LIFETIME AMBIENT ULTRAVIOLET RADIATION EXPOSURE AND INCIDENCE OF AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To investigate the link between lifelong exposure to ultraviolet radiation (UVR) and the development of age-related macular degeneration (AMD). METHODS: The Alienor study is a prospective population-based cohort involving 963 residents of Bordeaux, France, older than 73 years. A subset of 614 participants for advanced AMD and 422 participants for early AMD were included in the analysis. The participants' residential history combined with UVR estimates from the EuroSun satellite were used to estimate the amount of ambient UVR they have been exposed to over their lifetime. Age-related macular degeneration was classified from retinal fundus photographs and spectral domain optical coherence tomography at 2 to 3 years intervals over the 2006 to 2017 period. Associations between cumulative exposure to ultraviolet A, ultraviolet B, and total (total UV) and the incidence of early and advanced AMD were estimated using multivariate Cox models. RESULTS: Intermediate quartiles of total UV, ultraviolet A, and ultraviolet B exposures were associated with a higher risk for incident early AMD (Hazard Ratio [HR] =2.01 [95% confidence interval [CI] = 1.27-3.13], HR = 2.20 [95% CI = 1.38-3.50], HR = 1.79 [95% CI = 1.13-2.80], respectively) as compared with the lower quartile. However, this risk did not further increase in the highest quartiles of exposure. None of the three types of UVR exposure was significantly associated with incident advanced AMD. CONCLUSION: Despite an increased risk with intermediate compared with low UVR exposure, our study cannot confirm a dose-response relationship of UVR exposure with early AMD onset.

Health disturbances and exposure to radiofrequency electromagnetic fields from mobile-phone base stations in French urban areas.

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.

Radiofrequency exposure of people living near mobile-phone base stations in France.

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.

Invited Commentary: Indoor Tanning-A Melanoma Accelerator?

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.

Residential exposure to ultraviolet light and risk of precursor B-cell acute lymphoblastic leukemia: assessing the role of individual risk factors, the ESCALE and ESTELLE studies.

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/cm2 compared to UV ≤ 105.5 J/cm2. 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.

UV Driven Tanning Salons: Danger on Main Street.

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/m2, 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.

Residential exposure to solar ultraviolet radiation and incidence of childhood hematological malignancies in France.

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.

Tanning salons and skin cancer.

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.

Epidemiological evidence that UVA radiation is involved in the genesis of cutaneous 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.

Erythemal and vitamin D weighted solar UV dose-rates and doses estimated from measurements in mainland France and on Réunion Island.

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.

A melanoma epidemic in Iceland: possible influence of sunbed use.

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.

Ultraviolet radiation and cutaneous melanoma: a historical perspective.

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 contribution of large genomic deletions at the CDKN2A locus to the burden of familial melanoma.

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.

Variation in incidence and fatality of melanoma by season of diagnosis in new South Wales, Australia.

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.

Ultraviolet B sensitivity of peripheral lymphocytes as an independent risk factor for cutaneous 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.

Seasonal variation in the occurrence of cutaneous melanoma in Europe: influence of latitude. An analysis using the EUROCARE group of registries.

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.

A multicentre epidemiological study on sunbed use and cutaneous melanoma in Europe.

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.

Anatomical UV Exposure in French Outdoor Workers.

BACKGROUND: Solar ultraviolet has been recognized as the main causative factor for skin cancer and is currently classified as a carcinogenic agent by International Agency for Research on Cancer. METHOD: Results from a previous phone survey conducted in 2012 in France were used to assess exposure conditions to sun among outdoor workers. Satellite data were used in combination with an exposure model to assess anatomical exposure. RESULT: The yearly median exposure of the outdoor worker population is 77  kJ/m2 to 116  kJ/m2. Road workers, building workers, and gardeners are the more exposed. About 70% of the yearly dose estimate is due to the cumulative summer and spring exposures. CONCLUSIONS: This study highlights the role of individual factors in anatomical exposure and ranks the most exposed body parts and outdoor occupations. Prevention messages should put emphasis on spring exposure, which is an important contributor to the yearly dose.