Skin cancers are the most frequent cancers in fair-skinned populations, but we can prevent them.

Cancers of the skin are the most commonly occurring cancers in humans. In fair-skinned populations, up to 95% of keratinocyte skin cancers and 70-95% of cutaneous melanomas are caused by ultraviolet radiation and are thus theoretically preventable. Currently, however, there is no comprehensive global advice on practical steps to be taken to reduce the toll of skin cancer. To address this gap, an expert working group comprising clinicians and researchers from Africa, America, Asia, Australia, and Europe, together with learned societies (European Association of Dermato-Oncology, Euromelanoma, Euroskin, European Union of Medical Specialists, and the Melanoma World Society) reviewed the extant evidence and issued the following evidence-based recommendations for photoprotection as a strategy to prevent skin cancer. Fair skinned people, especially children, should minimise their exposure to ultraviolet radiation, and are advised to use protective measures when the UV index is forecast to reach 3 or higher. Protective measures include a combination of seeking shade, physical protection (e.g. clothing, hat, sunglasses), and applying broad-spectrum, SPF 30 + sunscreens to uncovered skin. Intentional exposure to solar ultraviolet radiation for the purpose of sunbathing and tanning is considered an unhealthy behaviour and should be avoided. Similarly, use of solaria and other artificial sources of ultraviolet radiation to encourage tanning should be strongly discouraged, through regulation if necessary. Primary prevention of skin cancer has a positive return on investment. We encourage policymakers to communicate these messages to the general public and promote their wider implementation.

ICNIRP Statement on Short Wavelength Light Exposure from Indoor Artificial Sources and Human Health.

ABSTRACT: Concerns have been raised about the possibility of effects from exposure to short wavelength light (SWL), defined here as 380-550 nm, on human health. The spectral sensitivity of the human circadian timing system peaks at around 480 nm, much shorter than the peak sensitivity of daytime vision (i.e., 555 nm). Some experimental studies have demonstrated effects on the circadian timing system and on sleep from SWL exposure, especially when SWL exposure occurs in the evening or at night. The International Commission on Non-Ionizing Radiation Protection (ICNIRP) has identified a lack of consensus among public health officials regarding whether SWL from artificial sources disrupts circadian rhythm, and if so, whether SWL-disrupted circadian rhythm is associated with adverse health outcomes. Systematic reviews of studies designed to examine the effects of SWL on sleep and human health have shown conflicting results. There are many variables that can affect the outcome of these experimental studies. One of the main problems in earlier studies was the use of photometric quantities as a surrogate for SWL exposure. Additionally, the measurement of ambient light may not be an accurate measure of the amount of light impinging on the intrinsically photosensitive retinal ganglion cells, which are now known to play a major role in the human circadian timing system. Furthermore, epidemiological studies of long-term effects of chronic SWL exposure per se on human health are lacking. ICNIRP recommends that an analysis of data gaps be performed to delineate the types of studies needed, the parameters that should be addressed, and the methodology that should be applied in future studies so that a decision about the need for exposure guidelines can be made. In the meantime, ICNIRP supports some recommendations for how the quality of future studies might be improved.

Incidence and Factors Associated With Second Primary Invasive Melanoma in Norway.

Importance: Patients diagnosed with a primary melanoma are at high risk of subsequent melanomas. Understanding the risk of second primary invasive melanoma and associated factors is crucial to optimize patient follow-up. Objective: To assess the incidence rate of second primary invasive melanoma and time between the first and second primary invasive melanoma in the Norwegian population. Design, Setting, and Participants: This population-based cohort study included data from deidentified records of all invasive melanomas diagnosed in Norway in 2008 to 2020, obtained from the Cancer Registry of Norway. Data were from adults aged 18 years or older diagnosed with a first primary melanoma. Data analysis was performed from March to August 2023. Main Outcomes and Measures: The main outcome was the incidence rate of second primary invasive melanoma at least 30 days after the first. Accelerated failure time models were fitted to examine potential associations with patient and tumor characteristics. Median time between first and second primary melanomas and 95% CIs were calculated. The likelihood of, and median interval for, second primary melanomas on the same or different site as the first primary were calculated. Results: A total of 19 196 individuals aged 18 years or older were diagnosed with a first primary melanoma. The mean (SD) age at diagnosis of the first primary melanoma was 62 (16) years (range, 18-104 years), and 9763 (51%) were female. The incidence rate in the year following diagnosis was 16.8 (95% CI, 14.9-18.7) per 1000 person-years, which decreased to 7.3 (95% CI, 6.0-8.6) during the second year and stabilized thereafter. Median time between first and second primaries decreased with advancing age and was 37 months (95% CI, 8-49) in patients younger than 40 years, 18 (95% CI, 13-24) in patients aged 50 to 59 years, and 11 (95% CI, 7-18) in patients aged 80 years or older. The second primary was on the same site as their first primary for 47% (359 patients), and on a different site for 53% (407 patients). The median interval until second melanoma on the same site as the initial melanoma was 12 (95% CI, 7-19) months in men and 22 (95% CI, 11-35) months in women. Conclusions and Relevance: Older age and male sex were associated with an increased risk, suggesting that increased surveillance intensity may be considered for men, especially those older than 50 years, for at least 3 years after their initial diagnosis, regardless of the characteristics of their first invasive melanoma.

Cumulative incidence and risk factors for cutaneous squamous cell carcinoma metastases in organ transplant recipients: The Skin Care in Organ Transplant Patients in Europe-International Transplant Skin Cancer Collaborative metastases study, a prospective multicenter study.

INTRODUCTION: Solid organ transplant recipients (SOTRs) are believed to have an increased risk of metastatic cutaneous squamous cell carcinoma (cSCC), but reliable data are lacking regarding the precise incidence and associated risk factors. METHODS: In a prospective cohort study, including 19 specialist dermatology outpatient clinics in 15 countries, patient and tumor characteristics were collected using standardized questionnaires when SOTRs presented with a new cSCC. After a minimum of 2 years of follow-up, relevant data for all SOTRs were collected. Cumulative incidence of metastases was calculated by the Aalen-Johansen estimator. Fine and Gray models were used to assess multiple risk factors for metastases. RESULTS: Of 514 SOTRs who presented with 623 primary cSCCs, metastases developed in 37 with a 2-year patient-based cumulative incidence of 6.2%. Risk factors for metastases included location in the head and neck area, local recurrence, size > 2 cm, clinical ulceration, poor differentiation grade, perineural invasion, and deep invasion. A high-stage tumor that is also ulcerated showed the highest risk of metastasis, with a 2-year cumulative incidence of 46.2% (31.9%-68.4%). CONCLUSIONS: SOTRs have a high risk of cSCC metastases and well-established clinical and histologic risk factors have been confirmed. High-stage, ulcerated cSCCs have the highest risk of metastasis.

Frequency of naevus cells in lymph nodes of melanoma and breast cancer patients.

INTRODUCTION: We aimed to study the frequency (prevalence) and histology of benign melanocytic naevus cells in regional lymph nodes in relation to age and sex and nodal location. MATERIAL AND METHODS: Histopathology reports of sentinel lymph node (SLN) biopsies from melanoma patients, 2002 - 2014, and from breast cancer patients, 2010- 2019, were obtained from records of a single hospital in England. All sections were similarly processed and examined. For standardisation, presence of naevus cells was assessed in a single node per patient: the first SLN biopsied (melanoma) or the node nearest the first SLN (breast cancer). RESULTS: Associations were tested using Fisher's exact test. Naevus cells were found in 10% (60/585) of melanoma patients' index SLNs. Frequency varied significantly by anatomic region: 13% in axillary to 0% cervical SLNs (p = 0.03), but not by sex or age. Within nodes, naevus cells were present in capsular or pericapsular tissue (93%), or trabeculae (7%). In breast cancer patients' index axillary nodes, 6% (11/196) contained naevus cells, all intracapsular. In the predominant 40-69 years age-group, prevalence was similar in breast cancer (7%) and female melanoma (9%) patients, but in those aged 70-100, prevalence was lower in breast cancer (2%) than in female melanoma (15%) patients (p = 0.05). CONCLUSIONS: Standard methods of assessment yielded no clear pattern of naevus cell frequency in lymph nodes by age or sex, but confirmed naevus cell location as mostly intracapsular.

Association of diet quality and weight increase in adult heart transplant recipients.

BACKGROUND: Understanding the quality of the diet of heart transplant recipients (HTRs) is essential to developing effective dietary interventions for weight control, but relevant evidence is scarce. We investigated diet quality and its association with post-transplant increase in weight adjusted for height (body mass index [BMI]) in Australian HTRs. METHODS: We recruited adult HTRs from Queensland's thoracic transplant clinic, 2020-2021. Study participants completed a 3-day food diary using a smart-phone app. Socio-demographic information was collected by self-administered questionnaire, and height, serial weight and clinical information were obtained from medical records. We calculated the Dietary Approaches to Stop Hypertension (DASH) index based on nine food groups and nutrients (index of 90 indicates highest possible quality), and any changes in BMI (≤ 0 kg m-2 or >0 kg m-2) post-transplantation. Median DASH index values were assessed in relation to sex and BMI change using Mann-Whitney U test. RESULTS: Among 49 consented HTRs, 25 (51%) completed the food diary (median age 48 years, 52% females). Median BMI at enrolment was 27.2 kg m-2; median BMI change since transplant was +3.7 kg m-2. Fruit, vegetable, and whole grain intakes were generally lower than recommended, giving a low overall median DASH index of 30 with no sex differences. HTRs for which the BMI increased post-transplant had significantly lower median DASH indices than those whose BMI did not increase (30 vs. 45, p = 0.013). CONCLUSIONS: The diet quality of HTRs appears suboptimal overall, with fruit and vegetable intakes especially low. HTRs whose BMI increased post-transplant had substantially lower quality diets than HTRs whose BMI did not increase.

pSTAT5 is associated with improved survival in patients with thick or ulcerated primary cutaneous melanoma.

Identifying prognostic biomarkers to predict clinical outcomes in stage I and II cutaneous melanomas could guide the clinical application of adjuvant and neoadjuvant therapies. We aimed to investigate the prognostic value of phosphorylated signal transducer and activator of transcription 5 (pSTAT5) as a biomarker in early-stage melanoma. This study evaluated all initially staged Ib and II melanoma patients undergoing sentinel node biopsy at a tertiary centre in Brisbane, Australia between 1994 and 2007, with survival data collected from the Queensland Cancer Registry. Primary melanoma tissue from 189 patients was analysed for pSTAT5 level through immunohistochemistry. Cox regression modelling, with adjustment for sex, age, ulceration, anatomical location, and Breslow depth, was applied to determine the association between pSTAT5 detection and melanoma-specific survival. Median duration of follow-up was 7.4 years. High pSTAT5 detection was associated with ulceration and increased tumour thickness. However, multivariate analysis indicated that high pSTAT5 detection was associated with improved melanoma-specific survival (hazard ratio: 0.15, 95% confidence interval: 0.03-0.67) as compared to low pSTAT5 detection. This association persisted when pSTAT5 detection was limited to immune infiltrate or the vasculature, as well as when sentinel node positivity was accounted for. In this cohort, staining for high-pSTAT5 tumours identified a subset of melanoma patients with increased survival outcomes as compared to low-pSTAT5 tumours, despite the former having higher-risk clinicopathological characteristics at diagnosis. pSTAT5 is likely an indicator of local immune activation, and its detection could represent a useful tool to stratify the risk of melanoma progression.

Prognosis of naevoid melanomas.

INTRODUCTION: There appear to be several variants of naevoid melanoma suspected as having different outcomes, but follow-up studies have been few. We aimed to assess the prognosis of naevoid melanomas in a multi-centre study. MATERIAL AND METHODS: From histopathology records we ascertained patients in the UK, Australia and Italy diagnosed with maturing naevoid melanoma (n = 65; 14; 7 respectively) and nodular/papillomatous naevoid melanoma (12; 6; 0), and patients with superficial spreading melanoma (SSM) from UK (73) and Australia (26). Melanoma deaths in UK patients were obtained from NHS Digital; in Australia, via the National Death Index and cancer registry; and in Italy, through clinical records. For maturing naevoid vs. SSM, we used Cox-proportional hazard regression models to compare survival adjusted for age, sex, tumour thickness, and ulceration, and additionally Fine-Gray regression analysis, to calculate sub-hazard ratios (SHR) in the UK cohort, accounting for competing causes of death. RESULTS: Among UK patients, there was a non-significantly lower risk of melanoma death in maturing naevoid vs SSM, including after accounting for competing causes of death (SHR 0.40, 95% confidence interval (CI) 0.12-1.31), while among nodular/papillomatous naevoid melanoma patients, there were no melanoma deaths on follow-up. Two melanoma deaths occurred in Australian SSM patients, and none in maturing or nodular/papillomatous naevoid melanoma patients, after 5 years' minimum follow-up. None of the 7 Italian patients with maturing naevoid melanoma died of melanoma after nearly 12 years' average follow-up. CONCLUSIONS: There was no significant difference in risk of death from melanomas with naevoid features, and SSM. Nodular/ papillomatous naevoid melanoma patients did not carry higher risk of death than SSM patients though the very few cases of the papillomatous naevoid variant limited our assessment.

Multimodal Transplant-clinic-based Skin Cancer Prevention Education for Organ Transplant Recipients: Feasibility Study.

We studied the feasibility of transplant-clinic staff routinely providing primary prevention advice to lung transplant recipients at high risk of skin cancer. Methods: Patients enrolled by a transplant-clinic study nurse completed baseline questionnaires and received sun-safety brochures. For the 12-mo intervention, transplant physicians were alerted to provide standard sun-protection advice (use of hat, long sleeves, and sunscreen outdoors) by sun-advice prompt cards attached to participants' medical charts at each clinic visit. Patients indicated receiving advice from their physician and from study personnel via an exit-card postclinic, and at final study clinics, they also reported their sun behaviors by questionnaire. Feasibility of the intervention was measured by patients' and clinic staff's study engagement; effectiveness was assessed by calculating odds ratios (ORs) for improved sun protection, using generalized estimating equations. Results: Of 151 patients invited, 134 consented (89%), and 106 (79 %) (63% male, median age 56 y, 93% of European descent) completed the study. Odds of receiving sun advice from transplant physicians and study nurses rose after the intervention compared with baseline (ORs, 1.67; 95% confidence interval [CI], 0.96-2.96 and 3.56; 95% CI, 1.38-9.14, respectively). After 12 mo of regular transplant-clinic advice, odds of sunburn decreased (OR, 0.59; 95% CI, 0.13-2.60), and odds of applying sunscreen (OR, 1.93; 95% CI, 1.20-3.09) almost doubled. Conclusions: Encouragement of primary prevention of skin cancer among organ transplant recipients by physicians and nurses during routine transplant-clinic visits is feasible and appears to be effective.

High-risk Prognostic Tumor Features of Squamous Cell Carcinomas in Organ Transplant Recipients Compared With the General Population.

Importance: The extent to which major high-risk features of squamous cell carcinomas (SCCs) in organ transplant recipients (OTRs) differ from SCCs in the general population is not known. Objective: To quantify the relative frequency of perineural invasion, invasion below the dermis, lack of cellular differentiation, and tumor diameter greater than 20 mm in SCCs in OTRs and the general population, by anatomic site. Design, Setting, and Participants: This dual-cohort study in Queensland, Australia, included a cohort of OTRs at high risk of skin cancer ascertained from 2012 to 2015 (Skin Tumours in Allograft Recipients [STAR] study) and a population-based cohort ascertained from 2011 (QSkin Sun and Health Study). The STAR study comprised population-based lung transplant recipients and kidney and liver transplant recipients at high risk of skin cancer recruited from tertiary centers and diagnosed with histopathologically confirmed SCC from 2012 to 2015. The QSkin participants were recruited from Queensland's general adult population, and primary SCCs diagnosed from 2012 to 2015 were ascertained through Medicare (national health insurance scheme) and linked with histopathology records. Data analysis was performed from July 2022 to April 2023. Main Outcomes and Measures: Prevalence ratio (PR) of head/neck location, perineural invasion, tumor invasion to/beyond subcutaneous fat, poor cellular differentiation, and tumor diameter greater than 20 mm among SCCs in OTRs vs the general population. Results: There were 741 SCCs excised from 191 OTRs (median [IQR] age, 62.7 [56.7-67.1] years; 149 [78.0%] male) and 2558 SCCs from 1507 persons in the general population (median [IQR] age, 63.7 [58.0-68.8] years; 955 [63.4%] male). The SCCs developed most frequently on the head/neck in OTRs (285, 38.6%), but on arms/hands in the general population (896, 35.2%) (P < .001). After adjusting for age and sex, perineural invasion was more than twice as common in OTRs as in population cases (PR, 2.37; 95% CI, 1.70-3.30), as was invasion to/beyond subcutaneous fat (PR, 2.37; 95% CI, 1.78-3.14). Poorly vs well-differentiated SCCs were more than 3-fold more common in OTRs (PR, 3.45; 95% CI, 2.53-4.71), and prevalence of tumors greater than 20 mm vs 20 mm or smaller was moderately higher in OTRs (PR, 1.52; 95% CI, 1.08-2.12). Conclusions and Relevance: In this dual-cohort study, SCCs in OTRs had significantly worse prognostic features than SCCs in the general population, reinforcing the necessity of early diagnosis and definitive management of SCCs in OTRs.

Contribution of skin cancer to overall healthcare costs of lung transplantation in Queensland, Australia.

BACKGROUND: Skin cancers are a major source of morbidity in lung transplant recipients, but the relative costs associated with their treatment are unknown. METHODS: We prospectively followed 90 lung transplant recipients from enrollment in the Skin Tumors in Allograft Recipients study in 2013-2015, until mid-2016. We undertook a cost analysis to quantify the health system costs relating to the index transplant episode and ongoing costs for 4 years. Linked data from surveys, Australian Medicare claims, and hospital accounting systems were used, and generalized linear models were employed. RESULTS: Median initial hospitalization costs of lung transplantation were AU$115,831 (interquartile range (IQR) $87,428-$177,395). In total, 57 of 90 (63%) participants were treated for skin cancers during follow-up at a total cost of AU$44,038. Among these 57, total government costs per person (mostly of pharmaceuticals) over 4 years were median AU$68,489 (IQR $44,682-$113,055) vs AU$59,088 (IQR $38,190-$94,906) among those without skin cancer, with the difference predominantly driven by more doctors' visits, and higher pathology and procedural costs. Healthcare costs overall were also significantly higher in those treated for skin cancers (cost ratio 1.50, 95%CI: 1.09, 2.06) after adjusting for underlying lung disease, age on enrollment, years of immunosuppression, and the number of treated comorbidities. CONCLUSIONS: Skin cancer care is a small component of overall costs. While all lung transplant recipients with comorbidities have substantial healthcare costs, those affected by skin cancer incur even greater healthcare costs than those without, highlighting the importance of skin cancer control.

Nevus Count, Pigmentary Characteristics, and Melanoma-specific Mortality among Norwegian Women with Melanoma >1.0 mm Thick.

Little is known about if and how nevi and pigmentation are associated with melanoma-specific mortality. However, increased melanoma awareness in people with lighter pigmentation and many nevi may result in earlier diagnosis of thinner less-lethal tumors. The aim of this study was to investigate associations between nevus count (asymmetrical > 5 mm and small symmetrical), pigmentary characteristics (hair colour, eye colour, skin colour, freckling, pigmentary score), and melanoma-specific mortality in subjects with melanomas > 1 mm. Data from the Norwegian Women and Cancer cohort, established in 1991, with complete follow-up of melanoma patients until 2018 through the Cancer Registry of Norway, were used to estimate hazard ratios with 95% confidence intervals for the associations between nevus count, pigmentary characteristics, and melanoma-specific mortality, stratified by tumor thickness using Cox regression. Estimated hazard ratios consistently indicated a higher risk of melanoma death for those with darker vs lighter pigmentary characteristics in patients with tumors > 1.0-2.0 mm and > 2.0 mm thick (e.g. pigmentary score hazard ratio 1.25, 95% confidence interval (0.74-2.13)). Among women with melanomas > 1.0 mm thick, lighter pigmentation and asymmetrical nevi may be associated with lower melanoma-specific mortality, suggesting that factors that increase the risk of melanoma may also be associated with decreased risk of death from melanoma.

Conditional survival in patients with stage IB-IIIA melanoma undergoing sentinel node biopsy in Queensland: A longitudinal study.

BACKGROUND: Tumour characteristics such as thickness and ulceration, along with sentinel lymph node (SLN) status, have been essential in predicting survival in patients with locally invasive melanomas at the time of diagnosis. It is unclear if these prognostic factors are relevant 1, 2 or 5 years after diagnosis. OBJECTIVES: The key aim of this project was to analyse conditional survival in a cohort of Queensland patients with stage IB to IIIA melanomas (American Joint Committee on Cancer's staging system, 8th version) and to test the relevance of clinicopathological prognostic factors for melanoma outcome after varying intervals of survival time. METHODS: Patients with primary invasive cutaneous melanoma who were referred to a tertiary melanoma clinic and underwent SLN biopsy between 1994 and 2011 were ascertained. The effect of patient and tumour characteristics on melanoma survival were calculated using multivariate Cox proportional hazard models at diagnosis and at variable times after diagnosis. RESULTS: The final analysis included 651 patients (average age 49 years, 55.5% male) with stage IB to IIIA melanoma. At diagnosis, and after 1 and 2 years survived, SLN positivity, thickness and ulceration were predictive of 10-year survival since diagnosis. However, once patients survived 5 years, only SLN status was predictive. Overall conditional melanoma survival improved with increasing time survived. Five years after diagnosis, 10-year conditional melanoma survival (MSS) was 91% (95% CI 86%-95%) compared with 85% (82%-88%) predicted at diagnosis. The improvement in MSS was observed mainly for Stage II melanoma patients and not for those with a positive SLN biopsy. CONCLUSIONS: This study confirms the improvement of prognosis according to time survived since diagnosis suggesting that after 5 years survival the classic prognostic indicators may not have the same influence.

Prevalence of cataract among Australian commercial airline pilots.

Because little is known about cataract in pilots, we estimated prevalence by anonymously ascertaining all commercial airline pilots diagnosed with cataract 2011-2016 using the electronic Medical Records System of the Australian Civil Aviation Safety Authority. Of 14,163 Australian male commercial pilots licensed in 2011, 1286 aged ≥60 had biennial eye examinations showing a cataract prevalence of 11.6%. Among 12,877 pilots aged <60, based on compulsory eye examinations only when first licensed, prevalence was 0.5%. There was no significant difference by ambient ultraviolet (UV) radiation levels in state of residence though lowest prevalence was seen in the low-UV state of Victoria. Most cataract in pilots ≥60 years was bilateral and of mild severity, while cataract in pilots <60 were more likely to be unilateral and of greater severity.

Reasons for using indoor tanning devices: A systematic review of qualitative evidence.

PURPOSE: Despite the established causal links to skin cancer, skin ageing and eye inflammation, people continue to use indoor tanning devices (hereafter 'sunbeds'). Understanding the reasons underlying the use of sunbeds is essential for developing effective interventions. The purpose of this study was to collate all existing evidence from qualitative papers published to date that had assessed motivations for using sunbeds. METHODS: Six databases were searched from inception to February 2020 for qualitative studies that explored adults' experiences of using sunbeds. Sixteen studies met the inclusion criteria, and a narrative evidence synthesis was used to collate findings from each primary study. RESULTS: Users of sunbeds were motivated primarily by aesthetic concerns but also by perceived psychological benefits (well-being, confidence and 'fitting in') and physical benefits (improvement in skin conditions such as acne, acquiring vitamin D and preventing sunburn). People also chose indoor tanning over alternatives such as fake tans because they considered the alternatives unacceptable and did not consider indoor tanning a serious health risk. To date, no studies have explored alternatives to meeting non-aesthetic needs related to the use of sunbeds. CONCLUSIONS: This comprehensive explanation for the practice of indoor tanning provides the basis for development of complex interventions to reduce the harm caused by using sunbeds. Effective interventions should include promotion of alternatives, such as different methods of relaxing, to satisfy underlying motivations, changing social norms and correcting misperceptions about health benefits.

Use of antihypertensive drugs and risk of cutaneous melanoma: a nationwide nested case-control study.

BACKGROUND: Most antihypertensives can induce dermal photosensitivity, which may increase melanoma risk. However, corroborating evidence is limited. We examined the associations between use of antihypertensives and melanoma risk. METHODS: A nationwide nested case-control study was conducted using data from the Cancer Registry of Norway, the National Registry and the Norwegian Prescription Database in 2004-15. Ten controls were randomly selected for each melanoma case, matched on sex and birth year. The study included 12 048 cases and 117 895 controls. We estimated rate ratios (RRs) with 95% confidence intervals (CIs). All analyses were adjusted for ambient ultraviolet radiation (UVR). We additionally performed active comparator analyses, and sensitivity analyses by only including new users, distinguishing between exclusive and mixed users, allowing for different latency periods, and subgroup analyses by melanoma subtype and clinical stage. RESULTS: Compared with non-use, we observed a slightly increased melanoma risk in users of diuretics (RR 1.08, CI 1.01-1.15), calcium-channel blockers (RR 1.10, CI 1.04-1.18) and drugs affecting the renin-angiotensin system (RR 1.10, CI 1.04-1.16), but not for beta blockers (RR 0.97, CI 0.92-1.03). We found no heterogeneity of associations by melanoma subtype or clinical stage and no dose-response relationship between the cumulative defined daily doses (DDDs) and melanoma. No interaction was found between cumulative DDDs and ambient UVR. CONCLUSIONS: Weak associations, with lack of a dose-response relationship and lack of interactions with ambient UVR, in the DDD analysis in this nationwide study do not support a causal relationship between antihypertensives and melanoma risk.