MELANOMA AND ALLELIC VARIATION IN THE MCIR GENE

描述：（申请人的描述）我的学术生涯目标之一是 开展分子和遗传流行病学研究， 色素性病变相关因素，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 黑色素瘤的基因可以帮助识别那些风险增加的人 疾病，并可能导致增加公共和个人的努力， 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已经达到流行病的比例和死亡率 在过去的几十年里，黑色素瘤的发病率缓慢上升。 预防 肿瘤学学术奖将给我一个机会，成为一个称职的 黑素瘤分子流行病学家。 为此，我将推进我的学术 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。 将通过参与分子生物学实验获得实践经验。 实验室生物学，重点是分子生物学中使用的方法 流行病学 两个研究项目被提出来探索候选人的关联 易感基因与黑色素瘤发生 候选人的突变 黑皮质素-1受体（MC1R）可能影响黑色素 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患者中基因变异的数量和类型 和单一皮肤黑色素瘤（SCM），以及ii）测试这些突变是否 在MPM的后续发展中发挥作用。 结果将有助于 对候选易感基因的流行病学文献有很大帮助， 与黑色素瘤相关，将有助于重点关注一级和二级预防 对于继发性和原发性黑色素瘤风险增加的人。 第二 项目评估MC1R基因中的等位基因变异是否解释了 黑色素瘤家族中的黑色素瘤模式。 本项目的成果 可能提供有价值的洞察遗传易感性黑色素瘤看到 在某些家庭中，可能会导致更有效的机制， 在这些家庭中进行预防和临床随访。

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.