Molecular Epidemiology of t-MDS/AML

t-MDS/AML 的分子流行病学

• 批准号: 7214748
• 负责人: Sara S. Strom
• 金额: $ 7.28万
• 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 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7214748
• 关键词: ABCB1 gene; APEX1 gene; Aftercare; Age; Alkylating Agents; Alkylation; Base Excision Repairs; Blood; CYP3A4 gene; CYP3A5 gene; Cancer Center; Cancer Patient; Cancer Survivor; Cancer Survivorship; Carcinogen Metabolism; Carcinogens; Case-Control Studies; Characteristics; Chemical Exposure; Clinical; Combination Chemotherapy; Constitutional; DNA Repair Pathway; Data; Development; Diagnosis; Dose; Dysmyelopoietic Syndromes; ERCC2 gene; Enrollment; Epidemiologic Factors; Epidemiologic Studies; Ethnic Origin; Family history of; Future; GSTM1 gene; GSTP1 gene; GSTT1 gene; GSTT1 protein; Genes; Genetic; Genetic Markers; Genetic Polymorphism; Genetic Predisposition to Disease; Genotype; Incidence; Individual; Inherited; Institution; Lead; Life; Life Style; Malignant Neoplasms; Metabolism; Methodology; Modality; Molecular; Molecular Epidemiology; NAD(P)H dehydrogenase (quinone) 1, human; NQO1 gene; Nucleotide Excision Repair; Numbers; OGG1 gene; Occupational; Participant; Pathogenesis; Pathway interactions; Patients; Play; Population; Predisposing Factor; Predisposition; Radiation therapy; Recording of previous events; Recruitment Activity; Research; Risk; Risk Factors; Role; Second Primary Neoplasms; Smoke; Smoking; Standards of Weights and Measures; Syndrome; Testing; Therapy-Related Acute Myeloid Leukemia; University of Texas M D Anderson Cancer Center; Variant; XPA gene; XRCC1 gene; XRCC3 gene; cancer diagnosis; cancer therapy; cancer type; comparison group; drug metabolism; glutathione S-transferase M1; glutathione S-transferase pi; innovation; repaired; sex; treatment effect; treatment site

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（由申请方提供）：治疗相关急性髓性白血病和骨髓增生异常综合征（t-MDS/AML）是癌症治疗后个体的潜在长期并发症。t-MDS/AML的发病率正在增加，因为更多的癌症患者在更强化的治疗后存活更长时间。遗传易感性和流行病学因素在确定发生t-MDS/AML风险中的作用尚未确定。我们假设，特定的多态性参与代谢的致癌物质（如。GST、MPO、NQO 1、CYPP 2 E1）或DMA修复（例如，XRCC 1、XRCC 3、XPD）以及流行病学风险因素（例如吸烟、职业化学暴露）调节烷化剂和/或放疗治疗后发生t-MDS/AML的风险。本研究基于Strom博士进行的两项MDS和AML病例对照研究。我们建议进行一项病例比较研究，将300例已入组这些研究的t-MDS/AML患者与600例未发生第二种恶性肿瘤的患者进行比较，这些患者与我们的第一种原发性癌症类型和治疗沿着，并具有年龄、性别和种族。德州大学庞大的患者群体MD安德森癌症中心提供了招募和描述本研究所需患者的机会。整合遗传性遗传多态性、临床特征、家族史、人口统计学和生活方式因素的信息将为鉴定参与t-MDS/AML发病机制的因素提供独特的机会。增加我们对调节风险的因素的理解将使临床医生能够个性化治疗，以最大限度地减少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治疗相关恶性肿瘤的研究提供未来的假设，并可能导致癌症生存率的最终改善。