Molecular Epidemiology of t-MDS/AML

t-MDS/AML 的分子流行病学

• 批准号: 7115097
• 负责人: Sara S. Strom
• 金额: $ 7.5万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7115097
• 关键词: alkylating agents; clinical research; epidemiology; neoplasm /cancer; neoplasm /cancer therapy; play; role

DESCRIPTION (provided by applicant): Treatment-related acute myeloid leukemia and myelodyplastic syndrome (t-MDS/AML) are potential long- term complications in individuals after cancer therapy. The incidence of t-MDS/AML is increasing as more cancer patients are surviving longer following more intensive treatments. The role that genetic susceptibility and epidemiologic factors play in determining risk of developing t-MDS/AML has not been established. We hypothesize that specific polymorphisms involved in the metabolism of carcinogens (eg. GSTs, MPO, NQO1, CYPP2E1) or in DMA repair (eg. XRCC1, XRCC3, XPD), as well as epidemiological risk factors( e.g. smoking, occupational chemical exposures) modulate the risk of developing t-MDS/AML after treatment with alkylating agents and/or radiotherapy. This study builds upon two MDS and AML case-control studies conducted by Dr. Strom. We propose to conduct a case-comparison study to compare 300 t-MDS/AML patients already enrolled in these studies to 600 patients who have not developed second malignancies and are matched to our cases on first primary cancer type and treatment along with age, sex, and ethnicity. The large patient population at U.T. MD Anderson Cancer Center provides the opportunity to recruit and characterize the patients necessary to make this study possible. Integrating information on inherited genetic polymorphisms, clinical characteristics, family history, demographic and lifestyle factors will provide a unique opportunity for the identification of factors involved in t-MDS/AML pathogenesis. Increasing our understanding of factors that modulate risk will allow clinicians to individualize treatments to minimize long-term risk of t-MDS/AML while still providing effective cancer treatment. We believe that this study will provide future hypotheses for research into treatment- related malignancies, and may lead to eventual improvements in cancer survivorship.

描述（由申请人提供）：治疗相关的急性髓系白血病和骨髓增生异常综合征（t-MDS/AML）是癌症治疗后个体潜在的长期并发症。t-MDS/AML的发病率正在增加，因为越来越多的癌症患者在接受更强化的治疗后存活时间更长。遗传易感性和流行病学因素在决定发生t-MDS/AML风险中的作用尚未确定。我们假设与致癌物代谢有关的特定多态性(例如：gst， MPO, NQO1, CYPP2E1)或DMA修复(例如：XRCC1、XRCC3、XPD)以及流行病学危险因素（如吸烟、职业性化学品暴露）调节烷基化剂治疗和/或放疗后发生t-MDS/AML的风险。这项研究建立在Strom博士进行的两项MDS和AML病例对照研究的基础上。我们建议开展一项病例比较研究，将300名已经参加这些研究的t-MDS/AML患者与600名未发生第二恶性肿瘤的患者进行比较，这些患者与我们的病例在原发癌症类型和治疗以及年龄、性别和种族方面相匹配。德州大学MD安德森癌症中心的庞大患者群体为招募和描述使这项研究成为可能所必需的患者提供了机会。整合遗传多态性、临床特征、家族史、人口统计学和生活方式因素的信息将为识别t-MDS/AML发病机制的相关因素提供独特的机会。增加我们对调节风险因素的理解将使临床医生能够个性化治疗，以最大限度地降低t-MDS/AML的长期风险，同时仍然提供有效的癌症治疗。我们相信这项研究将为未来治疗相关恶性肿瘤的研究提供假设，并可能最终导致癌症生存率的提高。