Gorre Manjula, Mohandas Prajitha Edathara, Kagita Sailaja, Cingeetham Anuradha, Vuree Sugunakar, Jarjapu Sarika, Nanchari Santhoshirani, Meka Phanni Bhushann, Annamaneni Sandhya, Dunna Nageswara Rao, Digumarti Raghunadharao, Satti Vishnupriya
Department of Genetics, Osmania University, Hyderabad, India E-mail :
Asian Pac J Cancer Prev. 2016;17(2):815-21. doi: 10.7314/apjcp.2016.17.2.815.
Development of chronic myeloid leukemia (CML) involves formation of double strand breaks (DSBs) which are initially sensed by the ataxia telangiectasia mutated (ATM) signal kinase to induce a DNA damage response (DDR). Mutations or single nucleotide polymorphisms in ATM gene are known to influence the signaling capacity resulting in susceptibility to certain genetic diseases such as cancers.
In the present study, we have analyzed -5144A>T (rs228589) and C4138T (rs3092856) polymorphisms of theATM gene through polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) in 925 subjects (476 CML cases and 449 controls).
The A allele of -5144A>T polymorphism and T allele of C4138T polymorphism which were known to be influencing ATM signaling capacity are significantly associated with enhanced risk for CML independently and also in combination (evident from the haplotype and diplotype analyses). Significant elevation in the frequencies of both the risk alleles among high risk groups under European Treatment and Outcome Study (EUTOS) score suggests the possible role of these polymorphisms in predicting the prognosis of CML patients.
This study provides the first evidence of association of functional ATM gene polymorphisms with the increased risk of CML development as well as progression.
慢性髓性白血病（CML）的发生涉及双链断裂（DSB）的形成，其最初由共济失调毛细血管扩张突变（ATM）信号激酶感知以诱导DNA损伤反应（DDR）。已知ATM基因中的突变或单核苷酸多态性会影响信号传导能力，从而导致对某些遗传性疾病如癌症的易感性。
在本研究中，我们通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析了925名受试者（476例CML病例和449名对照）中ATM基因的-5144A>T（rs228589）和C4138T（rs3092856）多态性。
已知会影响ATM信号传导能力的-5144A>T多态性的A等位基因和C4138T多态性的T等位基因分别独立以及联合起来均与CML风险增加显著相关（从单倍型和双倍型分析中可见）。欧洲治疗与结果研究（EUTOS）评分下高危组中两种风险等位基因的频率显著升高，表明这些多态性在预测CML患者预后方面可能发挥的作用。
本研究首次提供了功能性ATM基因多态性与CML发生及进展风险增加之间存在关联的证据。
