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With the ongoing progress of basic research along with the introduction of new pharmaceutical options spanning almost all therapeutic areas, the need for biomarkers that will be implemented into the personalized medical approach is higher than ever. Their use can be incorporated into clinical practice and can be applied to the classification of disorders and the evaluation of disease severity but also to the monitoring of the progress of therapeutic/pharmaceutical interventions. This systematic review collects the findings of hematologic biomarkers in various cutaneous malignancies, excluding malignant melanoma, to support their potential use in the prognosis but also in the assessment of therapeutic strategies for the specific category of skin disorders.
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Keratinocyte skin cancer, consisting of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), is by far the most common cancer in white-skinned populations, with rapid increases over the last 50 years. While the age-standardized incidence rates increase worldwide, the age-standardized mortality rates are variable. The incidence rates of keratinocyte skin cancer are much higher compared to those of melanoma, and are largely attributed to the raising exposure to ultraviolet (UV) radiation, the most important causal risk factor for skin cancer. Whereas the development of BCC is mainly due to intense UV exposure during childhood and adolescence, the development of SCC is related to chronic, cumulative UV exposure over decades. Although mortality rates are relatively low, SCC is an increasing problem for healthcare services, significantly causing morbidity, especially in older age groups. This review reports on the epidemiology of keratinocyte skin cancer, with a focus on SCC, in Australia, the United States, and the north of Europe, with an outlook on further challenges health systems will be confronted with in the next 20 years.
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Previous observational studies have indicated an association between hair color and the risk of melanoma and keratinocyte skin cancer (KSC); however, different hair colors show inconsistent effects on skin cancers. Here, we conducted a two-sample Mendelian randomization (MR) study to evaluate the causal relationship between natural hair color and skin cancers by using 211 single nucleotide polymorphisms as genetic instruments from a genome-wide meta-analysis of 360,270 individuals of European ancestry. Light hair colors (red, blonde, and light brown) were associated with high levels of cutaneous melanoma (CM) and KSC (CM-inverse variance weighted [IVW] odds ratio [OR]-red: 1.034, 95% confidence interval [CI]: 1.025-1.044, P < 0.001; OR-blonde: 1.008, 95% CI: 1.003-1.014, P = 0.003; OR-light brown: 1.006, 95% CI: 1.002-1.011, P = 0.009; KSC-IVW OR-red: 1.078, 95% CI: 1.053-1.103, P < 0.001; OR-blonde: 1.024, 95% CI: 1.009-1.040, P = 0.002; OR-light brown: 1.018, 95% CI: 1.004-1.033, P = 0.01). However, dark brown hair showed an inverse causal relationship with skin cancers (CM IVW OR: 0.987, 95% CI: 0.984-0.990, P < 0.001; KSC IVW OR: 0.979, 95% CI: 0.970-0.988, P < 0.001). Black hair was associated with a decreased risk of KSC (IVW OR: 0.954, 95% CI: 0.913-0.997, P = 0.036) but showed no causal relationship with CM. The present study provides strong MR evidence of a causal association between hair color and skin cancer. Secondary MR analyses enhances result robustness by replicating findings, exploring gender-specific effects, and providing a more comprehensive understanding of the complex relationship between hair color and skin cancers. More large-scale MR studies or randomized controlled trials are required to further investigate the mechanisms of the association between hair color and skin cancers.
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Melanoma , Neoplasias Cutáneas , Humanos , Neoplasias Cutáneas/genética , Melanoma/genética , Color del Cabello/genética , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Estudio de Asociación del Genoma Completo , Melanoma Cutáneo MalignoRESUMEN
BACKGROUND: The Black population has lower skin cancer incidence compared to White, Indian/Asian, and Mixed-race populations in South Africa; however, skin cancer still exists in the Black population. The aim of this study is to identify risk factors associated with skin cancer among Black South Africans. MATERIALS AND METHODS: A case-control study was conducted. Cases were patients with keratinocyte cancers (KCs) and/or melanoma skin cancers (MSCs) and controls were cardiovascular patients. Sociodemographic exposures, environmental health variables, smoking, and HIV status were assessed. Stepwise logistic regression was used to identify risk factors associated with KCs and MSCs. RESULTS: The KCs histological subtypes showed that there were more squamous cell carcinomas (SCCs) (78/160 in females, and 72/160 in males) than basal cell carcinomas (BCCs). The SCC lesions were mostly found on the skin of the head and neck in males (51%, 38/72) and on the trunk in females (46%, 36/78). MSC was shown to affect the skin of the lower limbs in both males (68%, 27/40) and females (59%, 36/61). Using females as a reference group, when age, current place of residency, type of cooking fuel used, smoking, and HIV status were adjusted for, males had an odds ratio (OR) of 2.04 for developing KCs (confidence interval [CI]: 1.08-3.84, p = .028). Similarly, when age, current place of residency, and place of cooking (indoors or outdoors) were adjusted for, males had an OR of 2.26 for developing MSC (CI: 1.19-4.29, p = .012). CONCLUSIONS: Differences in the anatomical distribution of KCs by sex suggest different risk factors between sexes. There is a positive association between being male, smoking, rural dwelling, and a positive HIV status with KCs and being male and rural dwelling with MSC. The rural dwelling was a newly found association with skin cancer and warrants further investigation.
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Infecciones por VIH , Neoplasias Cutáneas , Estudios de Casos y Controles , Femenino , Infecciones por VIH/epidemiología , Humanos , Masculino , Melanoma , Factores de Riesgo , Neoplasias Cutáneas/epidemiología , Sudáfrica/epidemiología , Melanoma Cutáneo MalignoRESUMEN
A variety of well-characterized cutaneous paraneoplastic syndromes (PNS) are diagnosed during internal malignancies; however, the spectrum of keratinocyte skin neoplasms (KSC) related to PNS is still obscure. The aim of the present review is to compile and evaluate the literature data on PNS associated with a keratinocyte skin neoplasm (KSC). Employing Pubmed, MEDLINE was searched for KSC-associated PNS reports. Forty relevant entries were assembled, reporting a total of 41 PNS cases associated with a KSC (34 male). No review paper compiling this topic was found. Six distinct PNS entities were identified, and malignancy associated hypercalcemia (MAH; 78%), anemia (10%) and Bazex syndrome (5%) were the most frequently reported among them. 85% of the PNS were reported in association with SCC, 10% with BCC, and the rest with adnexal tumors. The median age of the patients at the time of PNS diagnosis was 58 years (range: five-83 years). In most cases the PNS was diagnosed either concurrently or after the KSC diagnosis. KSC predisposing conditions, as scars (22%) or hidradenitis suppurativa (20%), were reported in >70% of the PNS cases. Most PNS resolved after KSC treatment. In conclusion, PNS of a rather limited spectrum of entities are reported in association with KSC. They also seem to be rare, possibly reflecting a limited capacity of KSC to provoke overt PNS.
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In a 2013 study published in this Journal, Dacosta Byfield et al. used MediCare data to extract reliable estimations of the incidence (I = 6.16) and prevalence (P = 10.31) rates of advanced keratinocyte skin cancer (aKSC) per 100,000 US population. These data unmask a considerable disease burden of aKSC (tumor stages ≥ 3) compared to the corresponding projected SEER predictions in 2019 of all invasive cases (tumor stages ≥ 1). According to its incidence, aKSC ranks 19th out of 29 major SEER registered neoplasms and has an average disease duration of 1.67 years, which is the second shortest disease duration next only to pancreatic carcinoma. Furthermore, in support of the high disease aggressiveness of aKSC and using a calibration approach, we calculated a mortality estimate of 4.64 per 100,000 and a 5-year survival rate of 21.8% for this tumor, which corresponds to positions of 13th and 5th out of 29 cancers among the SEER tracked malignancies, respectively. Taken together, these data indicate a considerable disease burden and biologic aggressiveness of aKSC.
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Carcinoma Basocelular/epidemiología , Carcinoma de Células Escamosas/epidemiología , Costo de Enfermedad , Neoplasias Cutáneas/epidemiología , Carcinoma Basocelular/diagnóstico , Carcinoma Basocelular/patología , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patología , Humanos , Estadificación de Neoplasias , Prevalencia , Programa de VERF/estadística & datos numéricos , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patología , Tasa de Supervivencia , Factores de Tiempo , Estados Unidos/epidemiologíaRESUMEN
Relative keratinocyte skin cancer risks attributable to lifetime occupational and casual sunlight exposures of working school teachers are assessed across the state of Queensland for 1578 schools. Relative risk modeling utilizing annual ultraviolet exposure assessments of teachers working in different geographic locations and exposed during periods of measured daily playground duty times for each school were made for local administrative education districts by considering traditional school opening and closing hours, and playground lunchtime schedules. State-wide, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) relative risk estimates varied by 24% for BCC and 45% for SCC. The highest relative risk was calculated for the state's north (sunshine) coast education district which showed that risk could increase by as much as 32% for BCC and 64% for SCC due to differences in teacher duty schedules. These results highlight the importance of playground duty scheduling as a significant risk factor contributing to the overall burden of preventable keratinocyte skin cancers in Queensland.
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Carcinoma Basocelular/etiología , Carcinoma de Células Escamosas/etiología , Queratinocitos/metabolismo , Maestros/estadística & datos numéricos , Neoplasias Cutáneas/etiología , Factores de Edad , Australia , Geografía , Humanos , Exposición Profesional , Queensland , Factores de Riesgo , Estaciones del Año , Luz Solar , Factores de Tiempo , Rayos UltravioletaRESUMEN
Melanoma and keratinocyte skin cancer (KSC) are the most common types of cancer in White-skinned populations. Both tumor entities showed increasing incidence rates worldwide but stable or decreasing mortality rates. Rising incidence rates of cutaneous melanoma (CM) and KSC are largely attributed to increasing exposure to ultraviolet (UV) radiation, the main causal risk factor for skin cancer.Incidence rates of KSC, comprising of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), are much higher than that of melanoma. BCC development is mainly the cause of an intensive UV exposure in childhood and adolescence, while SCC development is related to chronic, cumulative UV exposure over decades. Although mortality is relatively low, KSC is an increasing problem for health care services causing significant morbidity.Cutaneous melanoma is rapidly increasing in White populations, with an estimated annual increase of around 3-7% over the past decades. In contrast to SCC, melanoma risk is associated with intermittent and chronic exposure to sunlight. The frequency of its occurrence is closely associated with the constitutive color of the skin and the geographical zone. Changes in outdoor activities and exposure to sunlight during the past 70 years are an important factor for the increasing incidence of melanoma. Mortality rates of melanoma show stabilization in the USA, Australia, and in European countries. In the USA even dropping numbers of death cases were recently reported, probably reflecting efficacy of the new systemic treatments.Among younger cohorts in some populations (e.g., Australia and New Zealand,), stabilizing or declining incidence rates of CM are observed, potentially caused by primary prevention campaigns aimed at reducing UV exposure. In contrast, incidence rates of CM are still rising in most European countries and in the USA. Ongoing trends towards thinner melanoma are largely ascribed to earlier detection.
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Neoplasias Cutáneas/epidemiología , Australia/epidemiología , Europa (Continente)/epidemiología , Humanos , Incidencia , Melanoma/epidemiología , Neoplasias Inducidas por Radiación/epidemiología , Nueva Zelanda/epidemiología , Estados Unidos/epidemiologíaRESUMEN
OBJECTIVES: To assess the cost-effectiveness of an educational intervention encouraging self-skin examinations for early detection of skin cancers among men older than 50 years. METHODS: A lifetime Markov model was constructed to combine data from the Skin Awareness Trial and other published sources. The model incorporated a health system perspective and the cost and health outcomes for melanoma, squamous and basal cell carcinomas, and benign skin lesions. Key model outcomes included Australian costs (2015), quality-adjusted life-years (QALYs), life-years, and counts of skin cancers. Univariate and probabilistic sensitivity analyses were undertaken to address parameter uncertainty. RESULTS: The mean cost of the intervention was A$5,298 compared with A$4,684 for usual care, whereas mean QALYs were 7.58 for the intervention group and 7.77 for the usual care group. The intervention was thus inferior to usual care. When only survival gain is considered, the model predicted the intervention would cost A$1,059 per life-year saved. The likelihood that the intervention was cost-effective up to A$50,000 per QALY gained was 43.9%. The model was stable to most data estimates; nevertheless, it relies on the specificity of clinical diagnosis of skin cancers and is subject to limited health utility data for people with skin lesions. CONCLUSIONS: Although the intervention improved skin checking behaviors and encouraged men to seek medical advice about suspicious lesions, the overall costs and effects from also detecting more squamous and basal cell carcinomas and benign lesions outweighed the positive health gains from detecting more thin melanomas.
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Concienciación , Carcinoma Basocelular/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Detección Precoz del Cáncer/economía , Conocimientos, Actitudes y Práctica en Salud , Melanoma/diagnóstico , Salud del Hombre/economía , Educación del Paciente como Asunto/economía , Autoexamen/economía , Neoplasias Cutáneas/diagnóstico , Factores de Edad , Anciano , Australia , Carcinoma Basocelular/economía , Carcinoma Basocelular/mortalidad , Carcinoma Basocelular/terapia , Carcinoma de Células Escamosas/economía , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/terapia , Ahorro de Costo , Análisis Costo-Beneficio , Técnicas de Apoyo para la Decisión , Detección Precoz del Cáncer/métodos , Costos de la Atención en Salud , Humanos , Masculino , Cadenas de Markov , Melanoma/economía , Melanoma/mortalidad , Melanoma/terapia , Persona de Mediana Edad , Modelos Económicos , Valor Predictivo de las Pruebas , Pronóstico , Años de Vida Ajustados por Calidad de Vida , Reproducibilidad de los Resultados , Factores de Riesgo , Factores Sexuales , Neoplasias Cutáneas/economía , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/terapia , Factores de Tiempo , Grabación en Video/economíaRESUMEN
BACKGROUND: The risk of skin malignancy among atopic dermatitis (AD) patients is not well established. OBJECTIVE: We reviewed the epidemiological evidence on the association between AD, naevi count, and the risk of cutaneous melanoma and keratinocyte skin cancer (KSC). METHODS: We included all studies that compared the naevi count and the risk of skin cancer (melanoma and/or KSC) between AD patients and unaffected individuals. We calculated summary relative risks (SRRs) and 95% confidence intervals (CI) through random effects models; explored correlates of between-studies heterogeneity using sub-group and sensitivity analysis; and assessed publication bias using a funnel-plot-based approach. RESULTS: The number of common naevi larger ≥2mm on the whole body was consistently lower among AD patients vs. unaffected individuals when measured by trained health professionals. The risk of melanoma was not increased among AD patients (SRR=0.77, 95%CI 0.44-1.35, I2=85%). We found a significantly increased risk of basal cell cancer (BCC) (SRR=1.34, 95%CI 1.03-1.75, I2=24.0%) but not for squamous cell cancer (SRR=1.91, 95% CI 0.74-4.91, I2=0.0%); however, only a few papers adjusted for phenotypic characteristics and/or sunlight exposure. We found no evidence of publication bias. CONCLUSIONS: AD patients may be at increased BCC risk; however, methodological limitations prevented from drawing definitive conclusions. Despite the lack of strong scientific evidence, AD patients should avoid excessive sun exposure, regularly perform skin self examination, and consult a doctor in case of a suspicious skin lesion.
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Carcinoma Basocelular/epidemiología , Dermatitis Atópica/epidemiología , Melanoma/epidemiología , Nevo/epidemiología , Neoplasias Cutáneas/epidemiología , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Queratinocitos/citología , Masculino , Persona de Mediana Edad , Fenotipo , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Melanoma survivors are at an increased risk of developing other malignancies, including keratinocyte skin cancer (KSC). While it is known that many risk factors for melanoma also impact risk of KSC in the general population, no previous study has investigated risk factors for KSC development in melanoma patients. OBJECTIVE: We assessed associations of personal and clinical characteristics, including skin phenotype and variations in the melanocortin 1 receptor (MC1R) gene, with KSC risk in melanoma patients. PATIENTS AND METHODS: We used prospective follow-up information on 1200 patients treated for melanoma at the Instituto Valenciano de Oncología, Spain, between 2000 and 2011. We computed hazard ratios and 95% confidence intervals (CIs) for the association of clinical, personal and genetic characteristics with risk of KSC, squamous cell carcinoma (SCC), or basal cell carcinoma (BCC) from Cox proportional hazard models. Five-year cumulative incidence based on competing risk models of SCC, BCC or KSC overall was computed using multivariate subdistribution hazard models. To assess predictive performance of the models, we computed areas under the receiver-operating characteristic curves (AUCs, discriminatory power) using cross-validation. RESULTS: Median follow-up was 57.2 months; a KSC was detected in 163 patients (13.6%). In multivariable Cox models, age, sex, sunburns, chronic sun exposure, past personal history of non-melanoma skin cancer or other non-cutaneous neoplasia, and the MC1R variants p.D294H and p.R163Q were significantly associated with KSC risk. A cumulative incidence model including age, sex, personal history of KSC, and of other non-cutaneous neoplasia had an AUC of 0.76 (95% CI: 0.71-0.80). When p.D294H and p.R163Q variants were added to the model, the AUC increased to 0.81 (95% CI: 0.77-0.84) (p-value for difference <0.0001). CONCLUSIONS: In addition to age, sex, skin characteristics, and sun exposure, p.R163Q and p.D294H MC1R variants significantly increased KSC risk among melanoma patients. Our findings may help identify patients who could benefit most from preventive measures.