title: RAD51 and XRCC3 polymorphisms: impact on the risk and treatment outcomes of de novo inv(16) or t(16;16)/CBFβ-MYH11(+) acute myeloid leukemia.
abstract: DNA double-strand break repair via homologous recombination (HR) is essential in maintaining genetic integrity, and may modulate susceptibility to the development of acute myeloid leukemia (AML) and influence outcomes of AML. This study was designed to evaluate the effects of polymorphisms in HR repair genes RAD51 and XRCC3 on the risk and treatment outcomes of inv(16)/t(16;16)/CBFβ-MYH11(+) AML. The distribution of polymorphisms in RAD51-G135C and XRCC3-Thr241Met were studied by PCR-RFLP analysis in 625 cases of de novo AML, including 105 cases with inv(16)/t(16;16)/CBFβ-MYH11, 806 family controls and 704 volunteer controls. It was found that the XRCC3-241Met variant significantly increased the risk of the development of the AML with inv(16)/t(16;16) as compared with both the volunteer control (OR=7.22; 95% CI, 4.37-11.91) and the family control (OR=7.99; 95% CI, 5.03-12.69). A retrospective study conducted in 103 inv(16)/t(16;16) AML patients. In multivariate analysis for the potential prognostic factors, the XRCC3-241Met variant significantly reduced disease-free survival (DFS) in complete remission (CR) achieved patients (HR=2.34, 95% CI, 1.32-4.16). These data indicate that the XRCC3-241Met variant may not be only a susceptibility factor to the AML with inv(16)/t(16;16), but also an independent poor-prognostic factor for this AML subtype.
authors.affiliation: State Key Laboratory of Experimental Hematology, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Liu
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.forename: Yingchang
authors.initials: Y
authors.lastname: Mi
authors.forename: Jianxiang
authors.initials: J
authors.lastname: Wang
authors.forename: Jianyong
authors.initials: J
authors.lastname: Li
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiaotang
authors.initials: X
authors.lastname: Ma
authors.forename: Tiejun
authors.initials: T
authors.lastname: Qin
authors.forename: Zefeng
authors.initials: Z
authors.lastname: Xu
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Xiao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D007446:Chromosome Inversion; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D051135:Rad51 Recombinase / Q000235:genetics*; D012189:Retrospective Studies; D015996:Survival Rate; D014178:Translocation, Genetic; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C095514:CBFbeta-MYH11 fusion protein; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D015514:Oncogene Proteins, Fusion; C110901:X-ray repair cross complementing protein 3; C495153:RAD51 protein, human; D051135:Rad51 Recombinase