Significance of ATM Gene Polymorphisms in Chronic Myeloid Leukemia - a Case Control Study from India

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

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자료유형: 학술저널

저자정보: Gorre, Manjula (Department of Genetics, Osmania University) Mohandas, Prajitha Edathara (Department of Genetics, Osmania University) Kagita, Sailaja (Homibhabha Cancer Hospital and Research Centre) Cingeetham, Anuradha (Jawaharlal Nehru Technological University) Vuree, Sugunakar (Department of Genetics, Osmania University) Jarjapu, Sarika (Department of Genetics, Osmania University) Nanchari, Santhoshirani (Department of Genetics, Osmania University) Meka, Phanni Bhushann (Department of Genetics, Osmania University) Annamaneni, Sandhya (Department of Genetics, Osmania University) Dunna, Nageswara Rao (Shastra University) Digumarti, Raghunadharao (Homibhabha Cancer Hospital and Research Centre) Satti, Vishnupriya (Department of Genetics, Osmania University)

저널정보: 아시아태평양암예방학회 Asian Pacific journal of cancer prevention : APJCP Asian Pacific journal of cancer prevention : APJCP 제17권 제2호

발행연도: 2016.1

수록면: 815 - 821 (7page)

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Background: 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. Materials and Methods: 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). Results: 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. Conclusions: This study provides the first evidence of association of functional ATM gene polymorphisms with the increased risk of CML development as well as progression.

#Chronic myeloid leukemia #C4138T #EUTOS score #progression

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