Skin Cancer Genetics PDF

GENETICS OF SKIN Dr Temba Mudariki CANCER LEARNING OUTCOMES Understanding the Genetics of Skin Cancer Clinical Management of Hereditary Skin Cancers Genetics of Basal Cell Carcinoma, Squamous Cell Carcinoma, and Melanoma Risk-reducing Strategies for Hereditary S...

GENETICS OF SKIN Dr Temba Mudariki CANCER LEARNING OUTCOMES Understanding the Genetics of Skin Cancer Clinical Management of Hereditary Skin Cancers Genetics of Basal Cell Carcinoma, Squamous Cell Carcinoma, and Melanoma Risk-reducing Strategies for Hereditary Skin Cancers Psychosocial Factors and Genetic Testing Ethical and Legal Considerations Sample Footer Text 1/30/2024 2  PREVALENCE OF SKIN CANCER Skin cancer encompasses a broad spectrum of malignancies Over 100 distinct types of tumours clinically identifiable on the skin Range from the more common basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) to the less frequent but highly aggressive melanoma Many of these skin cancers exhibit familial and/or inherited components Molecular Medicine 1/30/2024 3  SKIN CANCER STATISTICS Skin cancer, inclusive of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma  Most prevalent types of cancer globally, and the United Kingdom  In the UK, skin cancer represents a significant public health issue due to its high incidence and associated health care burden. Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most frequently diagnosed Melanoma- less common, poses a considerable threat due to its potential to metastasise Melanoma has been increasing in the UK over the years The UK had one of the highest rates of skin cancer in Europe  over 100,000 new cases reported each year  Approximately 75,000 were non-melanoma skin cancers (predominantly BCC and SCC), and approximately 16,000 cases were melanoma. Sample Footer Text 1/30/2024 4 IMPORTANCE OF GENETIC FACTORS Environmental factors -sun exposure are well- recognized contributors to skin cancer Essential to underscore the significance of genetic factors  shaping an individual's susceptibility to these malignancies. Genetic predisposition significantly influences an individual's susceptibility to various types of skin cancer. Sample Footer Text 1/30/2024 5 GENETIC PREDISPOSITION Preventive Strategies  Personalized sun protection measures, lifestyle modifications, and tailored screening protocols Early Detection  Improving treatment outcomes and reducing the morbidity associated with advanced stages of the disease Tailored Treatment Approaches  Targeted therapies or immunotherapies, which may be particularly effective for individuals with specific genetic mutations. Impact of Family History and Hereditary Syndromes  Hereditary components can inform risk assessment and guide the implementation of preventive measures and early detection strategies for at-risk individuals  Xeroderma pigmentosum (XP), basal cell nevus syndrome (BCNS) etc. Sample Footer Text 1/30/2024 6  UNDERSTANDING THE GENETIC BASIS OF BASAL CELL CARCINOMA, SQUAMOUS CELL CARCINOMA, AND MELANOMA Genetics of Basal Cell Carcinoma (BCC) Most prevalent form of skin cancer Genetic predisposition plays a crucial role in shaping an individual's susceptibility to BCC Inherited pathogenic variants in specific genes  PTCH1 and PTCH2, are associated with an elevated risk  linked to a hereditary condition known as basal cell nevus syndrome (BCNS). Pathogenic variants in the PTCH1 gene  Key regulator of the hedgehog signalling pathway  Sporadic cutaneous BCCs 1/30/2024 7  UNDERSTANDING THE GENETIC BASIS OF BASAL CELL CARCINOMA, SQUAMOUS CELL CARCINOMA, AND MELANOMA Basal Cell Nevus Syndrome (BCNS)  Basal cell nevus syndrome - also known as Gorlin syndrome  autosomal dominant condition characterized by the presence of multiple basal cell carcinomas  Along with other developmental abnormalities  BCNS is often caused by germline mutations in the PTCH1 gene  Genetic predisposition and the development of BCC in affected individuals Genetic Syndromes and DNA Repair Pathways 1/30/2024 8 GENETIC SYNDROMES AND DNA REPAIR PATHWAYS Genetic predisposition to SCC is closely linked to syndromes such as oculocutaneous albinism Affects pigmentation and is associated with an increased susceptibility to developing skin cancer Epidermolysis bullosa, a group of inherited connective tissue diseases  Characterized by blistering of the skin and mucous membranes  Associated with an elevated risk of SCC due to chronic skin damage and inflammation Fanconi anaemia, a rare genetic disorder affecting DNA repair, is also linked to an increased predisposition to SCC. 1/30/2024 9 GENETIC SYNDROMES AND DNA REPAIR PATHWAYS Genetics of Squamous Cell Carcinoma (SCC)  Common form of skin cancer, is also influenced by genetic factors  Syndromes such as oculocutaneous albinism, epidermolysis bullosa, and Fanconi anaemia are associated with an increased risk of SCC, highlighting the genetic predisposition to this malignancy. Genes Associated with SCC DNA repair pathways 1/30/2024 10 GENETICS OF MELANOMA Melanoma- a less common but highly aggressive type of skin cancer Has a strong genetic component. A subset of melanomas arises in multiple-case families and can be inherited in an autosomal dominant fashion. Genes Associated with Melanoma CDKN2A is a major germline tumour suppressor gene associated with increased melanoma risk Pathogenic variants in CDKN2A may account for a significant percentage of familial melanomas Germline pathogenic variants in other genes such as CDK4, MITF, and BAP1 are also associated with an increased risk of melanoma 1/30/2024 11  GENETICS OF MELANOMA Hereditary Syndromes Associated with Skin Cancer  Several hereditary syndromes -basal cell nevus syndrome (BCNS), xeroderma pigmentosum (XP), Rombo syndrome, and Bazex-Dupré-Christol syndrome Role of Genetic Variations  Genome-wide association studies show promise for identifying  Low-penetrance susceptibility alleles for many complex diseases, including melanoma 1/30/2024 12 SURVEILLANCE AND SCREENING Surveillance and screening play a pivotal role in the clinical management of hereditary skin cancers. Regular skin examinations, dermoscopy, and total body photography are essential for early detection of skin lesions and prompt intervention, thereby improving patient outcomes. 1/30/2024 13 GENETIC COUNSELLING AND TESTING Genetic counselling and testing are integral components of the clinical management of hereditary skin cancers. They enable individuals with a family history of skin cancer to understand their genetic risk, make informed decisions about preventive measures, and access personalized screening and management strategies. 1/30/2024 14 SURGICAL INTERVENTIONS Surgical interventions, including Mohs micrographic surgery, excisional surgery, and lymph node dissection, are key components of the clinical management of hereditary skin cancers, particularly melanoma. These interventions aim to achieve complete tumour removal and minimize the risk of recurrence. 1/30/2024 15 IMMUNOTHERAPY AND TARGETED THERAPY Immunotherapy and targeted therapy have revolutionized the treatment landscape for advanced melanoma. These approaches, including immune checkpoint inhibitors and targeted agents, have significantly improved outcomes for patients with metastatic melanoma and are an essential component of clinical management. Risk-reducing Strategies for Hereditary Skin Cancers  Play a crucial role in mitigating the risk of skin cancer in individuals with genetic predisposition. Sample Footer Text 1/30/2024 16  SUN PROTECTION AND LIFESTYLE MODIFICATIONS Implementing sun protection measures including - sun avoidance, sunscreen use, protective clothing, and seeking shade is paramount for reducing the risk of skin cancer in at-risk individuals. Lifestyle modifications also encompass smoking cessation and a healthy diet, contributing to overall risk reduction. Sample Footer Text 1/30/2024 17 CHEMOPREVENTIVE AGENTS Chemopreventive agents, such as oral retinoids and nonsteroidal anti-inflammatory drugs (NSAIDs), have been investigated for their potential role in reducing the risk of skin cancer, particularly in high-risk populations.  These agents hold promise in complementing other risk-reducing strategies. Effectiveness of Risk-reducing Strategies Evidence supports the effectiveness of risk-reducing strategies in decreasing the incidence of skin cancer and improving patient outcomes Clinical and risk-reducing aspects, healthcare providers can offer comprehensive care, contributing to improved outcomes and a reduction in the overall burden of hereditary skin cancers. Sample Footer Text 1/30/2024 18 RISK, EMOTIONAL IMPACT AND FAMILY DYNAMICS Perceived Risk - Individuals' perceptions of their own risk of developing cancer based on family history  Other factors can heavily influence their willingness to undergo genetic testing Emotional Impact  Emotional impact of genetic testing for inherited cancer risk can be profound Familial Dynamics  Family dynamics, including communication patterns, support systems, and cultural beliefs Sample Footer Text 1/30/2024 19 PSYCHOSOCIAL SUPPORT AND COUNSELLING Psychosocial factors, including perceived risk, emotional impact, and familial dynamics, significantly influence individuals' decisions regarding genetic testing for inherited cancer risk. Understanding these factors is crucial for providing tailored support and guidance to individuals considering genetic testing. Risk-reducing Behaviours in Individuals with a Family History of Melanoma  The emotional impact of genetic testing  Encompassing anxiety, uncertainty, and fear of stigmatization.  Psychosocial support and counselling play a pivotal role in addressing these emotional challenges and facilitating informed decision-making. Early-detection Behaviours  Promptly reporting concerning skin lesions, adhering to surveillance recommendations, and being aware of melanoma warning signs Sample Footer Text 1/30/2024 20 INTERVENTION STUDIES ADDRESSING PSYCHOSOCIAL AND BEHAVIOURAL ISSUES: Intervention studies have been pivotal in addressing psychosocial and behavioural issues in high-risk families.  Studies encompass psychosocial support interventions, educational programs, and counselling services aimed at enhancing coping strategies and promoting informed decision-making. Psychosocial Support Interventions  Support groups, individual counselling, and online resources Educational Programs and Counselling Services  Communication strategies, and decision-making support to individuals considering genetic testing for inherited cancer risk Impact of Intervention Studies  Improving psychosocial well-being, enhancing risk-reducing behaviours, and promoting informed decision-making among individuals and families at high risk of hereditary skin cancers. Sample Footer Text 1/30/2024 21