Voso M T, Fabiani E, D'Alo' F, Guidi F, Di Ruscio A, Sica S, Pagano L, Greco M, Hohaus S, Leone G
Istituto di Ematologia, Universita' Cattolica del Sacro Cuore, Roma, Italy.
Ann Oncol. 2007 Sep;18(9):1523-8. doi: 10.1093/annonc/mdm191.
Polymorphisms in genes involved in detoxification and DNA-repair pathways may modify the individual's risk for genomic damage, and, as a consequence, the risk of developing malignant diseases.
We performed a case-control study including 160 cases of acute myeloid leukaemia (AML) and 162 matched controls to test the impact of six genomic polymorphisms on the risk to develop AML and/or therapy-related AML.
We found a significantly higher prevalence of the polymorphic variants RAD51-G135C and CYP3A4-A-290G genes in AML cases, when compared with controls (P = 0.02 and P = 0.04), increasing the risk of AML 2.1-folds (95% CI: 1.1-4.0) and 3.2-fold (95% CI: 1.1-11.5), respectively. Carriers of both the RAD51-G135C and CYP3A4-A-290G variants were at highest AML risk (P = 0.003; OR:13,6; 95% CI: 2.0-585.5), suggesting a synergistic effect between these polymorphisms.
These results suggest that polymorphic variants in DNA-repair and detoxification enzymes may co-operate in modulating the individual's risk of AML.
参与解毒和DNA修复途径的基因多态性可能会改变个体发生基因组损伤的风险，进而影响患恶性疾病的风险。
我们开展了一项病例对照研究，纳入160例急性髓系白血病（AML）患者和162例匹配的对照，以检测6种基因多态性对发生AML和/或治疗相关AML风险的影响。
与对照组相比，我们发现AML患者中RAD51-G135C和CYP3A4-A-290G基因多态性变体的患病率显著更高（P = 0.02和P = 0.04），分别使AML风险增加2.1倍（95% CI：1.1 - 4.0）和3.2倍（95% CI：1.1 - 11.5）。RAD51-G135C和CYP3A4-A-290G变体的携带者发生AML的风险最高（P = 0.003；OR：13.6；95% CI：2.0 - 585.5），表明这些多态性之间存在协同效应。
这些结果表明，DNA修复和解毒酶中的多态性变体可能共同调节个体患AML的风险。
