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Functional polymorphisms in the NBS1 gene and acute lymphoblastic leukemia susceptibility in a Chinese population

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Abstract

As a component of the MRN complex (which is a heterotrimeric protein complex consisting of MRE11, RAD50 and NBS1), NBS1 plays an important role in cellular response to DNA damage and the maintenance of chromosomal integrity. Leukemia is common in NBS1 germ line–mutated patients. The NBS1 E185Q polymorphism (8360G>C, rs1805794) has been frequently studied in some cancers with discordant results, but its association with acute lymphoblastic leukemia (ALL) in Chinese population has not been investigated. Besides, there is no report about the association between NBS1 3′UTR variant rs2735383 and ALL risk. In this study, a multiple centre case–control analysis was performed to assess the association between NBS1 polymorphisms and ALL risk. The genotypes and haplotypes were determined in 175 cases and 350 controls, and the associations with risk of ALL were estimated by logistic regression. We observed significant difference in genotype frequencies at the rs1805794 C/G site between cases and controls (Ptrend < 0.0001). The allele C increases the risk of ALL in a dose-dependent response manner. These findings suggest that E185Q polymorphism in NBS1 may be a genetic modifier for developing ALL.
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Keywords: ALL; NBS1; polymorphism

Document Type: Research Article

Affiliations: Laboratory of Cellular and Molecular Tumor Immunology, Department of Hematology, Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China

Publication date: March 1, 2011

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