EPIDEMIOLOGY AND GENETICS OF EARLY ONSET BASAL CELL CARCINOMA

基底细胞癌（BCC）是美国最常见的恶性肿瘤;然而，它一直是 在流行病学研究中相对不足。时间趋势表明基底细胞癌的发病率正在增加 总体而言，在年轻人中，特别是在年轻女性中。来自"早发"病例的数据支持这一概念 在40岁以下的个体中，至少有两个不同的亚组负责BCC？一 单一肿瘤组，其发病率正在增加，可能是由于环境因素， 多发性肿瘤组，发病率稳定，可能有遗传倾向， BCC。本研究的目的是评估早发性基底细胞癌的遗传和环境危险因素 探索这些因素之间的相互作用。这项研究是我们以前工作的结果， PTCH基因是遗传性和散发性基底细胞癌的基础，但它适用于并扩展了这项工作， 人口水平，并仔细考虑环境因素对疾病发病率的影响。 500例早发性基底细胞癌患者和500例良性皮肤病对照者将从 耶鲁皮肤病理学数据库进行访问和收集生物样本。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。的相互作用 这些环境变量和MC1R的遗传变异之间的关系，已知与皮肤癌有关 敏感性，将进行评估。来自BCC风险似乎相关的选定受试者的肿瘤 强烈地暴露于特定环境的人将经历PTCH基因的测序， 报告称接触了DNA中的"特征突变"。具有大量BCC或特别是 早期年龄的BCC发病将有详细的遗传研究，以确定他们是否有已知的遗传 疾病，如果没有，以确定新的BCC易感基因。 需要风险因素数据作为指导预防性干预措施的基础。例如，强 有证据表明，晒黑床的使用是早发性基底细胞癌的一个重要病因，并有支持证据 显示与UVB突变一致的突变光谱，可以为更强有力的立法奠定基础， 防止未成年人使用日光浴床。或者，如果吸烟或其他风险因素更强烈， 相关的，这表明了一种不同的干预策略，以减少疾病。识别基础 易感基因可能有助于针对特定遗传亚群的预防工作。因此， 病原学工作高度和立即转化为预防性干预措施，旨在减少 这种极其常见的恶性肿瘤的发病率。

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.