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OBJECTIVES: Observational studies have suggested that a higher 25-hydroxyvitamin D concentration may be associated with longer telomere length; however, this has not been investigated in randomised controlled trials. We conducted an ancillary study within a randomised, double-blind, placebo-controlled trial of monthly vitamin D (the D-Health Trial) for the prevention of all-cause mortality, conducted from 2014 to 2020, to assess the effect of vitamin D supplementation on telomere length (measured as the telomere to single copy gene (T/S) ratio). DESIGN, SETTING, PARTICIPANTS, AND INTERVENTION: Participants were Australians aged 60-84 years and we randomly selected 1,519 D-Health participants (vitamin D: n=744; placebo: n=775) for this analysis. We used quantitative polymerase chain reaction to measure the relative telomere length (T/S ratio) at 4 or 5 years after randomisation. We compared the mean T/S ratio between the vitamin D and placebo groups to assess the effect of vitamin D supplementation on relative telomere length, using a linear regression model with adjustment for age, sex, and state which were used to stratify the randomisation. RESULTS: The mean T/S ratio was 0.70 for both groups (standard deviation 0.18 and 0.16 for the vitamin D and placebo groups respectively). The adjusted mean difference (vitamin D minus placebo) was -0.001 (95% CI -0.02 to 0.02). There was no effect modification by age, sex, body mass index, or predicted baseline 25-hydroxyvitamin D concentration. CONCLUSION: In conclusion, routinely supplementing older adults, who are largely vitamin D replete, with monthly doses of vitamin D is unlikely to influence telomere length.
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Vitamina D , Vitaminas , Humanos , Anciano , Australia , Vitaminas/farmacología , Vitaminas/uso terapéutico , Calcifediol , Telómero , Suplementos Dietéticos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Among the histogenic subtypes of melanoma, nodular melanoma (NM) is the major contributor for thicker and fatal melanomas and it has been associated with melanoma-specific death in thin tumours, highlighting an important subgroup of 'aggressive thin' melanomas. This review provides a synthesis of the distinct characteristics of NM, with respect to epidemiology and risk factors, clinical presentation, histopathology, molecular and dermoscopic aspects, and screening practices. The real challenges are to find better biomarkers of aggressiveness and to know whether the control of such aggressive melanomas can be influenced by targeted interventions such as early detection, drug interventions and preventive strategies.
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Melanoma , Neoplasias Cutáneas , Diagnóstico Precoz , Humanos , Factores de RiesgoRESUMEN
OBJECTIVES: The major cause of mucosal squamous cell carcinomas of the head and neck (HNSCCs) has been attributed to human papillomavirus (HPV) infection. Here we investigate if microRNA expression in HNSCC can be used as a prognostic tool with or without HPV status. MATERIALS AND METHODS: We performed a discovery miRNA microarray (miRBase v.21) profiling of 52 tonsillar SCCs with TaqMan real-time PCR validation of 228 HNSCCs. Patients had a histologically confirmed primary SCC of the oropharynx, oral cavity, hypopharynx or larynx. Logistic regression models were used to estimate the magnitude of the effect of association with clinical factors and miRNAs associated with HPV status. For recurrence and survival analysis, we used unadjusted and multivariable adjusted Cox proportional hazard regression models. RESULTS: Seventeen miRNAs were significantly associated with better prognosis in the discovery phase and were validated in the extended dataset. The best fitting model (AUC = 0.92) for HPV status included age, smoking, and miRNAs: miR-15b, miR-20b, miR-29a, miR-29c, miR-142, miR-146a and miR-205. Using Cox regression model for recurrence, miR-29a was associated with 49% increased risk of recurrence while miR-30e and miR-342 were associated with decreased risk of recurrence with HRs 0.92 (95% CI 0.85-0.99) and 0.84 (95% CI 0.73-0.98), respectively. Our best fitting model for survival included age, gender, alcohol consumption, N stage, recurrence, HPV status, together with miRNAs-20b, 29a, and 342. CONCLUSION: miRNAs show potential to serve as usual biomarkers to predict the clinical course of patients with mucosal HNSCC.
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MicroARNs/metabolismo , Papillomaviridae/patogenicidad , Carcinoma de Células Escamosas de Cabeza y Cuello/virología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/patologíaRESUMEN
Individual studies have suggested that the association between occupational exposure to solar ultraviolet radiation (UVR) and the development of keratinocyte cancers (KCs) may only be valid in populations of European ancestry living in certain geographical regions. Comparative global data are scarce and so this review aimed to summarize current evidence on the association between occupational exposure to solar UVR and the development of KCs, with a specific focus on geographical location and skin colour. Ovid MEDLINE, PubMed, Embase and Web of Science were searched for potentially relevant records. Extracted data were summarized by study, country and region. We included one prospective cohort study and 18 case-control studies (n = 15 233) from 12 countries in regions where the majority of the population is white skinned (Americas, Europe and Oceania). Eighteen of the 19 studies reported effect estimates suggesting an increased risk of basal cell carcinoma (BCC) and/or squamous cell carcinoma (SCC) among outdoor workers. Only 11 studies found a significantly increased risk and many had imprecise estimates. There was a significantly increased risk of BCC and SCC in individual studies in North America, Latin America and the Caribbean, Western Europe and Southern Europe, but not across regions or countries. Overall, 95% of studies reported higher risks among outdoor workers, although the increases in risk were statistically significant in just over half of the studies. Well-designed and sufficiently powered occupational case-control and cohort studies with adequate adjustment for confounding factors and other risk factors are required to provide more accurate risk estimates for occupational KC.
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Carcinoma Basocelular , Enfermedades Profesionales , Exposición Profesional , Neoplasias Cutáneas , Carcinoma Basocelular/epidemiología , Carcinoma Basocelular/etiología , Región del Caribe , Europa (Continente)/epidemiología , Humanos , Queratinocitos , América del Norte , Exposición Profesional/efectos adversos , Estudios Prospectivos , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/etiología , Luz Solar/efectos adversos , Rayos Ultravioleta/efectos adversosRESUMEN
BACKGROUND: Screening for skin cancer can be cost-effective if focused on high-risk groups. Risk prediction tools have been developed for keratinocyte cancers and melanoma to optimize advice and management. However, few have been validated in a clinical setting over the past few years. OBJECTIVES: To assess the clinical utility of risk assessment tools to identify individuals with prevalent skin cancers in a volunteer-based screening clinic. METHODS: Participants were adults presenting for a skin check at a volunteer-based skin cancer screening facility. We used previously published tools, based on questionnaire responses, to predict melanoma and keratinocyte cancers [KCs; basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)] and classified each participant into one of five risk categories. Participants subsequently underwent a full skin examination by a dermatologist. All suspicious lesions were biopsied, and all cancers were histopathologically confirmed. RESULTS: Of 789 people who presented to the clinic, 507 (64%) consented to the study. Twenty-two BCCs, 19 SCCs and eight melanomas were diagnosed. The proportion of keratinocyte cancers diagnosed increased according to risk category from <1% in the lowest to 24% in the highest risk category (P < 0.001). Subtype analysis revealed similar proportionate increases in BCC or SCC prevalence according to risk category. However, a similar proportion of melanoma cases were detected in the low-risk and high-risk groups. CONCLUSION: The risk prediction model for keratinocyte cancers can reliably identify individuals with a significant skin cancer burden prior to a skin examination in the community setting. The prediction tool for melanoma needs to be tested in a larger sample exposed to a wider range of environmental risk factors.
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Carcinoma Basocelular , Melanoma , Neoplasias Cutáneas , Adulto , Carcinoma Basocelular/diagnóstico , Carcinoma Basocelular/epidemiología , Detección Precoz del Cáncer , Humanos , Melanoma/diagnóstico , Melanoma/epidemiología , Factores de Riesgo , Sensibilidad y Especificidad , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/epidemiologíaRESUMEN
BACKGROUND: Lung transplant recipients are at high risk of skin cancer, but precise annual incidence rates of treated skin cancers per patient are unknown. OBJECTIVES: To perform a prospective assessment of the total burden of histologically confirmed squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) and associated factors in lung transplant recipients. METHODS: A population-based cohort of 125 Queensland lung transplant recipients aged 18 years and over, recruited between 2013 and 2015, were followed to the end of 2016. All underwent dermatological skin examinations at baseline and annually thereafter and patients self-reported all interim treated skin cancers, which were verified against pathology databases. Standard skin cancer risk factors were obtained via questionnaire, and details of medications were acquired from hospital records. RESULTS: During a median follow-up time of 1·7 years, 29 (23%) and 30 (24%) lung transplant recipients with a median duration of immunosuppression of 3·3 years developed SCC and BCC, respectively. The general population age-standardized incidence rates of SCC and BCC were 201 and 171 per 1000 person-years, respectively (based on first primary SCC or BCC during follow-up); however, on accounting for multiple primary tumours, corresponding incidence rates were 447 and 281 per 1000 person-years. Risk of multiple SCCs increased around sixfold in those aged ≥ 60 years and in those with previous skin cancer, and increased around threefold in those treated with the antifungal medication voriconazole. Multiple BCC risk rose threefold from age 60 years and tenfold for patients with previous skin cancer. CONCLUSIONS: Lung transplant recipients have very high incidence of multiple primary skin cancers. Close surveillance and assiduous prevention measures are essential. Linked Comment: Proby and Harwood. Br J Dermatol 2020; 183:416-417.
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Carcinoma Basocelular , Neoplasias Cutáneas , Adolescente , Adulto , Anciano , Carcinoma Basocelular/epidemiología , Humanos , Incidencia , Pulmón , Persona de Mediana Edad , Estudios Prospectivos , Queensland/epidemiología , Factores de Riesgo , Neoplasias Cutáneas/epidemiología , Receptores de TrasplantesRESUMEN
BACKGROUND: Thin cutaneous melanomas (≤ 1·00 mm) are increasing worldwide, causing around a quarter of all melanoma deaths in the U.S.A. and Australia. Identification of predictive factors for potentially fatal thin melanomas could allow better use of resources for follow-up. OBJECTIVES: To identify the clinicopathological factors associated with fatal thin melanomas. METHODS: This large, nested case-case study extracted data from the population-based Queensland Cancer Registry, Australia. Our cohort consisted of Queensland residents aged 0-89 years who were diagnosed with a single, locally invasive thin melanoma (≤ 1·00 mm) between 1995 and 2014. Fatal cases (eligible patients who died from melanoma) were individually matched to three nonfatal cases (eligible patients who were not known to have died from melanoma) according to sex, age, year of diagnosis and follow-up interval. Using conditional logistic regression, we calculated odds ratios (ORs) for melanoma-specific death, adjusting for all collected clinicopathological variables. RESULTS: In the cohort, 27 660 eligible patients were diagnosed with a single, thin melanoma. The final case-case series included 424 fatal cases and 1189 nonfatal cases. Fatal cases were sixfold as likely to arise on the scalp as on the back [OR 6·39, 95% confidence interval (CI) 2·57-15·92] and six times as likely to be of thickness 0·80-1·00 mm as of < 0·30 mm (OR 6·00, 95% CI 3·55-10·17). CONCLUSIONS: Scalp location is a strong prognostic factor of death from thin melanoma. Further, this study provides support that melanomas with a thickness of 0·80-1·00 mm are the more hazardous thin lesions. Patients with these tumour characteristics require specific attention during follow-up. What's already known about this topic? Thin invasive melanomas (≤ 1·00 mm) contribute a substantial proportion of melanoma fatalities, owing to the high volume of disease. There is a need to find prognostic factors that will better identify fatal thin melanomas at the time of diagnosis. What does this study add? In this large population-based study, fatal thin tumours were sixfold as likely to be located on the scalp as on the back. Thin melanomas of 0·80-1·00 mm thickness were six times as likely to be associated with death as tumours < 0·30 mm. Scalp location and increasing thickness are strong predictive factors of fatal thin melanomas, indicating that patients with these tumour characteristics require close follow-up.
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Melanoma , Neoplasias Cutáneas , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Australia/epidemiología , Niño , Preescolar , Humanos , Lactante , Recién Nacido , Persona de Mediana Edad , Oportunidad Relativa , Pronóstico , Queensland/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Melanoma develops as the result of complex interactions between sun exposure and genetic factors. However, data on these interactions from prospective studies are scant. OBJECTIVES: To quantify the association between ambient and personal ultraviolet exposure and incident melanoma in a large population-based prospective study of men and women residing in a setting of high ambient ultraviolet radiation, and to examine potential gene-environment interactions. METHODS: Data were obtained from the QSkin Sun and Health Study, a prospective cohort study of men and women aged 40-69 years, randomly sampled from the Queensland population in 2011. Participants were genotyped and assessed for ultraviolet exposure. RESULTS: Among participants with genetic data (n = 15 373), 420 (2·7%) developed cutaneous melanoma (173 invasive, 247 in situ) during a median follow-up time of 4·4 years. Country of birth, age at migration, having > 50 sunburns in childhood or adolescence, and a history of keratinocyte cancer or actinic lesions were significantly associated with melanoma risk. CONCLUSIONS: An interaction with polygenic risk was suggested: among people at low polygenic risk, markers of cumulative sun exposure (as measured by actinic damage) were associated with melanoma. In contrast, among people at high polygenic risk, markers of high-level early-life ambient exposure (as measured by place of birth) were associated with melanoma (hazard ratio for born in Australia vs. overseas 3·16, 95% confidence interval 1·39-7·22). These findings suggest interactions between genotype and environment that are consistent with divergent pathways for melanoma development. What's already known about this topic? The relationship between sun exposure and melanoma is complex, and exposure effects are highly modified by host factors and behaviours. The role of genotype on the relationship between ultraviolet radiation exposure and melanoma risk is poorly understood. What does this study add? We found that country of birth, age at migration, sunburns in childhood or adolescence, and history of keratinocyte cancer or actinic lesions were significantly associated with melanoma risk, while other measures of continuous or more intermittent patterns of sun exposure were not. We found evidence for gene-environment interactions that are consistent with divergent pathways for melanoma development. Linked Comment: Cust. Br J Dermatol 2020; 183:205-206. Plain language summary available online.
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Melanoma , Neoplasias Cutáneas , Adulto , Anciano , Australia/epidemiología , Femenino , Humanos , Masculino , Melanoma/etiología , Melanoma/genética , Persona de Mediana Edad , Estudios Prospectivos , Queensland/epidemiología , Factores de Riesgo , Neoplasias Cutáneas/etiología , Neoplasias Cutáneas/genética , Luz Solar/efectos adversos , Rayos Ultravioleta/efectos adversosAsunto(s)
Aspirina , Neoplasias Cutáneas , Antiinflamatorios no Esteroideos , Australia , Estudios de Cohortes , Humanos , QueratinocitosRESUMEN
BACKGROUND: Sunscreen use can prevent skin cancer, but there are concerns that it may increase the risk of vitamin D deficiency. OBJECTIVES: We aimed to review the literature to investigate associations between sunscreen use and vitamin D3 or 25 hydroxyvitamin D [25(OH)D] concentration. METHODS: We systematically reviewed the literature following the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. We identified manuscripts published in English between 1970 and 21 November 2017. Eligible studies were experimental [using an artificial ultraviolet radiation (UVR) source], field trials or observational studies. The results of each of the experimental studies and field trials are described in detail. Two authors extracted information from observational studies, and applied quality scoring criteria that were developed specifically for this question. These have been synthesized qualitatively. RESULTS: We included four experimental studies, three field trials (two were randomized controlled trials) and 69 observational studies. In the experimental studies sunscreen use considerably abrogated the vitamin D3 or 25(OH)D production induced by exposure to artificially generated UVR. The randomized controlled field trials found no effect of daily sunscreen application, but the sunscreens used had moderate protection [sun protection factor SPF) ~16]. The observational studies mostly found no association or that self-reported sunscreen use was associated with higher 25(OH)D concentration. CONCLUSIONS: There is little evidence that sunscreen decreases 25(OH)D concentration when used in real-life settings, suggesting that concerns about vitamin D should not negate skin cancer prevention advice. However, there have been no trials of the high-SPF sunscreens that are now widely recommended. What's already known about this topic? Previous experimental studies suggest that sunscreen can block vitamin D production in the skin but use artificially generated ultraviolet radiation with a spectral output unlike that seen in terrestrial sunlight. Nonsystematic reviews of observational studies suggest that use in real life does not cause vitamin D deficiency. What does this study add? This study systematically reviewed all experimental studies, field trials and observational studies for the first time. While the experimental studies support the theoretical risk that sunscreen use may affect vitamin D, the weight of evidence from field trials and observational studies suggests that the risk is low. We highlight the lack of adequate evidence regarding use of the very high sun protection factor sunscreens that are now recommended and widely used.
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Neoplasias Cutáneas/prevención & control , Piel/efectos de los fármacos , Protectores Solares/efectos adversos , Deficiencia de Vitamina D/epidemiología , Vitamina D/análogos & derivados , Administración Cutánea , Humanos , Estudios Observacionales como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo/estadística & datos numéricos , Autoinforme/estadística & datos numéricos , Piel/metabolismo , Piel/efectos de la radiación , Neoplasias Cutáneas/etiología , Factor de Protección Solar , Luz Solar/efectos adversos , Protectores Solares/administración & dosificación , Protectores Solares/química , Rayos Ultravioleta/efectos adversos , Vitamina D/análisis , Vitamina D/metabolismo , Deficiencia de Vitamina D/diagnóstico , Deficiencia de Vitamina D/etiologíaRESUMEN
BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been postulated as chemopreventive agents for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), but findings from observational studies have been inconsistent, and clinical trial data are scant. OBJECTIVES: To examine the association between aspirin and NSAID (nonaspirin) use and the risk of BCC and SCC in a large cohort specifically designed for skin cancer outcomes. METHODS: We used data from the QSkin Study, a prospective cohort of 43 764 residents of Queensland, Australia (34 630 were included in this study and 23 581 were used in our primary analyses). We used Cox proportional hazards models to estimate the hazard ratios (HRs) between self-reported aspirin and NSAID use 1 year prior to study baseline and the first histologically confirmed BCC or SCC for high-risk (history of skin cancer excisions or more than five actinic lesions treated) and average-to-low-risk participants (no history of skin cancer excision and at most five actinic lesions treated). RESULTS: After a median of 3 years of follow-up, 3421 participants developed BCC and 1470 SCC (2288 BCC and 932 SCC with complete covariate information). Among the high-risk group (1826 BCC and 796 SCC), compared with never use, frequent (at least weekly) NSAID use was associated with reduced risk of BCC (HR 0·84, 95% confidence interval 0·71-0.99) but not SCC. Aspirin use was associated with reduced risk of SCC (HR 0·77, 95% confidence interval 0·64-0·93) only among infrequent (less than weekly) users and was not associated with BCC. We observed no association between NSAID or aspirin use and the risk of BCC or SCC among average-to-low-risk participants. CONCLUSIONS: While some weakly inverse associations were observed between prior use of aspirin or NSAIDs and skin cancer, the inconsistent patterns of associations do not provide convincing evidence that these medications reduce subsequent skin cancer risk. Further data on doses, duration and long-term follow-up may help us to comprehend the cumulative dose effect.
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Antiinflamatorios no Esteroideos/uso terapéutico , Aspirina/uso terapéutico , Carcinoma Basocelular/epidemiología , Carcinoma de Células Escamosas/epidemiología , Neoplasias Cutáneas/epidemiología , Adulto , Anciano , Carcinoma Basocelular/prevención & control , Carcinoma de Células Escamosas/prevención & control , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Queensland/epidemiología , Factores de Riesgo , Neoplasias Cutáneas/prevención & controlRESUMEN
BACKGROUND: Ultraviolet radiation causes cutaneous melanoma. Sunscreen prevents sunburn and protects skin cells against mutations. High-quality epidemiological studies suggest regular sunscreen use prevents melanoma. OBJECTIVES: To calculate the potential impact fraction (PIF) for melanoma in the U.S.A. and Australia assuming a range of different intervention scenarios intended to increase sunscreen use. METHODS: We calculated the PIF, the proportional difference between the observed number of melanomas arising under prevailing levels of sunscreen use compared with the number expected under counterfactual scenarios. We used published melanoma incidence projections for Australia and the white population in the U.S.A. from 2012 through to 2031 as the baseline condition, with estimates for protective effects of 'regular sunscreen use' from the literature. Sunscreen prevalence was sourced from national or state surveys. RESULTS: Under a plausible public health intervention scenario comprising incremental increases in sunscreen prevalence over a 10-year implementation programme, we estimated that cumulatively to 2031, 231 053 fewer melanomas would arise in the U.S. white population (PIF 11%) and 28 071 fewer melanomas would arise in Australia (PIF 10%). Under the theoretical maximum model of sunscreen use, almost 797 000 (PIF 38%) and approximately 96 000 (PIF 34%) melanomas would be prevented in the U.S.A. and Australia, respectively between 2012 and 2031. A sensitivity analysis using weaker effect estimates resulted in more conservative PIF estimates. CONCLUSIONS: Overall, interventions to increase use of sunscreen would result in moderate reductions in melanoma incidence, assuming no compensatory overexposure to the sun. Countries with a high incidence of melanoma should monitor levels of sunscreen use in the community.
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Melanoma/prevención & control , Neoplasias Inducidas por Radiación/prevención & control , Neoplasias Cutáneas/prevención & control , Protectores Solares/uso terapéutico , Adolescente , Adulto , Anciano , Australia/epidemiología , Niño , Femenino , Humanos , Incidencia , Masculino , Melanoma/epidemiología , Persona de Mediana Edad , Neoplasias Inducidas por Radiación/epidemiología , Prevalencia , Factores de Riesgo , Distribución por Sexo , Neoplasias Cutáneas/epidemiología , Estados Unidos/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Mobile teledermoscopy allows consumers to send images of skin lesions to a teledermatologist for remote diagnosis. Currently, technology acceptance of mobile teledermoscopy by people at high risk of melanoma is unknown. OBJECTIVES: We aimed to determine the acceptance of mobile teledermoscopy by consumers based on perceived usefulness, ease of use, compatibility, attitude/intention, subjective norms, facilitators and trust before use. Consumer satisfaction was explored after use. METHODS: Consumers aged 50-64 years at high risk of melanoma (fair skin or previous skin cancer) were recruited from a population-based cohort study and via media announcements in Brisbane, Australia in 2013. The participants completed a 27-item questionnaire preteledermoscopy modified from a technology acceptance model. The first 49 participants with a suitable smartphone then conducted mobile teledermoscopy in their homes for early detection of melanoma and were asked to rate their satisfaction. RESULTS: The preteledermoscopy questionnaire was completed by 228 participants. Most participants (87%) agreed that mobile teledermoscopy would improve their skin self-examination performance and 91% agreed that it would be in their best interest to use mobile teledermoscopy. However, nearly half of participants (45%) were unsure about whether they had complete trust in the telediagnosis. The participants who conducted mobile teledermoscopy (n = 49) reported that the dermatoscope was easy to use (94%) and motivated them to examine their skin more often (86%). However, 18% could not take photographs in hard-to-see areas and 35% required help to submit the photograph to the teledermatologist. CONCLUSIONS: Mobile teledermoscopy consumer acceptance appears to be favourable. This new technology warrants further assessment for its utility in the early detection of melanoma or follow-up.