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1.
Hum Mol Genet ; 2020 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-32716505

RESUMO

Cancers, including cutaneous melanoma, can cluster in families. In addition to environmental aetiological factors such as ultraviolet radiation, cutaneous melanoma has a strong genetic component. Genetic risks for cutaneous melanoma range from rare, high-penetrance mutations to common, low-penetrance variants. Known high-penetrance mutations account for only about half of all densely affected cutaneous melanoma families and the causes of familial clustering in the remainder is unknown. We hypothesise that some clustering is due to the cumulative effect of a large number of variants of individually small effect. Common, low-penetrance genetic risk variants can be combined into polygenic risk scores. We used a polygenic risk score for cutaneous melanoma to compare families without known high-penetrance mutations with unrelated melanoma cases and melanoma-free controls. Family members had significantly higher mean polygenic load for cutaneous melanoma than unrelated cases or melanoma-free healthy controls (Bonferroni corrected t-test P = 1.5 × 10-5 and 6.3 × 10-45, respectively). Whole genome sequencing of germline DNA from 51 members of 21 families with low polygenic risk for melanoma identified a CDKN2A p.G101W mutation in a single family but no other candidate new high-penetrance melanoma susceptibility genes. This work provides further evidence that melanoma, like many other common complex disorders, can arise from the joint action of multiple predisposing factors, including rare high-penetrance mutations, as well as via a combination of large numbers of alleles of small effect.

2.
BMC Public Health ; 20(1): 1028, 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32600382

RESUMO

BACKGROUND: Genomic risk information, based on common genomic susceptibility variants associated with risk of complex diseases such as cancer, may be incorporated into personalised prevention and screening strategies. We aimed to engage with members of the public, who are important stakeholders in this process, to further inform program development and other implementation outcomes such as acceptability and appropriateness. METHODS: Semi-structured interviews were undertaken with 30 participants (aged 24-69 years, 50% female) recruited from a pilot trial in which they received personalised genomic risk information for melanoma. We explored participants' views and attitudes towards offering general personal genomic risk information to the broader population. The data were analysed thematically. RESULTS: Two overarching themes relevant to implementation considerations were identified. Firstly, participants' preferences for accepting an offer of genomic risk information were based on family history, disease incidence and the possibility of prevention. Secondly, participants felt that the processes for offering risk information should be based on individual preferences, triaged according to risk and be supported by a health professional trained in genomics. CONCLUSIONS: Participants felt that offering personal genomic risk information to the general population to inform prevention and early detection recommendations is acceptable, particularly for common, complex conditions such as cancer. Understanding participants' preferences for receiving genomic risk information will assist with communication strategies and health workforce planning. We anticipate that these findings will contribute to the development of implementation strategies for incorporating genomic risk information into routine clinical practice.

3.
Trials ; 21(1): 594, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32605576

RESUMO

BACKGROUND: The Melanoma Genomics Managing Your Risk Study is a randomised controlled trial that aims to evaluate the efficacy of providing information on personal genomic risk of melanoma in reducing ultraviolet radiation (UV) exposure, stratified by traditional risk group (low or high phenotypic risk) in the general population. The primary outcome is objectively measured total daily Standard Erythemal Doses at 12 months. Secondary outcomes include UV exposure at specific time periods, self-reported sun protection and skin-examination behaviours, psychosocial outcomes, and ethical considerations surrounding offering genomic testing at a population level. A within-trial and modelled economic evaluation will be undertaken from an Australian health system perspective to assess the cost-effectiveness of the intervention. OBJECTIVE: To publish the pre-determined statistical analysis plan (SAP) before database lock and the start of analysis. METHODS: This SAP describes the data synthesis, analysis principles and statistical procedures for analysing the outcomes from this trial. The SAP was approved after closure of recruitment and before completion of patient follow-up. It outlines the planned primary analyses and a range of subgroup and sensitivity analyses. Health economic outcomes are not included in this plan but will be analysed separately. The SAP will be adhered to for the final data analysis of this trial to avoid potential analysis bias that may arise from knowledge of the outcome data. RESULTS: This SAP is consistent with best practice and should enable transparent reporting. CONCLUSION: This SAP has been developed for the Melanoma Genomics Managing Your Risk Study and will be followed to ensure high-quality standards of internal validity and to minimise analysis bias. TRIAL REGISTRATION: Prospectively registered with the Australian New Zealand Clinical Trials Registry, ID: ACTR N12617000691347 . Registered on 15 May 2017.

4.
Aust J Gen Pract ; 49(6): 355-362, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32464734

RESUMO

BACKGROUND AND OBJECTIVES: In Australia, the uptake of the sentinel lymph node biopsy (SLNB) appears low despite clinical practice guideline recommendations. The aim of this study was to describe the knowledge and attitudes of general practitioners (GPs) to SLNB. METHOD: GPs were recruited at an annual conference and a skin cancer skills workshop, and using GP professional communications. A mixed methods approach comprised a cross-sectional questionnaire and, for a subset of participants, semi-structured interviews. RESULTS: Overall, 231 GPs completed the questionnaire, of whom 23 were interviewed. One-third (32%) described themselves as quite or very familiar with the guidelines, and two-thirds (68%) thought that SLNB had an important role in the management of patients with melanoma. Of GPs who would discuss SLNB with eligible patients, <40% correctly identified that SLNB is recommended for patients with an invasive melanoma >1 mm thick. DISCUSSION: GPs were generally supportive of SLNB. Familiarity with the guidelines was low, particularly regarding which patients should be considered for SLNB.

5.
J Med Ethics ; 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32434901

RESUMO

Publics are key stakeholders in population genomic screening and their perspectives on ethical considerations are relevant to programme design and policy making. Using semi-structured interviews, we explored social views and attitudes towards possible future provision of personalised genomic risk information to populations to inform prevention and/or early detection of relevant conditions. Participants were members of the public (n=30) who had received information on their personal genomic risk of melanoma as part of a research project. The focus of the analysis presented here is participants' views regarding ethical considerations relevant to population genomic screening more generally. Data were analysed thematically and four key themes related to ethical considerations were identified: (i) personal responsibility for health: 'forewarned is forearmed'; (ii) perceptions of, and responses to, genetic fatalism; (iii) implications for parenting and reproduction; (iv) divided views on choosing to receive genomic risk information. Ethical considerations underlying these themes include the valorisation of information and choice, paternalism, non-directiveness and increasing responsibilisation of individuals in health and healthcare. These findings arguably indicate a thin public conceptualisation of population genomic testing, which draws heavily on how these themes tend to be described in existing social discourses. Findings suggest that further public engagement is required to increase complexity of debate, to consider (for example) the appropriate place of individual and social interests in population genomic testing. Further discernment of relevant ethical approaches, drawing on ethical frameworks from both public health and clinical settings, will also assist in determining the appropriate implementation of population genomic screening for complex conditions.

6.
BJGP Open ; 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32295791

RESUMO

BACKGROUND: In Australia, melanoma is managed in primary and secondary care settings. An individual concerned about a suspicious lesion typically presents first to their GP. AIM: To identify factors influencing GPs' decisions to diagnose, treat, or refer patients with suspected melanoma. DESIGN & SETTING: Semi-structured interviews were undertaken with 23 GPs working in general practice or skin cancer clinics in Australia. METHOD: The semi-structured interviews were audio-recorded, de-identified, and professionally transcribed. Thematic analysis was used to analyse the data. RESULTS: Considerable variation existed in GPs' self-reported confidence and involvement in melanoma management. Multiple factors were identified as influencing GPs' decisions to diagnose, treat, or refer patients with suspected or confirmed melanoma. Health system level factors included the overlapping roles of GPs and specialists, and access to and/or availability of specialists. Practice level factors included opportunities for formal and informal training, and having a GP with a special interest in skin cancer within their practice. GP and patient level factors included the GP's clinical interests, the clinical features (for example, site and size) and histopathology of the suspected melanoma, eligibility for possible sentinel lymph node biopsy, and patient preferences. For some GPs, concerns over misdiagnosis and the option of referring patients at any stage in the melanoma management continuum appeared to affect their interest and confidence in melanoma management. CONCLUSION: GP involvement in melanoma patient care can extend well beyond cancer screening, prevention and supportive care roles to include provision of definitive melanoma patient management. GPs with an interest in being involved in melanoma management should be encouraged and supported to develop the skills needed to manage these patients, and to refer when appropriate.

7.
BMJ Open ; 10(2): e032636, 2020 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-32111612

RESUMO

INTRODUCTION: Sentinel lymph node biopsy (SLNB) is a diagnostic procedure developed in the 1990s. It is currently used to stage patients with primary cutaneous melanoma, provide prognostic information and guide management. The Australian Clinical Practice Guidelines state that SLNB should be considered for patients with cutaneous melanoma >1 mm in thickness (or >0.8 mm with high-risk pathology features). Until recently, sentinel lymph node (SLN) status was used to identify patients who might benefit from a completion lymph node dissection, a procedure that is no longer routinely recommended. SLN status is now also being used to identify patients who might benefit from systemic adjuvant therapies such as anti-programmed cell death 1 (PD1) checkpoint inhibitor immunotherapy or BRAF-directed molecular targeted therapy, treatments that have significantly improved relapse-free survival for patients with resected stage III melanoma and improved overall survival of patients with unresectable stage III and stage IV melanoma. Australian and international data indicate that approximately half of eligible patients receive an SLNB. METHODS AND ANALYSIS: This mixed-methods study seeks to understand the structural, contextual and cultural factors affecting implementation of the SLNB guidelines. Data collection will include: (1) cross-sectional questionnaires and semistructured interviews with general practitioners and dermatologists; (2) semistructured interviews with other healthcare professionals involved in the diagnosis and early definitive care of melanoma patients and key stakeholders including researchers, representatives of professional colleges, training organisations and consumer melanoma groups; and (3) documentary analysis of documents from government, health services and non-government organisations. Descriptive analyses and multivariable regression models will be used to examine factors related to SLNB practices and attitudes. Qualitative data will be analysed using thematic analysis. ETHICS AND DISSEMINATION: Ethics approval has been granted by the University of Sydney. Results will be disseminated through publications and presentations to clinicians, patients, policymakers and researchers and will inform the development of strategies for implementing SLNB guidelines in Australia.

8.
Aust N Z J Public Health ; 44(2): 111-115, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32190955

RESUMO

INTRODUCTION: A Melanoma Screening Summit was held in Brisbane, Australia, to review evidence regarding current approaches for early detection of melanomas and explore new opportunities. RESULTS: Formal population-based melanoma screening is not carried out in Australia, but there is evidence of considerable opportunistic screening as well as early detection. Biopsy rates are rising and most melanomas are now diagnosed when in situ. Based on evidence review and expert opinion, the Summit attendees concluded that there is currently insufficient information in terms of comparative benefits, harms and costs to support change from opportunistic to systematic screening. Assessment of gains in precision and cost-effectiveness of integrating total body imaging, artificial intelligence algorithms and genetic risk information is required, as well as better understanding of clinical and molecular features of thin fatal melanomas. CONCLUSIONS: Research is needed to understand how to further optimise early detection of melanoma in Australia. Integrating risk-based population stratification and more precise diagnostic tests is likely to improve the balance of benefits and harms of opportunistic screening, pending assessment of cost-effectiveness. Implications for public health: The Summit Group identified that the personal and financial costs to the community of detecting and treating melanoma are rising, and this may be mitigated by developing and implementing a more systematic process for diagnosing melanoma.


Assuntos
Detecção Precoce de Câncer , Programas de Rastreamento/métodos , Melanoma/diagnóstico , Neoplasias Cutâneas/diagnóstico , Austrália , Consenso , Detecção Precoce de Câncer/métodos , Política de Saúde , Humanos , Melanoma/prevenção & controle , Prática de Saúde Pública , Neoplasias Cutâneas/prevenção & controle
9.
Int J Cancer ; 147(5): 1391-1396, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32067220

RESUMO

There is little long-term follow-up information about how the number of melanoma deaths and case fatality vary over time according to the measured thickness of melanoma at diagnosis. This population-based longitudinal cohort study examines patterns and trends in case fatality among 44,531 people in Queensland (Australia) diagnosed with a single invasive melanoma (International Classification of Diseases for Oncology, third revision [ICD-O-3], C44, Morphology 872-879) between 1987 and 2011, including 11,883 diagnosed between 1987 and 1996, with up to 20 years follow-up (to December 2016). The 20-year case fatality increased by thickness, with the percentage of melanoma deaths within 20 years of diagnosis being up to 4.8% for melanomas with measured thickness <0.80 mm, 10.6% for tumors 0.8 to <1.0 mm and generally more than 30% for melanomas measuring 3 mm and more. For melanomas <1.0 mm, most deaths occurred between 5 and 20 years after diagnosis, whereas for thicker melanomas the reverse was true with most deaths occurring within the first 5 years. Five-year case fatality decreased over successive calendar time periods for melanomas <1.0 mm, but not for melanomas ≥1.0 mm. These findings demonstrate that the time course for fatal melanomas varies markedly according to tumor thickness at diagnosis. Improved understanding of the patient factors and characteristics of melanomas, in addition to tumor thickness, which increase the likelihood of progression, is needed to guide clinical diagnosis, communication with patients and ongoing surveillance pathways of patients with potentially fatal lesions.

11.
Public Health Res Pract ; 29(2)2019 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-31384883

RESUMO

While Australia now has well-established national screening programs for breast, bowel and cervical cancers, research continues into the feasibility of developing systematic screening programs for a number of other cancers. In this paper, experts in their fields provide perspectives on the current state of play and future directions for screening and surveillance for melanoma, Lynch syndrome, and liver, lung and prostate cancers in Australia. Although the evidence does not support population screening, there may be opportunities to prevent thousands of deaths through systematic approaches to the early detection of lung cancer and melanoma, testing for Lynch syndrome, and organised surveillance for hepatocellular carcinoma among individuals at high risk - guided by targeted research. The paper also looks at what impact new prostate specific antigen testing guidelines are having on screening for prostate cancer.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Detecção Precoce de Câncer/estatística & dados numéricos , Neoplasias Hepáticas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Programas de Rastreamento/estatística & dados numéricos , Melanoma/diagnóstico , Neoplasias da Próstata/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália , Detecção Precoce de Câncer/tendências , Previsões , Humanos , Masculino , Programas de Rastreamento/tendências , Pessoa de Meia-Idade
12.
Appl Health Econ Health Policy ; 17(5): 669-681, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31228015

RESUMO

OBJECTIVE: This study aimed to evaluate the cost effectiveness of a newly developed psycho-educational intervention to reduce fear of cancer recurrence (FCR) in early-stage melanoma patients. METHODS: A within-trial cost-effectiveness and cost-utility analysis was conducted from the Australian health system perspective using data from linked Medicare records. Outcomes included FCR, measured with the severity subscale of the FCR Inventory; quality-adjusted life years (QALYs) measured using the preference-based instrument, Assessment of Quality of Life-8 Dimensions (AQoL-8D) and 12-month survival. An incremental cost-effectiveness ratio (ICER) was calculated for two economic outcomes: (1) cost per additional case of 'high' FCR avoided and (2) cost per QALY gained. Means and 95% CIs around the ICER were generated from non-parametric bootstrapping with 1000 replications. RESULTS: A total of 151 trial participants were included in the economic evaluation. The mean cost of the psycho-educational intervention was AU$1614 per participant, including intervention development costs. The ICER per case of high FCR avoided was AU$12,903. The cost-effectiveness acceptability curve demonstrated a 78% probability of the intervention being cost effective relative to the control at a threshold of AU$50,000 per extra person avoiding FCR. The ICER per QALY gained was AU$116,126 and the probability of the intervention being cost effective for this outcome was 36% at a willingness to pay of AU$50,000 per QALY. CONCLUSION: The psycho-educational intervention reduced FCR at 12 months for people at high risk of developing another melanoma and may represent good value for money. For the QALY outcome, the psycho-educational intervention is unlikely to be cost effective at standard government willingness-to-pay levels. The trial was prospectively registered in the Australian and New Zealand Clinical Trials Registry (CTRN12613000304730).

13.
BJGP Open ; 3(1): bjgpopen18X101633, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31049413

RESUMO

Background: As part of a pilot randomised controlled trial examining the impact of personal melanoma genomic risk information on behavioural and psychosocial outcomes, GPs were sent a booklet containing their patient's genomic risk of melanoma. Aim: Using this booklet as an example of genomic risk information that might be offered on a population-level in the future, this study explored GP attitudes towards communicating genomic risk information and resources needed to support this process. Design & setting: Semi-structured interviews were conducted with 22 Australian GPs. Method: The interviews were recorded and transcribed, and data were analysed thematically. Results: GPs in this sample believed that communicating genomic risk may become a responsibility within primary care and they recommended a shared decisionmaking approach to guide the testing process. Factors were identified that may influence how and when GPs communicate genomic risk information. GPs view genomics-based risk as one of many disease risk factors and feel that this type of information could be applied in practice in the context of overall risk assessment for diseases for which prevention and early detection strategies are available. They believe it is important to ensure that patients understand their genomic risk and do not experience long-term adverse psychological responses. GPs desire clinical practice guidelines that specify recommendations for genomic risk assessment and patient management, point-of-care resources, and risk prediction tools that include genomic and traditional risk factors. Conclusion: These findings will inform the development of resources for preparing GPs to manage and implement genomic risk information in practice.

14.
Cancer Epidemiol ; 61: 8-13, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31102918

RESUMO

BACKGROUND: Exposure to ultraviolet radiation from sunlight is directly associated with melanoma skin cancer, however reducing sun-exposure can be difficult to achieve at a population level. METHODS: Using a genomic risk information behaviour change trial for melanoma prevention, we classified participants as risk-seeking, risk-neutral or risk-averse for domain-specific risk taking (DOSPERT). One-way ANOVA determined the association between socio-demographic characteristics and risk-taking score, and multivariable linear regression ascertained impact of an individual's underlying risk propensity on an objective measure of sun-exposure, standard erythemal dose (SED), at 3-months follow-up. RESULTS: Of 119 participants, mean age 53 years; 50% males, 87% had a personal/family history of cancer; 19% were classified risk-seeking, 57% risk-neutral. The mean risk-taking score was significantly higher in younger participants (≤50 years: 13.86 vs. >50 years: 11.11, p = 0.003); and lower in those with a personal/family history of skin cancer versus without (10.55 vs 13.33, p = 0.009). Risk averse individuals had lower weekly mean SEDs at 3-months than risk neutral and risk seeking individuals (2.56, 5.81, 4.81 respectively, p = 0.01). Risk seekers showed fewer sun protective habits (p < 0.001); and higher intentional tanning, (p = 0.01). At 3-months, risk seekers attained 16%-54% lower SEDs in the genomic information group compared with controls, however this was not significantly different across risk groups (interaction p = 0.13). CONCLUSION: An individual's underlying risk attitude is likely associated with sun-exposure behaviours, and may modify the effect of a genomic risk information behaviour change intervention. Young people and risk seekers may benefit most from being given information on their genetic risk of melanoma.


Assuntos
Genômica/métodos , Comportamentos Relacionados com a Saúde/fisiologia , Melanoma/prevenção & controle , Neoplasias Cutâneas/prevenção & controle , Banho de Sol/psicologia , Luz Solar/efeitos adversos , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Assunção de Riscos
15.
Ann Epidemiol ; 35: 1-3, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31036443

RESUMO

The under-representation of women in leadership in scientific fields presents a serious problem. Gender diversity is integral to innovation and productivity, and inequality leads to loss of gender talent in science including epidemiology. This policy brief summarizes some of the key dimensions and determinants contributing to gender-equity gaps in epidemiology and other scientific fields, relevant to developed countries where there is more published evidence. Women in scientific fields hold fewer positions on editorial boards, lack equal representation in speaking engagements at conferences, and are less likely to publish or receive top tier grant funding. Reasons for these inequities range from unconscious bias, biased promotion systems, and traditional norms in the division of family life and labor in our society leading to the attrition of women in academia. Addressing the problem of gender inequity, as a component of gender inequality, will provide an ethical basis to advance innovation. Data on gender equity in the field of epidemiology are sparse. We call on academic institutions, professional societies and associations, and editorial boards relevant to epidemiology (as well as other academic disciplines more broadly) to take meaningful action to build an evidence base as to the extent of gender inequities in epidemiologic research, teaching, policy, and practice. We outline some of the necessary steps required to achieve gender equity, such as career development and mentoring programs, institutional support, and programs to address bias.


Assuntos
Mobilidade Ocupacional , Liderança , Epidemiologia , Feminino , Humanos , Mentores , Salários e Benefícios , Sexismo
16.
JAMA Dermatol ; 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31090868

RESUMO

Importance: Skin self-examination (SSE) is a key factor in the early detection of melanoma, and many new and recurrent melanomas are first detected by patients themselves or their family members. Objective: To explore the views of patients with melanoma regarding SSE in general, as well as their attitudes toward using novel digital technologies to support their own SSE. Design, Setting, and Participants: Qualitative study with semistructured interviews that were conducted from June 20 to December 12, 2016, with 37 individuals in Sydney, Australia, who were previously treated for a first primary localized melanoma during 2014 and had not had a recurrence or new primary melanoma in the time since treatment. Main Outcomes and Measures: Patients' views and experiences, analyzed thematically. Results: A total of 37 patients (11 women and 26 men; median age, 67 years [interquartile range, 59.5-72 years]) were interviewed. Participants perceived SSE as important for the early identification of local recurrence or new primary melanomas. Despite this belief, participants did not report undertaking full-body SSE on a regular basis. Factors that influenced their low engagement in thorough SSE included lack of self-efficacy, reliance on clinician consultations as the primary means of melanoma detection, and fear of cancer recurrence. Regarding the use of digital technology to assist with SSE, the key motivating factors in favor of such tools were the ability to track changes in lesions over time and the use of automated reminders to undertake SSE. Deterrents included a lack of confidence in undertaking SSE and in using new technology. Conclusions and Relevance: Patients with melanoma are aware of the importance of thorough skin examinations. However, a lack of confidence in their ability to undertake SSE and reliance on clinicians as the primary means of melanoma detection may inhibit patients from undertaking regular and thorough SSE. Patients may benefit from new digital technologies that assist them in undertaking SSE, provided they have appropriate education and technical support.

17.
Lancet Child Adolesc Health ; 3(5): 332-342, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30872112

RESUMO

BACKGROUND: Germline variants in the melanocortin 1 receptor gene (MC1R) might increase the risk of childhood and adolescent melanoma, but a clear conclusion is challenging because of the low number of studies and cases. We assessed the association of MC1R variants with childhood and adolescent melanoma in a large study comparing the prevalence of MC1R variants in child or adolescent patients with melanoma to that in adult patients with melanoma and in healthy adult controls. METHODS: In this retrospective pooled analysis, we used the M-SKIP Project, the Italian Melanoma Intergroup, and other European groups (with participants from Australia, Canada, France, Greece, Italy, the Netherlands, Serbia, Spain, Sweden, Turkey, and the USA) to assemble an international multicentre cohort. We gathered phenotypic and genetic data from children or adolescents diagnosed with sporadic single-primary cutaneous melanoma at age 20 years or younger, adult patients with sporadic single-primary cutaneous melanoma diagnosed at age 35 years or older, and healthy adult individuals as controls. We calculated odds ratios (ORs) for childhood and adolescent melanoma associated with MC1R variants by multivariable logistic regression. Subgroup analysis was done for children aged 18 or younger and 14 years or younger. FINDINGS: We analysed data from 233 young patients, 932 adult patients, and 932 healthy adult controls. Children and adolescents had higher odds of carrying MC1R r variants than did adult patients (OR 1·54, 95% CI 1·02-2·33), including when analysis was restricted to patients aged 18 years or younger (1·80, 1·06-3·07). All investigated variants, except Arg160Trp, tended, to varying degrees, to have higher frequencies in young patients than in adult patients, with significantly higher frequencies found for Val60Leu (OR 1·60, 95% CI 1·05-2·44; p=0·04) and Asp294His (2·15, 1·05-4·40; p=0·04). Compared with those of healthy controls, young patients with melanoma had significantly higher frequencies of any MC1R variants. INTERPRETATION: Our pooled analysis of MC1R genetic data of young patients with melanoma showed that MC1R r variants were more prevalent in childhood and adolescent melanoma than in adult melanoma, especially in patients aged 18 years or younger. Our findings support the role of MC1R in childhood and adolescent melanoma susceptibility, with a potential clinical relevance for developing early melanoma detection and preventive strategies. FUNDING: SPD-Pilot/Project-Award-2015; AIRC-MFAG-11831.


Assuntos
Biomarcadores Tumorais/genética , Mutação em Linhagem Germinativa , Melanoma/genética , Receptor Tipo 1 de Melanocortina/genética , Neoplasias Cutâneas/genética , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Criança , Feminino , Predisposição Genética para Doença , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo Genético , Estudos Retrospectivos
18.
J Am Acad Dermatol ; 81(2): 386-394, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30731170

RESUMO

BACKGROUND: Although rare in the general population, highly penetrant germline mutations in CDKN2A are responsible for 5%-40% of melanoma cases reported in melanoma-prone families. We sought to determine whether MELPREDICT was generalizable to a global series of families with melanoma and whether performance improvements can be achieved. METHODS: In total, 2116 familial melanoma cases were ascertained by the international GenoMEL Consortium. We recapitulated the MELPREDICT model within our data (GenoMELPREDICT) to assess performance improvements by adding phenotypic risk factors and history of pancreatic cancer. We report areas under the curve (AUC) with 95% confidence intervals (CIs) along with net reclassification indices (NRIs) as performance metrics. RESULTS: MELPREDICT performed well (AUC 0.752, 95% CI 0.730-0.775), and GenoMELPREDICT performance was similar (AUC 0.748, 95% CI 0.726-0.771). Adding a reported history of pancreatic cancer yielded discriminatory improvement (P < .0001) in GenoMELPREDICT (AUC 0.772, 95% CI 0.750-0.793, NRI 0.40). Including phenotypic risk factors did not improve performance. CONCLUSION: The MELPREDICT model functioned well in a global data set of familial melanoma cases. Adding pancreatic cancer history improved model prediction. GenoMELPREDICT is a simple tool for predicting CDKN2A mutational status among melanoma patients from melanoma-prone families and can aid in directing these patients to receive genetic testing or cancer risk counseling.


Assuntos
Inibidor p16 de Quinase Dependente de Ciclina/genética , Predisposição Genética para Doença , Modelos Logísticos , Melanoma/genética , Neoplasias Pancreáticas , Neoplasias Cutâneas/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Criança , Testes Genéticos , Mutação em Linhagem Germinativa , Heterozigoto , Humanos , Internacionalidade , Pessoa de Meia-Idade , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/genética , Fenótipo , Valor Preditivo dos Testes , Probabilidade , Curva ROC , Fatores de Risco , Adulto Jovem
19.
Australas J Dermatol ; 60(2): 118-125, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30302753

RESUMO

BACKGROUND/OBJECTIVES: There are limited population-based data documenting the incidence and management of lentigo maligna (LM) and invasive lentigo maligna melanoma (LMM). We report the data on occurrence and management of LM and LMM in an Australian population. METHODS: Prospective collection of incidence and clinician-reported management of melanoma in situ (MIS; n = 450, capped) and localised invasive melanoma (n = 3251) notified to the New South Wales Cancer Registry over 12-months in 2006-2007. RESULTS: The estimated annual incidence of all MIS was 27.0 per 100 000 (LM 12.2, non-LM MIS 5.9 and unclassified MIS 9.0). Patients with LM or LMM were on average approximately 10 years older than those with other melanoma subtypes (P < 0.001). The head and neck was the location of 59% of LM, 44% of LMM and <20% of other melanoma subtypes (P < 0.001). The majority of LM and LMM were treated only by specialists. Diagnostic partial biopsies were more frequent for LM and LMM than for other melanoma subtypes, and primary care physicians were more likely than specialists to do a punch partial biopsy than a shave biopsy. The reported median definitive excision margin for LM was 5.0 mm compared with 7.2 mm for non-LM MIS (P = 0.001). CONCLUSIONS: In this Australian population, LM was twice as frequent as other types of MIS. Improved strategies for diagnosis and management are required.


Assuntos
Sarda Melanótica de Hutchinson/epidemiologia , Melanoma/epidemiologia , Neoplasias Cutâneas/epidemiologia , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Austrália/epidemiologia , Biópsia , Feminino , Neoplasias de Cabeça e Pescoço/epidemiologia , Humanos , Sarda Melanótica de Hutchinson/cirurgia , Incidência , Masculino , Margens de Excisão , Melanoma/cirurgia , Pessoa de Meia-Idade , Estudos Prospectivos , Encaminhamento e Consulta/estatística & dados numéricos , Distribuição por Sexo , Neoplasias Cutâneas/cirurgia
20.
Fam Pract ; 36(2): 237-246, 2019 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-29800131

RESUMO

BACKGROUND: Personalized risk assessments using prediction models that incorporate several melanoma risk factors may promote melanoma-prevention behaviours. OBJECTIVES: To evaluate the effect on short-term melanoma-prevention behaviours of web-based, real-time, model-generated personalized melanoma risk information and tailored prevention advice, and its feasibility and clinician acceptability. METHODS: Between February and April 2016, in an open randomized controlled trial across four general medical practices in New South Wales, Australia, 272 patients were randomly allocated to receive (i) real-time model-generated personalized melanoma risk assessment and tailored melanoma-prevention advice or (ii) generic melanoma-prevention advice. We measured self-reported melanoma-prevention behaviours at baseline and 6 weeks and the intervention's feasibility and acceptability. RESULTS: Follow-up questionnaires were completed by 185 patients at 6 weeks: 174 assessed as average risk and 11 as high or very high risk. There were no statistically significant differences between intervention and control patients in sun protection, sun exposure or early diagnosis behaviours. When stratified by melanoma risk, average risk patients in the intervention group appeared to show greater sun protection at 6 weeks (mean difference = 0.23, on a scale of 1-5; 95% confidence interval: 0.01 to 0.45; P = 0.04) than patients in the control group; the P value for interaction between intervention and risk category was 0.10. There was favourable feedback from patients and general practitioners. CONCLUSIONS: Web-based delivery in general practice of real-time, model-generated personalized melanoma risk prediction and tailored melanoma-prevention advice is feasible and acceptable. An apparent increase in sun protection behaviour in average risk patients warrants further evaluation in different risk groups.


Assuntos
Medicina Geral , Melanoma/prevenção & controle , Medição de Risco/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , New South Wales , Roupa de Proteção , Medição de Risco/métodos , Comportamento de Redução do Risco , Protetores Solares , Inquéritos e Questionários
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