Genetic variations of DNA repair genes and their prognostic significance in patients with acute myeloid leukemia.
Common genetic variations in genes involved in DNA repair or response to genotoxic stress may influence both cancer susceptibility and treatment response individually or interactively. However, in acute myeloid leukemia (AML), the relevance of these genetic variations remains to be fully established. In this study, we analyzed 42 genetic variations among 15 candidate genes in 307 AML patients and 560 age-sex matched controls. Their associations with chemotherapy response were further evaluated in combination with other well-established prognostic factors. An increased risk of AML was found in individuals heterozygous for XPD 2251A>C (rs13181) with an odds ratio (OR) of 1.637 (95% confidence interval [CI]: 1.118-2.395), and the increased risk could be attributed to C allele (OR = 1.505, 95% CI: 1.061-2.134). Postchemotherapy response analysis revealed that AML patients heterozygous for ATM 4138C>T (rs3092856) or GG homozygous for TP53 215C>G (rs1042522) were independently linked to inferior treatment outcomes. These results uncover novel prognostic factors for AML patients treated with chemotherapy and may also indicate an etiological role of XPD in this disease.
State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Jing-Yi
JY
Shi
Zhi-Hong
ZH
Ren
Bo
B
Jiao
Run
R
Xiao
Hai-Yang
HY
Yun
Bing
B
Chen
Wei-Li
WL
Zhao
Qi
Q
Zhu
Zhu
Z
Chen
Sai-Juan
SJ
Chen
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics; D055815:Young Adult
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D051759:Xeroderma Pigmentosum Group D Protein