MELANOMA AND ALLELIC VARIATION IN THE MCIR GENE

黑色素瘤和 MCIR 基因中的等位基因变异

• 批准号: 6044831
• 负责人: PETER A KANETSKY
• 金额: $ 12.18万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-06 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6044831
• 关键词: alleles; clinical research; family genetics; gene mutation; genetic polymorphism; genetic susceptibility; hormone receptor; human subject; linkage mapping; melanoma; neoplasm /cancer genetics; ultraviolet radiation

DESCRIPTION: (Applicant's Description) One of my academic career goals is to develop molecular and genetic epidemiologic research to identify etiologic factors associated with pigmented lesions, including cutaneous malignant melanoma and multiple primary melanoma (MPM). Determination of susceptibility genes for melanoma can facilitate identification of those at increased risk for disease and may result in increase public and individual efforts of prevention and early detection. The potential impact of these measures is great, as melanoma incidence has reached epidemic proportions and mortality due to melanoma has slowly increased over the past decades. The Preventive Oncology Academic Award will give me an opportunity to become a competent melanoma molecular epidemiologist. To this end, I will advance my academic understanding of melanoma through further education in the basic sciences, molecular biology/epidemiology, genetics, and clinical decision making. Practical experience will be gained through participation in molecular laboratory biology, with a focus on methodologies used in molecular epidemiology. Two research projects are proposed to explore the association of a candidate susceptibility gene and development of melanoma. Mutations in the candidate gene of interest, the melanocortin-1 receptor (MC1R), may affect melanin synthesis, resulting in an increased potential for cellular DNA damage that may lead to melanocytic carcinogenesis. The goals of the first study are i) to determine the number and types of gene variants among persons with MPM and single cutaneous melanoma (SCM), and ii) to test whether these mutations play a role in the subsequent development of MPM. The results will contribute greatly to the epidemiologic literature on candidate susceptibility genes associated with melanoma and will help focus primary and secondary prevention for persons at increased risk for secondary, primary melanomas. The second project evaluates whether allelic variants in the MC1R gene explain the pattern of melanoma in families prone to melanoma. Result from this project may provide valuable insight into the genetic predisposition to melanoma seen in some families, and may lead to more efficient mechanisms of primary prevention and clinical follow-up within these families.

描述：（申请人的描述）我的学术职业目标之一是 开展分子和遗传流行病学研究以确定病因 与色素病变相关的因素，包括皮肤恶性 黑色素瘤和多原发性黑色素瘤（MPM）。 敏感性测定 黑色素瘤基因有助于识别高风险人群 疾病，并可能导致公众和个人加大努力 预防和早期发现。 这些措施的潜在影响是 很好，因为黑色素瘤的发病率和死亡率已达到流行病的程度 由于黑色素瘤在过去几十年中缓慢增加。 预防性 肿瘤学学术奖将使我有机会成为一名有能力的人 黑色素瘤分子流行病学家。 为此，我将进一步提高我的学业水平 通过基础科学的进一步教育了解黑色素瘤， 分子生物学/流行病学、遗传学和临床决策。 通过参与分子生物学将获得实践经验 实验室生物学，重点是分子生物学中使用的方法 流行病学。 提出了两个研究项目来探索候选人的关联 易感基因与黑色素瘤的发生。 候选人的突变 感兴趣的基因，黑皮质素-1 受体 (MC1R)，可能会影响黑色素 合成，导致细胞 DNA 损伤的可能性增加 可能导致黑素细胞癌变。 第一项研究的目标是 i) 确定 MPM 患者基因变异的数量和类型 和单皮肤黑色素瘤 (SCM)，以及 ii) 测试这些突变是否 对MPM的后续发展起到一定的作用。 结果将做出贡献 极大地依赖于候选易感基因的流行病学文献 与黑色素瘤相关，有助于集中一级和二级预防 对于继发性、原发性黑色素瘤风险较高的人。 第二个 该项目评估 MC1R 基因中的等位基因变异是否可以解释 黑色素瘤家族易患黑色素瘤的模式。 该项目的结果 可能为了解黑色素瘤的遗传易感性提供有价值的见解 在一些家庭中，可能会导致更有效的初级机制 这些家庭内的预防和临床随访。