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Solar UV radiation causes beneficial and detrimental changes in human health. International and national Health agencies recommend avoiding sun exposure when the solar rays are strongest (typically 2 h before and after solar noon). In this study we detail and refine such recommendations. We estimated biologically-effective radiation (inductive of erythema and pre-vitamin D) using spectral solar UV radiation measurements on a horizontal plane at three French sites equipped with spectroradiometers: Villeneuve d'Ascq (VDA) (North of France); Observatoire de Haute-Provence (OHP) (French Southern Alps); and Saint-Denis de La Réunion (SDR) on Réunion Island, in the Indian Ocean. These sites are very different: VDA is a semi-urban site in a flat region, OHP a rural mountainous site and SDR a coastal urban site on a small mountainous island. Biologically active radiation was analyzed by studying erythema induction and measuring pre-vitamin D synthesis. Dose-rates, doses and times for sunburn induction and vitamin D production were derived. Regarding the level of vitamin D dose considered here (1000 IU), we found that at mainland sites time required for vitamin D synthesis was relatively long, even around solar noon, in winter months this could be 2-3 h for phototype II individuals exposing their face and hands. In the tropics vitamin D could always be synthesized in a reasonable time (e.g. 20 min in winter). By contrast, in summer, the required duration times (exposing face, hands, arms and legs) are very short, approximately 2-4 min on the mainland and 1 min in the tropics for phototype II individuals. In all skin phototypes the duration of sun exposure required to induce erythema was generally longer than that to produce vitamin D. These quantitative results, obtained using an instrument measuring on a horizontal plane and with an unobstructed view, do not represent realistic values for human exposure. To account for realistic human body exposure, received doses and times of exposure were adjusted. Our study shows that, mostly in summer, the time periods where limited solar exposure is recommended should be extended, especially at low latitude locations., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

In response to the demand from a growing number of people concerned about the possible impact of RF-EMF on health, the French National Frequency Agency (ANFR) has published a standardized protocol for in-situ measurements of radiofrequency electromagnetic fields (RF-EMF). This protocol was based on the search for the point of highest field strength and the use of spot measurement. In the framework of an epidemiological study, such spot measurements were implemented in the homes of 354 participants located in urban areas within 250 m of a mobile-phone base station (MPBS) and in the main beam direction of the antenna. Among the participants, more than half accepted to be enrolled in a longer-term study, among whom 152 were equipped with a personal exposure meter (PEM) for 48 h and 40 for seven continuous days. Both spot and PEM measurements quantified downlink field strengths, i.e. FM, TV3-4-5, TETRA I-II-III, 2 GHz-5GHz Wi-Fi, WiMax, GSM900, GSM1800, UMTS900, UMTS 2100, LTE800, LTE1800, and LTE2600. Spot measurements showed a mean/median field strength of 0.58/0.44 V/m for total RF-EMF and 0.43/0.27 V/m from the MPBS. RF-EMF from the MPBS was the dominant source of exposure in 64% of households. Exposure to RF-EMF was influenced by the position of the windows with respect to the MPBS, in particular line-of-site visibility, the distance of the antenna and the floor of the apartment. The PEM surveys showed the measured exposure to be higher during outings than at home and during the day than at night, but there was no difference between the weekends and working days. There was a strong correlation between exposure quantified by both spot and PEM measurements, although spot measures were approximately three times higher than those by PEMs. This study is the first to assess exposure to RF-EMF of people living near a MPBS in urban areas in France. These preliminary results suggest the value of using spot measurements to estimate the impact of the evolution of the mobile-phone network and technology on the exposure of populations to RF-EMF. The low levels of RF-RMF expressed as mean values do not necessarily rule out possible health effects of this exposure., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

The effects of radiofrequency exposure on the health of people living near mobile-phone base stations (MPBSs) have been the subject of several studies since the mid-2000s, with contradictory results. We aimed to investigate the association between measured exposure to radiofrequency electromagnetic fields (RF-EMF) from MPBSs and the presence of self-reported non-specific and insomnia-like symptoms. A cross-sectional survey conducted between 2015 and 2017 in five large cities in France involved 354 people living in buildings located at a distance of 250 m or less from an MPBS and in the main transmit beam of the antennas. Information on environmental concerns, anxiety, and non-specific and insomnia-like symptoms was collected with a questionnaire administrated by telephone. A complete broadband field-meter measurement [100 kHz - 6 GHz] was then made at five points of each dwelling, followed by a spectral analysis at the point of highest exposure, detailing the contribution of each service, including MPBS. The median exposure from MPBS was 0.27 V/m (0.44 V/m for global field), ranging from 0.03 V/m to 3.58 V/m, MPBSs being the main source of exposure for 64% of the dwellings. In this study population, the measured exposure from MPBSs was not associated with self-reported non-specific or insomnia-like symptoms. However, for insomnia-like symptoms, a significant interaction was found between RF-EMF exposure from MPBSs and environmental concerns. These findings do not support the hypothesis of an effect of RF-EMF from MPBSs on non-specific or insomnia-like symptoms in the overall population. Studies are needed to further investigate the positive association observed between exposure from MPBSs and insomnia-like symptoms among people reporting environmental concerns., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

In this article, we summarize the research that eventually led to the classification of the full ultraviolet (UV) radiation spectrum as carcinogenic to humans. We recall the pioneering works that led to the formulation of novel hypotheses on the reasons underlying the increasing burden of melanoma in light-skinned populations. It took long before having compelling evidence on the association between UV and melanoma, in particular, the importance of UV exposure during childhood for both the occurrence of melanoma and death. The role of UVA was established only after 2005. If molecular lesions caused by UV radiation are better known, the precise mechanism by which UV exposure drives melanoma occurrence and progression still needs to be elucidated. More research on the UV-melanoma relationships has led to more evidence-based sun-protection recommendations, especially for children, and to effective control of the artificial UV tanning fashion. Since around 1985-1995, the mortality because of melanoma has started to decrease in younger age groups in most light-skinned populations. If sun protection among children remain on top of public health agendas, there is a fairly great chance that melanoma mortality will stabilize and steadily decrease in all light-skinned populations. The introduction of effective therapies against metastatic disease will improve this reversal in mortality trends.

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., (© 2019 European Academy of Dermatology and Venereology.)

Background: In a previous nationwide ecological study based on 20 years of registration and 7,443 cases of acute lymphoblastic leukemia (ALL), we reported a positive association between residential solar ultraviolet (UV) light at diagnosis and childhood precursor B-cell acute lymphoblastic leukemia (PBC-ALL)., Objective: The present study investigated the influence of suspected individual risk factors for ALL on the association between UV and PBC-ALL, and evaluated this association at the residence at birth., Methods: Individual data collected by interviews in the ESCALE (2003-2004) and ESTELLE (2010-2011) nationwide case-control studies, which included 1,511 cases of leukemia aged less than 15 years and 3,102 population controls, were analyzed. Municipalities of residences at birth and at diagnosis/interview were extracted and assigned UV radiation exposure from the EUROSUN database. The potential confounders or effect modifiers considered were strongly suspected risk factors for ALL that were available in the ESCALE and ESTELLE studies., Results: UV exposure at diagnosis was associated with PBC-ALL (OR = 1.27 [1.08-1.48]) for UV > 105.5 J/cm 2 compared to UV ≤ 105.5 J/cm 2 . Considering exposure to UV at birth rather than at diagnosis/inclusion yielded almost identical results as both variables were strongly correlated. Taking into account the suspected ALL risk factors did not affect this association in the pooled study., Conclusion: Our findings suggest that our previous observation of an ecological association between residential UV radiation exposure at diagnosis and PBC-ALL was not confounded or modified by individual risk factors, and that the critical exposure time window may be prenatal.

In this issue of the Journal, Ghiasvand et al. (Am J Epidemiol. 2017;185(3):147-156) present results from a longitudinal study of the association between indoor tanning and melanoma in a large cohort of Norwegian women. These new data further support previous findings on the damaging effects of tanning bed exposure on women, particularly young women. The authors present compelling evidence that early exposure to tanning beds advances the date of diagnosis of melanoma by at least 2 years. With a strong design and a large cohort followed for a mean of 13.7 years, this study lends additional support to previous evidence of the negative effects of tanning beds and provides further justification for stronger policy initiatives designed to reduce tanning bed use among young women., (© The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Appearing in the early 1980s, at a time when UVA was considered as relatively safe, the tanning industry has substantially developed in occidental countries, especially in Northern European countries. In Europe, the erythemally-weighted irradiance of a modern sunbed should not exceed 0.3 W/m 2 , equivalent to an UV index of 12, i.e. to a tropical midday sun, but increased in recent years, the UV spectrum emitted by sunbeds had evolved towards higher UVA irradiance and solariums UV had become even less similar to natural sun.

Purpose: Few studies have investigated the relationship between solar ultraviolet radiation (UV) and childhood hematological malignancies (CHM). This study addresses the associations between residential UV exposure at diagnosis and the incidence of types and subtypes of CHM, by age and gender, in France, over a long period, on the fine scale of the 36,326 Communes that constitute mainland France., Methods: The 9,082 cases of acute leukemia and 3,563 cases of lymphoma diagnosed before the age of 15 years from 1990 to 2009 were provided by the French National Registry of Childhood Hematological Malignancies. The incidence of CHM was calculated by Commune, year, age and gender and expressed as the standardized incidence ratio (SIR). UV data from 1988 to 2007 were extracted from the EUROSUN database., Results: The annual daily average UV exposure of the children ranged from 85.5 to 137.8 J/cm(2). For each additional 25 J/cm(2), there was a significant increase in precursor B-cell acute lymphoblastic leukemia (PBC-ALL) in children aged less than 5 years (SIR 1.18; 95% CI 1.10-1.27). Further analysis of PBC-ALL in the young children suggested a better fit of models with a threshold, with the risk increasing above 100 J/cm(2), for which the SIR was 1.24 (95% CI 1.14-1.36) for a 25 J/cm(2) increase. The results remained stable in analyses stratifying by deprivation index or degree of urbanization of the Communes., Conclusion: The study suggests that higher residential UV exposure may be positively associated with a higher incidence of PBC-ALL in early childhood.

Objectives: Occupational ultraviolet (UV) exposure was evaluated in a population-based sample in France., Methods: A random survey was conducted in 2012 in individuals aged 25 to 69 years. The median daily standard erythemal UV dose (SED) was estimated from exposure time and place and matched to satellite UV records., Results: A total of 889 individuals were exposed to solar UV with highest doses observed among gardeners (1.19 SED), construction workers (1.13 SED), agricultural workers (0.95 SED), and culture/art/social science workers (0.92 SED). Information and communication technology, industry, and transport workers were highly exposed (>0.70 SED). Significant factors associated with high occupational UV exposure were sex (P < 0.0001), phototype (P = 0.0003), and taking lunch outdoors (P < 0.0001)., Conclusions: This study identified not only expected occupations with high UV exposure but also unexpected occupations with high exposures. This could serve as a basis for future prevention.

Excessive exposure to solar ultraviolet (UV) is the main cause of skin cancer. Specific prevention should be further developed to target overexposed or highly vulnerable populations. A better characterisation of anatomical UV exposure patterns is however needed for specific prevention. To develop a regression model for predicting the UV exposure ratio (ER, ratio between the anatomical dose and the corresponding ground level dose) for each body site without requiring individual measurements. A 3D numeric model (SimUVEx) was used to compute ER for various body sites and postures. A multiple fractional polynomial regression analysis was performed to identify predictors of ER. The regression model used simulation data and its performance was tested on an independent data set. Two input variables were sufficient to explain ER: the cosine of the maximal daily solar zenith angle and the fraction of the sky visible from the body site. The regression model was in good agreement with the simulated data ER (R(2)=0.988). Relative errors up to +20% and -10% were found in daily doses predictions, whereas an average relative error of only 2.4% (-0.03% to 5.4%) was found in yearly dose predictions. The regression model predicts accurately ER and UV doses on the basis of readily available data such as global UV erythemal irradiance measured at ground surface stations or inferred from satellite information. It renders the development of exposure data on a wide temporal and geographical scale possible and opens broad perspectives for epidemiological studies and skin cancer prevention.

Purpose: While exposure to ultraviolet radiation (UVR) is a recognized risk factor for cataract, its association is more controversial with age-related macular degeneration (AMD). We report the associations of lifetime exposure to ambient UVR with cataract extraction and AMD., Methods: The Alienor Study is a population-based study of 963 residents of Bordeaux (France), aged 73 years or more. Lifetime exposure to ambient UVR was estimated from residential history and Eurosun satellite-based estimations of ground UVR. It was divided in three groups (lower quartile, intermediate quartiles, upper quartile), using the intermediate quartiles as the reference. Early and late AMD was classified from retinal color photographs. Cataract extraction was defined as absence of the natural lens at slit-lamp., Results: After multivariate adjustment, subjects in the upper quartile of lifetime ambient UVR exposure were at increased risk for cataract extraction (odds ratio [OR] = 1.53; 95% confidence interval [CI], 1.04-2.26; P = 0.03) and for early AMD (OR = 1.59; 95% CI, 1.04-2.44; P = 0.03), by comparison with subjects in the intermediate quartiles. Subjects in the lower quartile of UVR exposure also were at increased risk for early AMD (OR = 1.69; 95% CI, 1.06-2.69; P = 0.03), by comparison with those with medium exposure. Associations of late AMD with UVR exposure was not statistically significant., Conclusions: This study further confirms the increased risk for cataract extraction in subjects exposed to high ambient UVR. Moreover, it suggests that risk for early AMD is increased in subjects exposed to high UVR, but also to low UVR, by comparison with medium exposures., (Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.)

Indoor tanning has substantially grown in USA and Europe, more especially in the sun-deprived Northern countries, but also in more sunny countries such as Queensland, Australia. Several studies have specifically addressed the prevalence of sunbed use by children and adolescents in Northern Europe and in the USA, and showed that up to 40-50% of teenagers 15-18 years old had ever used indoor tanning, the highest figures being observed among girls in Scandinavia and Minnesota. Indoor tanning among adults is mostly prevalent in age classes younger than 45. Epidemiological studies have shown that exposure to sunbeds increases the risk of both melanoma and non-melanoma skin cancers: a meta-analysis of 19 studies published before 2006 showed that ever-use of sunbeds was positively associated with melanoma (summary relative risk, 1.15; 95% CI, 1.00-1.31), and first exposure before 35 years of age significantly increased melanoma risk (7 studies, RR = 1.75; 95% CI, 1.35-2.26). Further epidemiological data documented the links between artificial UV tanning and melanoma: two large case-control studies in Minnesota and Australia yielded higher melanoma risks for ever use of sunbeds: 1.74 (95%CI, 1.42-2.14) and 1.41 (95%CI, 1.01-1.96) respectively, risk increasing with greater use and earlier age at first use. The most compelling evidence derives from a large cohort of Norwegian and Swedish women which showed that melanoma risk increased with accumulating exposure (RR for solarium use ≥1 time per month in two or three decades, 10-39 years, 2.37 (95%CI, 1.37-4.08)). In addition, the analysis of a melanoma epidemic observed in Iceland between 1995 and 2002, on the trunk of women younger than 50, pointed out the possible role of the explosion of exposure to sunbeds in this country after 1985. Exposure to artificial ultraviolet is a risk factor for melanoma. Risk appears modest in the general population, but concentrates in the population that started sunbed use before the age of 35; the risk attributable to sunbed use in melanoma patients younger than 30 may be as high as 43 to 76%. Of particular concern is the use of sunbeds by adolescents. Use of sunbeds should be strongly discouraged, and banned under the age of 18., (This journal is © The Royal Society of Chemistry and Owner Societies 2012)

Background: Breast cancer mortality is declining in many Western countries. If mammography screening contributed to decreases in mortality, then decreases in advanced breast cancer incidence should also be noticeable., Patients and Methods: We assessed incidence trends of advanced breast cancer in areas where mammography screening is practiced for at least 7 years with 60% minimum participation and where population-based registration of advanced breast cancer existed. Through a systematic Medline search, we identified relevant published data for Australia, Italy, Norway, Switzerland, The Netherlands, U.K. and the U.S.A. Data from cancer registries in Northern Ireland, Scotland, the U.S.A. (Surveillance, Epidemiology and End Results (SEER), and Connecticut), and Tasmania (Australia) were available for the study. Criterion for advanced cancer was the tumour size, and if not available, spread to regional/distant sites., Results: Age-adjusted annual percent changes (APCs) were stable or increasing in ten areas (APCs of -0.5% to 1.7%). In four areas (Firenze, the Netherlands, SEER and Connecticut) there were transient downward trends followed by increases back to pre-screening rates., Conclusions: In areas with widespread sustained mammographic screening, trends in advanced breast cancer incidence do not support a substantial role for screening in the decrease in mortality.

In light-skinned populations, the incidence of cutaneous melanoma is highest in summer and lowest in winter. We analyzed the seasonal variation of melanoma incidence in Northern Ireland from 1984 to 2006 according to the Breslow thickness and body site. We also reviewed earlier studies on seasonal variation in the diagnosis of melanoma. Two-thirds of melanomas in women (2028 cases) and one-third of melanomas in men (1230 cases) were diagnosed on the limbs. In both sexes, pronounced seasonal variations were observed in the incidence of invasive melanomas less than 2 mm arising on the limbs. These seasonal variations were mainly noticeable in women of all ages, to a lesser degree in men aged below 50 years, and not in men aged above 50 years. No seasonal variation was observed for melanomas less than 2 mm arising on the trunk or the head and neck nor for melanomas 2 mm thickness or more, irrespective of the age, sex, and body site. Seasonal variations of thin melanomas were less noticeable in men because of the axial predominance of melanoma occurrence in this sex. The review of 15 earlier studies found by a systematic search of Medline supported the likelihood of our findings. This analysis suggests that ultraviolet radiation has a short-term promotional effect on melanocytes or nevocytes of the limbs, and is not associated with progression from thin to thick melanoma.

Purpose of Review: Epidemiological data have contributed to the classification in 2009 of the full ultraviolet (UV) radiation spectrum as carcinogenic to humans. We reviewed the epidemiological evidence that UVA could be involved in the genesis of cutaneous melanoma., Recent Findings: Use of artificial UV tanning devices (sunbeds) consists mainly of repeated exposure to high UVA doses. Epidemiological studies published over the last years confirmed the association between sunbed use and melanoma. Sunbed use is the most probable cause of an epidemic of melanoma that took place in Iceland from 1990 to 2006. The four-fold increase in melanoma incidence was not followed by an increase in melanoma mortality. Sunscreens were primarily devised for the prevention of sunburn, and UVB is the wavelength causing most sunburns. All observational studies and randomized trials show that sunscreen use may extend sun exposure intended for getting a tan, while it does not necessarily decrease sunburn occurrence. Sunscreen use for tan acquisition would thus lead to similar exposure to UVB and greater exposure to UVA, which could explain the slightly higher melanoma risk often found among sunscreen users., Summary: UVA could be involved in the occurrence of nonlife-threatening melanoma. The increasing use of sunbeds and of sunscreens may partly explain why melanoma incidence increases in most light-skinned populations without concomitant increase in mortality.

Since 1980, sunbed use and travel abroad have dramatically increased in Iceland (64°-66°N). The authors assessed temporal trends in melanoma incidence by body site in Iceland in relation to sunbed use and travel abroad. Using joinpoint analysis, they calculated estimated annual percent changes (EAPCs) and identified the years during which statistically significant changes in EAPC occurred. Between 1954 and 2006, the largest increase in incidence in men was observed on the trunk (EAPC = 4.6%, 95% confidence interval: 3.2, 6.0). In women, the slow increase in trunk melanoma incidence before 1995 was followed by a significantly sharper increase in incidence, mainly among women aged less than 50 years, resembling an epidemic incidence curve (1995-2002: EAPC = 20.4%, 95% confidence interval: 9.3, 32.8). In 2002, the melanoma incidence on the trunk was higher than the incidence on the lower limbs for women. Sunbed use in Iceland expanded rapidly after 1985, mainly among young women, and in 2000, it was approximately 2 and 3 times the levels recorded in Sweden and in the United Kingdom, respectively. Travels abroad were more prevalent among older Icelanders. The high prevalence of sunbed use probably contributed to the sharp increase in the incidence of melanoma in Iceland.

A comprehensive bibliographic search of the literature was conducted to identify studies on Cutaneous Malignant Melanoma (CMM) and non-melanoma skin cancer (NMSC), Vitamin D receptor (VDR) polymorphisms, Vitamin D intake and 25(OH)D serum levels. Fully adjusted risk estimates were found and extracted for the two polymorphisms FokI and BsmI and Vitamin D intake. Ten studies were included in the meta-analysis, with a total of 6805 skin cancer cases. We found an association with CMM for both polymorphisms. The summary relative risks (SRR) for the studies on CMM were: 1.21 (1.03-1.42) and 1.21 (0.95-1.54) for the Ff and ff versus wild-type of FokI, respectively. The SRR for ff versus wild-type became significant with the inclusion of NMSC. The SRR for the studies on CMM were: 0.78 (0.65-0.92) and 0.75 (0.59-0.95) for the Bb and BB versus wild-type of BsmI, respectively. There is also a slight indication of a role of dietary Vitamin D in CMM development. In conclusion, this meta-analysis suggests a possible significant role of VDR FokI and BsmI polymorphism in CMM and NMSC risk. The association with Vitamin D intake is less clear and further studies could be useful to clarify the role of diet.

Mutations in two genes encoding cell cycle regulatory proteins have been shown to cause familial cutaneous malignant melanoma (CMM). About 20% of melanoma-prone families bear a point mutation in the CDKN2A locus at 9p21, which encodes two unrelated proteins, p16(INK4a) and p14(ARF). Rare mutations in CDK4 have also been linked to the disease. Although the CDKN2A gene has been shown to be the major melanoma predisposing gene, there remains a significant proportion of melanoma kindreds linked to 9p21 in which germline mutations of CDKN2A have not been identified through direct exon sequencing. The purpose of this study was to assess the contribution of large rearrangements in CDKN2A to the disease in melanoma-prone families using multiplex ligation-dependent probe amplification. We examined 214 patients from independent pedigrees with at least two CMM cases. All had been tested for CDKN2A and CDK4 point mutation, and 47 were found positive. Among the remaining 167 negative patients, one carried a novel genomic deletion of CDKN2A exon 2. Overall, genomic deletions represented 2.1% of total mutations in this series (1 of 48), confirming that they explain a very small proportion of CMM susceptibility. In addition, we excluded a new gene on 9p21, KLHL9, as being a major CMM gene.

When studying the density of skin lesions, calculations of relative density are based on charts of proportion of skin surface area. However, the current source of information is derived from skewed data obtained at the beginning of the twentieth century. Using more recent data from a population-based sample of children in the United States, we propose a new set of tables. Data from measurements taken in the United States in the 1970s for design and safety were applied to the computer-based model MAN3D. This model, originally created for ergonomic studies in the automotive industry, allowed us to obtain a precise estimate of the main surface areas of children. Compared with previously published studies, our estimates increased the relative proportion of arms and of the trunk and allowed for differentiation of these proportions by sex. New tables are proposed for epidemiological studies of skin lesion density in children.

Epidemiological and biological studies indicate that solar UVB radiation is involved in cutaneous malignant melanoma etiology. Indeed, melanocytes are very frequently exposed to solar UV radiation, which induces cell damage and may promote cell transformation. We previously showed that melanocytes and melanoma cells exposed to UVB radiation activates a p53-independent pathway involving Gadd45a and, more recently, that Gadd45a plays a critical role in UVB-induced G2 cell cycle arrest of melanoma cells. In this study, we demonstrate that the inhibition of UV-induced Gadd45a overexpression by RNA interference results in a dramatic increase of cell death. We identify this cell death as apoptosis, with activation of Caspase-3 and a decrease in Bcl-x(L) expression. Furthermore, we show that inhibition of UV-induced Gadd45a overexpression also leads to increased sensitivity of melanoma cells to therapeutic agents such as DTIC and Cisplatin. We conclude that UVB-induced Gadd45a overexpression protects melanoma cells from apoptosis, both by causing a G2 cell cycle arrest and by inhibiting the mitochondrial apoptotic pathway. These observations suggest that Gadd45a inactivation could be a useful way to sensitize melanoma cells to chemotherapy. JID journal club article: For questions, answers, and open discussion about this article please go to http://network.nature.com/group/jidclub

Sunscreen use is often proposed for sun protection because of their ability to block UV-induced sunburns (the sun protection factor--SPF). Among suntan seekers, however, risk of cutaneous melanoma may be increased because of extended sun exposure duration. We made a systematic review of the evidence linking sunscreen use to sun exposure duration. Five observational studies found that when sun exposure was associated with willingness to get a tan or to stay longer in the sun (i.e., intentional sun exposure), sunscreen use was associated with duration of sun exposure 13-39% longer. Paradoxically, sunburns tend to be more frequent among sunscreen users, probably because of greater natural sun sensitivity. When sun exposure was not intentional, sunscreen use did not increase time spent in the sun. Two European double-blind randomized trials conducted among young sun seekers found daily sun exposure duration, especially sunbathing, 19-25% longer with use of SPF 30 than with use of SPF 10 sunscreens. One randomized trial in a holiday resort in France found a 3-13% increase in sun exposure duration with use of SPF 12 versus SPF 40 sunscreen. But, the SPF 12 groups used 3.6-4.2 more sunscreen than the SPF 40 group, and thus the actual SPF in the SPF 12 group was higher than in the SPF 40 groups. In conclusion, sunscreen use leads to longer duration of sun exposure when sun exposure is intentional, but not when sun exposure is non intentional.

Seasonal variation in cutaneous melanoma incidence with a summer peak is poorly understood. It has been hypothesized to be due to increased diagnosis in summer or a late-promoting effect of sun exposure. We analyzed the characteristics of incident cases of cutaneous melanoma and their outcome by season of diagnosis in the population of New South Wales, Australia. Cases of melanoma (25,845 cases; 10,869 females and 14,976 males) were registered by the New South Wales Central Cancer Registry in 1989 to 1998. There was significant seasonal variation in incidence (P < 0.0001, Nam test). The summer to winter ratio was greater for women, younger people, lesions on the limbs, and superficial spreading melanoma. Melanomas were thicker in winter than in summer (medians 0.75 and 0.70 mm, respectively; P < 0.0001, Kruskal-Wallis test). Cases were followed for a median of 63 months and 2,710 (10.5%) died from their melanoma. Fatality from melanoma was lower for melanomas diagnosed in summer than winter (relative fatality = 0.72; 95% confidence interval, 0.65-0.81); the 5-year survival rate was 92.1% for diagnosis in summer and 89.0% for diagnosis in winter. This result remained significant after adjustment for year of diagnosis, age, sex, Breslow thickness, anatomic location, and histologic type (relative fatality = 0.82; 95% confidence interval, 0.72-0.94). Seasonality in melanoma incidence is probably caused mainly by increased and earlier diagnosis in summer, although a late-stage promotional effect of sun exposure cannot be excluded completely. Earlier diagnosis may also reduce fatality when melanoma is diagnosed in summer. Independence of variation in fatality with season from seasonal variation in thickness, however, suggests that sun exposure around the time of diagnosis decreases fatality of melanoma.

Susceptibility to solar ultraviolet is an important melanoma risk factor. We investigated the relationship between individual susceptibility to ultraviolet and risk of melanoma by measuring the apoptosis triggered in peripheral lymphocytes by a low-dose ultraviolet B irradiation (50 J/m(2)) in young and older melanoma patients and controls. Melanoma patients below the age of 40 are more sensitive to UVB-induced apoptosis than older melanoma patients and healthy controls. Analysis of data (adjusted for age and phototype) shows that UVB-induced apoptosis is an important risk factor for melanoma (OR 9.1, 95% CI [3-28], P=0.0001). UVB-induced apoptosis is independent of phototype (P=0.11, Wald test) and tumour thickness (P=0.88, Spearman correlation, for all cases and 0.26 for patients younger than 40 years), and may be used as a functional laboratory test for studying the genetic-environment interactions involved in melanoma occurrence.

In a large case-control study we found no association between sunbed use and melanoma risk, but indications for potential recall and recruitment biases made the interpretation of the results difficult. Associations with skin phototype (adj OR for skin type I vs. IV: (2.6, 95% CI 1.5-4.8)), hair colour (adj OR red/blond vs. brown/black 2.0 (95% CI 1.4-2.8)) and number of naevi on both arms (OR>10 vs. 10 3.13 (95% CI: 2.47; 3.97)) were comparable to previous studies, but negative associations were found between sun exposure and melanoma risk (adj. OR 0.87 (95% CI: 0.65-1.18)) and in cases between sun exposure and naevus count. These observations led us to speculate that cases may have underreported their sun exposure and, most likely, their sunbed exposure. High percentages of sunbed use among controls indicated possible recruitment bias: eligible controls who were sunbed users were probably more likely to accept the invitation to participate than non-users, possibly due to a feeling of 'guilt' or 'worry' about their habits. Such selective participation may have strongly influenced the risk estimates of sunbed use in our study.

A large European case-control study investigated the association between sunbed use and cutaneous melanoma in an adult population aged between 18 and 49 years. Between 1999 and 2001 sun and sunbed exposure was recorded in 597 newly diagnosed melanoma cases and 622 controls in Belgium, France, The Netherlands, Sweden and the UK. Fifty three percent of cases and 57% of controls ever used sunbeds. The overall adjusted odds ratio (OR) associated with ever sunbed use was 0.90 (95% CI: 0.71-1.14). There was a South-to-North gradient with high prevalence of sunbed exposure in Northern Europe and lower prevalence in the South (prevalence of use in France 20%, OR: 1.19 (0.68-2.07) compared to Sweden, prevalence 83%, relative risk 0.62 (0.26-1.46)). Dose and lag-time between first exposure to sunbeds and time of study were not associated with melanoma risk, neither were sunbathing and sunburns (adjusted OR for mean number of weeks spent in sunny climates >14 years: 1.12 (0.88-1.43); adjusted OR for any sunburn >14 years: 1.16 (0.9-1.45)). Host factors such as numbers of naevi and skin type were the strongest risk indicators for melanoma. Public health campaigns have improved knowledge regarding risk of UV-radiation for skin cancers and this may have led to recall and selection biases in both cases and controls in this study. Sunbed exposure has become increasingly prevalent over the last 20 years, especially in Northern Europe but the full impact of this exposure on skin cancers may not become apparent for many years.

The aim of our study was to analyse seasonal variations in melanoma incidence in Europe. Data from 28117 cutaneous melanoma cases reported during 1978-1993 to the EUROCARE group of registries were analysed. There is a clear summer peak in incidence in Western countries (summer-winter ratio: 1.31 P < 0.0001; Nam's test), which was not observed in Central Europe (ratio: 1.06; P = 0.0699). The amplitude of seasonality is higher for females (ratio = 1.38, 95% Confidence Interval (CI) [1.31-1.44]) than for males (ratio = 1.21 95%CI [1.14-1.29]). It is also higher for upper and lower limbs (1.44 and 1.46, respectively), than for head and neck or trunk regions (1.09 and 1.20, respectively). The amplitude of seasonality also varies with latitude and increases with time: in a linear regression adjusting for age, gender and anatomical localisation, the date of diagnosis was significantly closer to summer solstice with decreasing latitude (P = 0.0005) and for more recent year of diagnosis (P = 0.0123). The effect of latitude on the amplitude of the seasonal variation in melanoma incidence in Europe may be an indicator of ultraviolet B (UVB) exposure. Furthermore, an increase in intentional sun exposure could lead to an increase in melanoma promotion and thus to an increase in the amplitude of seasonal variation.

Background: Since 1950, the greatest increase in cutaneous melanoma incidence in fair-skinned males took place on the trunk and on the head and neck, whereas in females, it took place on the limbs, mainly on the lower limbs. We examined the influence of sex on numbers and size of nevi on different body sites in white European schoolchildren., Methods: Information about each holiday period since birth to interview was recorded from parents of six hundred twenty-eight 6- to 7-year-old children in four European cities (Brussels (Belgium), Bochum (Germany), Lyons (France), and Rome (Italy)). Number and anatomic location of small (2-4.9 mm) and large (>/=5 mm) nevi and individual susceptibility to sunlight were independently assessed., Results: After adjustment for host characteristics, sun exposure, and sun protection habits, males had 7% [95% confidence interval (95% CI), -7 to 19] more small nevi than females. However, compared to females, numbers of small nevi were increased by 17% (95% CI, 1-31) on the head and neck and by 16% (95% CI, 2-27) on the trunk and shoulders. In contrast, in males, the number of small nevi on upper limbs was decreased by -5% (95% CI, -26 to 13), and on lower limbs by -8% (95% CI, -34 to 13). The number of large nevi was 6% higher in males than in females (95% CI, -26 to 30)., Conclusions: The sex differences in small nevus distribution in schoolchildren reflect the sex differences in the anatomic distribution of melanoma in adults. Sex differences in sun exposure behaviors, dressing, and clothing would just add their effects to the sex-dependent inherited propensity to develop nevi on a given body site. These results reinforce the hypothesis by which childhood would be a decisive period for the occurrence of sun-induced biological events implicated in the genesis of cutaneous melanoma.

The objective of this study was to investigate the epidemiology of melanoma across Europe with regard to Breslow thickness and body-site distribution. Incidence data from Cancer Incidence in 5 Continents and the EUROCARE-melanoma database were used: 28?117 melanoma cases from 20 cancer registries in 12 European countries, diagnosed between 1978 and 1992. Regression analysis and general linear modelling were used to analyse the data. Melanomas in Eastern Europe were on average 1.4 mm thicker (P<0.05) than in Western Europe and appeared more often on the trunk. From 1978 to 1992, their Breslow thickness had decreased in Western but not Eastern Europe. There was a latitude gradient in incidence, with highest rates in southern regions in Eastern Europe and an inverse gradient in Western Europe, with highest rates in the North. Mortality:incidence ratios were less favourable in southern parts across Europe, especially in Eastern Europe. If Eastern European populations copy the sunbathing behaviour of the West it is likely that in the near future a higher melanoma incidence can be expected there.