EPIDEMIOLOGY AND GENETICS OF EARLY ONSET BASAL CELL CARCINOMA

早发性基底细胞癌的流行病学和遗传学

• 批准号: 7147297
• 负责人: SUSAN T MAYNE
• 金额: $ 22.05万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7147297
• 关键词: aging; basal cell carcinoma; clinical research; epidemiology; gene mutation; genes; genetics; neoplasm /cancer; smoking

Basal cell carcinoma (BCC) is the most common malignancy in the United States; however, it has been relatively understudied in epidemiologic research. Temporal trends indicate that BCC incidence is increasing overall, in young adults, and especially in young women. Data from "early onset" cases support the concept that there are at least two different subgroups accounting for BCCs in individuals below the age of 40?a group with single tumors whose incidence is increasing, presumably due to environmental factors, and a group with multiple tumors whose incidence is stable and who probably have hereditary predisposition to BCCs. The purpose of this study is to assess genetic and environmental risk factors for early onset BCCs and explore the interaction between these factors. This study is an outgrowth of our previous work showing that the PTCH gene underlies both hereditary and sporadic BCCs but applies and extends this work at a population level, with careful consideration of environmental contributions to the disease incidence. Five hundred cases with early onset BCC and 500 controls with benign skin conditions will be recruited from the Yale dermatopathology database for interviews and collection of biological samples. Questionnaire data will be used to assess potential environmental factors that might be related to the increased incidence, especially artificial tanning, excessive solar radiation exposure, smoking, and obesity. The interaction between these environmental variables and genetic variants of MC1R, known to relate to skin cancer susceptibility, will be assessed. Tumors from selected subjects in whom BCC risk appears to be related strongly to a particular environmental exposure will undergo sequencing of the PTCH gene to relate the reported exposure to "signature mutations" in DNA. Subjects with large numbers of BCCs or particularly early age of onset of BCCs will have detailed genetic studies to determine if they have a known hereditary disorder, and if not, to identify novel BCC predisposition genes. Risk factor data are needed to serve as a basis to guide preventive interventions. For example, strong evidence that tanning bed use is an important etiologic factor in early onset BCC, with supporting evidence showing mutational spectra consistent with UVB mutations, could form the basis for stronger legislation to prevent tanning bed use by minors. Alternatively, if smoking or other risk factors are more strongly associated, this suggests a different intervention strategy to reduce the disease. Identification of underlying predisposition genes may help target efforts at prevention to particular genetic subgroups. Thus, this etiologic work is highly and immediately translatable into preventive interventions aimed at reducing the incidence of this exceedingly common malignancy.

基底细胞癌（BCC）是美国最常见的恶性肿瘤；但是，已经 在流行病学研究中相对研究。时间趋势表明BCC发生率正在增加 总体而言，在年轻人，尤其是年轻女性中。来自“早期发作”案例的数据支持该概念 至少有两个不同的子组在40岁以下的个体中占BCC？ 单个肿瘤的发生率正在增加，大概是由于环境因素而引起的 有多个肿瘤的组，其发病率稳定并且可能具有遗传性倾向 BCC。这项研究的目的是评估早期发作BCC的遗传和环境风险因素 并探索这些因素之间的相互作用。这项研究是我们以前的工作的产物 PTCH基因是遗传和零星BCC的基础 人口水平，仔细考虑对疾病发病率的环境贡献。 五百例早期发作BCC和500例具有良性皮肤状况的对照将从 耶鲁大学皮肤病理学数据库，用于访谈和收集生物样品。问卷数据 将用于评估可能与发病率增加有关的潜在环境因素 特别是人工晒黑，过度的太阳辐射暴露，吸烟和肥胖。相互作用 在这些环境变量和MC1R的遗传变异之间，已知与皮肤癌有关 敏感性将进行评估。 BCC风险似乎与之相关的选定受试者的肿瘤 强烈地与特定的环境暴露会进行PTCH基因的测序以关联 报告暴露于DNA中的“签名突变”。大量BCC或尤其是 BCC的发病年龄将有详细的遗传研究，以确定它们是否具有已知的遗传性 疾病，如果没有，以鉴定新型的BCC易感基因。 风险因素数据需要作为指导预防干预措施的基础。例如，强 证据表明使用晒黑床是早期发作BCC的重要病因因素，并得到证据 显示与UVB突变一致的突变谱，可能是更强大立法的基础 防止未成年人使用晒黑床。另外，如果吸烟或其他危险因素更强烈 相关，这表明了减少疾病的不同干预策略。识别基础 易感基因可能有助于将预防努力靶向特定的遗传亚组。因此，这个 病因学高度高度可立即转化为预防干预措施，旨在减少该干预措施 这种极为常见的恶性肿瘤的发生率。