Genetic Polymorphisms in Myeloma

描述(申请人提供)：尽管多发性骨髓瘤在临床上被定义为在骨髓中积聚克隆性、恶性浆细胞，但该疾病在进展和治疗反应方面表现出显著的异质性。该方案提出的假设是，功能性基因多态性与肿瘤生长控制、药物代谢/解毒以及DNA修复机制有关，这些机制将影响化疗毒性和疾病的病程。东方合作肿瘤组3期临床试验的细胞库和DNA库将被用来确定与药物代谢/运输相关的基因(细胞色素P450、髓过氧化物酶、谷胱甘肽S转移酶(M、T、P)、多药耐药1)、DNA修复(XRCC1、ERCC2)以及骨髓瘤相关生长因子(IL-6、IL-1b、IL-1RA、IL-10、TNA、LTA、TGFb)的等位基因频率。已知的改变这些基因产物功能的遗传多态将与生存、骨病、毒性、反应、感染和继发性恶性肿瘤相关。这些相关性将提供重要的遗传标记，使更好的个体化治疗策略成为可能。

DESCRIPTION (provided by applicant): Although multiple myeloma is clinically defined as the accumulation of clonal, malignant plasma cells in the bone marrow, the disease shows significant heterogeneity with regard to progression and therapeutic response. The hypothesis addressed in this proposal is that functional genetic polymorphisms are associated with tumor growth control, drug metabolism/detoxification, and DNA repair mechanisms that will influence chemotoxicity and the course of the disease. Cell and DNA banks from 3 phase Ill clinical trials of the Eastern Cooperative Oncology Group will be used to determine allelic frequencies of genetic polymorphisms in genes associated with drug metabolism/transport (cytochrome P450, myeloperoxidase, glutathione S-transferases (M,T,P), multi-drug resistance 1); DNA repair (XRCCC1, ERCC2); and, myeloma related growth factors (lL-6, IL-1b, IL-1RA, IL-10, TNa, Lta, TGFb). Known genetic polymorphisms that alter function of each of these gene products will be correlated with survival, bone disease, toxicity, response, infection, and secondary malignancies. These correlations will provide important genetic markers that will allow better individualized treatment strategies.