[Polymorphisms of RAD51(G135C) and XRCC3(C241T) genes and correlations thereof with prognosis and clinical outcomes of acute myeloid leukemia].
OBJECTIVE
To investigate the impacts of RAD51G(135C) and XRCC3(C241T) genotypes on the response, adverse effects, and prognosis of acute myelocytic leukemia (AML).


METHODS
RAD51(G135C), XRCC3(C241T), GSTT1, and GSTM1 genotypes were analyzed in 372 patients with AML, 226 males and 146 females, by PCR-RFLP or PCR. The Complete remission (CR) rate, adverse effects, overall survival (OS), and relapse-free survival (RFS) were compared among the groups with different genotypes.


RESULTS
(1) During the induction chemotherapy, XRCC3(C241T) polymorphic allele was significantly associated with the shorter survival of the AML patients with t (15; 17)/PML-RARalpha (OR = 8.750, P = 0.046). Among the non-M3 patients, the complete remission (CR) rate of those with double RAD51(G135C) and GSTT1 wild genotypes was 71.6%, significantly higher than that of those not with double RAD51(G135C) and GSTT1 wild genotypes (54.4%, P = 0.028). (2) The OS of the non-M3 AML patients with double RAD51(G135C) and GSTT1 wild genotypes was (39.1 +/- 7.1) months, significantly longer than those with double variant types [(22.4 +/- 3.2) months, P = 0.042]. The relapse-free survival (RFS) of the M4EO and M2 patients with double XRCC3(C241T) and GSTT1 wild type genotype were 48.3 months and 56.5 months, both significantly longer than those of the patients with double variant genotypes (28.8 months and 10.0 months respectively, both P < 0.05). The OS of the M2 patients with triple RAD51(G135C), GSTT1, and GSTM1 variant genotypes was (22.4 +/- 3.2) months, significantly shorter than those with triple RAD51(G135C), GSTT1, and GSTM1 wild genotypes [(39.1 +/- 7.1) months, P = 0.042]. The RFS of the M2 patients with triple RAD51(G135C), GSTT1, and GSTM1 variant genotypes was 10.0 months, significantly shorter than that of the patients with triple RAD51(G135C), GSTT1, and GSTM1 wild genotypes (64.2 months, P = 0.015). (3) The risk levels of neutropenia, nausea and vomiting, and alopecia of the patients with variant XRCC3(C241T) genotype were all significantly higher than those of the wild type genotype (all P < 0.05). The risk of hematuria of the patients with variant genotype was significantly higher than that of the patients with wild genotype (P = 0.017).


CONCLUSIONS
The polymorphisms of XRCC3(C241T) and RAD51(G135C) genes are significantly related to response to therapy, adverse effects, and prognosis of AML. Detection of the XRCC3(C241T) and RAD51(G135C) genotypes may be useful in selecting individual chemotherapy regimens for patients with AML.
Liu
Liang
L
Institute of Hematology, Chinese Academe of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.
Yang
Lin
L
Zhang
Yue
Y
Xu
Ze-Feng
ZF
Yu
Ming-Hua
MH
Wang
Jian-Xiang
JX
Xiao
Zhi-Jian
ZJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011379:Prognosis; D051135:Rad51 Recombinase / Q000235:genetics*; D012074:Remission Induction; D016019:Survival Analysis; D055815:Young Adult
D004268:DNA-Binding Proteins; C110901:X-ray repair cross complementing protein 3; D051135:Rad51 Recombinase