation. Together with the fact that a high nevus count is the most relevant risk factor for malignant melanoma, the results strongly indicate a connection between UV-radiation and the development of melanocytic skin cancer. In conclusion, strategies to reduce the incidence of melanoma should begin with young children.

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 × 5u2009J/cm2 per week or 1 × 20u2009J/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 (20–60u2009J/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.

European Code against Cancer 4th Edition: 12 ways to reduce your cancer risk

This overview describes the principles of the 4th edition of the European Code against Cancer and provides an introduction to the 12 recommendations to reduce cancer risk. Among the 504.6 million inhabitants of the member states of the European Union (EU28), there are annually 2.64 million new cancer cases and 1.28 million deaths from cancer. It is estimated that this cancer burden could be reduced by up to one half if scientific knowledge on causes of cancer could be translated into successful prevention. The Code is a preventive tool aimed to reduce the cancer burden by informing people how to avoid or reduce carcinogenic exposures, adopt behaviours to reduce the cancer risk, or to participate in organised intervention programmes. The Code should also form a base to guide national health policies in cancer prevention. The 12 recommendations are: not smoking or using other tobacco products; avoiding second-hand smoke; being a healthy body weight; encouraging physical activity; having a healthy diet; limiting alcohol consumption, with not drinking alcohol being better for cancer prevention; avoiding too much exposure to ultraviolet radiation; avoiding cancer-causing agents at the workplace; reducing exposure to high levels of radon; encouraging breastfeeding; limiting the use of hormone replacement therapy; participating in organised vaccination programmes against hepatitis B for newborns and human papillomavirus for girls; and participating in organised screening programmes for bowel cancer, breast cancer, and cervical cancer.

European Code against Cancer 4th Edition: Ultraviolet radiation and cancer §

Ultraviolet radiation (UVR) is part of the electromagnetic spectrum emitted naturally from the sun or from artificial sources such as tanning devices. Acute skin reactions induced by UVR exposure are erythema (skin reddening), or sunburn, and the acquisition of a suntan triggered by UVR-induced DNA damage. UVR exposure is the main cause of skin cancer, including cutaneous malignant melanoma, basal-cell carcinoma, and squamous-cell carcinoma. Skin cancer is the most common cancer in fair-skinned populations, and its incidence has increased steeply over recent decades. According to estimates for 2012, about 100,000 new cases of cutaneous melanoma and about 22,000 deaths from it occurred in Europe. The main mechanisms by which UVR causes cancer are well understood. Exposure during childhood appears to be particularly harmful. Exposure to UVR is a risk factor modifiable by individuals behaviour. Excessive exposure from natural sources can be avoided by seeking shade when the sun is strongest, by wearing appropriate clothing, and by appropriately applying sunscreens if direct sunlight is unavoidable. Exposure from artificial sources can be completely avoided by not using sunbeds. Beneficial effects of sun or UVR exposure, such as for vitamin D production, can be fully achieved while still avoiding too much sun exposure and the use of sunbeds. Taking all the scientific evidence together, the recommendation of the 4th edition of the European Code Against Cancer for ultraviolet radiation is: Avoid too much sun, especially for children. Use sun protection. Do not use sunbeds.

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.

The role of vitamin D in cancer prevention: does UV protection conflict with the need to raise low levels of vitamin D?

BACKGROUNDnVitamin D is essential for life. Part of the bodys supply of vitamin D is ingested in food, but UV induced vitamin D synthesis in the body plays an even more important role. UV irradiation is a cause for the currently rising incidence of skin cancer in many countries; on the other hand, Vitamin D might be protective against some cancers. In this paper we summarize the current data on vitamin D and cancer and on the vitamin D status of populations in Europe and discuss whether current recommendations on UV protection require changes.nnnMETHODSnIn 2008, the International Agency for Research on Cancer (IARC) published a systematic review on vitamin D and cancer. We describe its main findings and review additional publications retrieved by a selective literature search on vitamin D, UV light, and skin cancer. In addition, we systematically review the current recommendations on vitamin D supplementation.nnnRESULTSnHigher vitamin D levels are associated with a lower risk of colon cancer. For breast cancer, the situation is less clear. In general, higher vitamin D levels are associated with lower overall mortality. Concerning optimal Vitamin D levels, serum values ≥ 50 nmol/L (ie.. ≥ 20 ng/mL) are frequently discussed, and a few authors favor markedly higher values. Brief UV exposures are usually adequate for endogenous vitamin D synthesis.nnnCONCLUSIONnMore research is needed into the possible protective effects of vitamin D against cancer. Brief, daily UV exposure stimulates vitamin D production and causes negligible skin damage. Raising the vitamin D level even further by extended solar UV exposure or irradiation in a solarium is inadvisable because of the risk of skin cancer. Oral vitamin D supplementation can be considered as an alternative, particularly for persons at high risk, such as the elderly and members of certain ethnic groups.

Influence of GSM signals on human peripheral lymphocytes: study of genotoxicity.

Exposure to radiofrequency (RF) electromagnetic fields (EMF) is continuously increasing worldwide. Yet, conflicting results of a possible genotoxic effect of RF EMF continue to be discussed. In the present study, a possible genotoxic effect of RF EMF (GSM, 1,800 MHz) in human lymphocytes was investigated by a collaboration of six independent institutes (institutes a, b, c, d, e, h). Peripheral blood of 20 healthy, nonsmoking volunteers of two age groups (10 volunteers 16–20 years old and 10 volunteers 50–65 years old) was taken, stimulated and intermittently exposed to three specific absorption rates (SARs) of RF EMF (0.2 W/kg, 2 W/kg, 10 W/kg) and sham for 28 h (institute a). The exposures were performed in a setup with strictly controlled conditions of temperature and dose, and randomly and automatically determined waveguide SARs, which were designed and periodically maintained by ITIS (institute h). Four genotoxicity tests with different end points were conducted (institute a): chromosome aberration test (five types of structural aberrations), micronucleus test, sister chromatid exchange test and the alkaline comet assay (Olive tail moment and % DNA). To demonstrate the validity of the study, positive controls were implemented. The genotoxicity end points were evaluated independently by three laboratories blind to SAR information (institute c = laboratory 1; institute d = laboratory 2; institute e = laboratory 3). Statistical analysis was carried out by institute b. Methods of primary statistical analysis and rules to adjust for multiple testing were specified in a statistical analysis plan based on a data review before unblinding. A linear trend test based on a linear mixed model was used for outcomes of comet assay and exact permutation test for linear trend for all other outcomes. It was ascertained that only outcomes with a significant SAR trend found by at least two of three analyzing laboratories indicated a substantiated suspicion of an exposure effect. On the basis of these specifications, none of the nine end points tested for SAR trend showed a significant and reproducible exposure effect. Highly significant differences between sham exposures and positive controls were detected by each analyzing laboratory, thus validating the study. In conclusion, the results show no evidence of a genotoxic effect induced by RF EMF (GSM, 1,800 MHz).

European Code against Cancer 4th Edition: Ionising and non-ionising radiation and cancer.

Ionising radiation can transfer sufficient energy to ionise molecules, and this can lead to chemical changes, including DNA damage in cells. Key evidence for the carcinogenicity of ionising radiation comes from: follow-up studies of the survivors of the atomic bombings in Japan; other epidemiological studies of groups that have been exposed to radiation from medical, occupational or environmental sources; experimental animal studies; and studies of cellular responses to radiation. Considering exposure to environmental ionising radiation, inhalation of naturally occurring radon is the major source of radiation in the population - in doses orders of magnitude higher than those from nuclear power production or nuclear fallout. Indoor exposure to radon and its decay products is an important cause of lung cancer; radon may cause approximately one in ten lung cancers in Europe. Exposures to radon in buildings can be reduced via a three-step process of identifying those with potentially elevated radon levels, measuring radon levels, and reducing exposure by installation of remediation systems. In the 4th Edition of the European Code against Cancer it is therefore recommended to: Find out if you are exposed to radiation from naturally high radon levels in your home. Take action to reduce high radon levels. Non-ionising types of radiation (those with insufficient energy to ionise molecules) - including extremely low-frequency electric and magnetic fields as well as radiofrequency electromagnetic fields - are not an established cause of cancer and are therefore not addressed in the recommendations to reduce cancer risk.

The German SCREEN project – design and evaluation of the communication strategy

BACKGROUNDnSkin cancer is the most common cancer in light-skinned populations worldwide. Primary and secondary preventive activities such as skin cancer screening are intended to reduce skin cancer burden. In 2003, a population-based skin cancer screening project [SCREEN (Skin Cancer Research to Provide Evidence for Effectiveness of Screening in Northern Germany)] was conducted in Northern Germany with more than 360,000 people screened. SCREEN was supported by a communication intervention that was aimed at informing the population about skin cancer, its risk factors and the screening intervention as well as preparing the health professionals for the project. Within SCREEN both physicians and practice nurses were educated in counselling. The aim of the present article is to describe and evaluate the communication strategy accompanying SCREEN.nnnMETHODSnTwo computer-assisted telephone interview surveys were performed in April/May 2003 and May 2004. Participants had to be members of the statutory health insurance and be aged 20 years. They were asked about knowledge of skin cancer, perception of physicians performance and skin cancer screening in general. Data are mainly presented in a descriptive manner. For statistical analyses, Mann-Whitney U test and Pearsons chi-square test were used.nnnRESULTSnKnowledge about sunburn in childhood and high ultraviolet exposure as skin cancer risk factors increased during SCREEN. Simultaneously, the awareness for early detection of skin cancer increased significantly from 41.3 to 74.0% (P < 0.001). A total of 21.5% of the interviewees participated in the skin cancer screening project, similar to the population-based participation rate reached.nnnCONCLUSIONnA comprehensive communication strategy accompanying a screening intervention improves the knowledge of potential screenees and may additionally increase the participation rate.