Polymorphisms in XPC Provide Prognostic Information in Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is the most common type of adult leukemia for which cytosine arabinoside(Ara-C)-based chemotherapy is the main treatment. However, there is a significant difference in treatment response and survival, especially among large groups of patients with the same disease classification. Single nucleotide polymorphisms within the nucleotide excision repair pathway may alter the susceptibility of leukemia cells to chemotherapy. We investigated the role of six single nucleotide polymorphisms (ERCC5rs76871136, ERCC5rs77569659, ERCC5rs873601, XPCrs2228000, XPCrs2228001, and XPCrs1870134) within the nucleotide excision repair pathway on the outcome of patients with AML treated with cytosine arabinoside-based chemotherapy.

One hundred fifty-one patients with AML in a Chinese population were enrolled in this study. Patients diagnosed with other cancers or other hematological malignancies were excluded in this study. This study was approved by the ethics committee of Southeast University in compliance with Chinese guidelines for blood donation, and informed consent for genetic analysis was obtained from all participants according to the Declaration of Helsinki. All patients received Ara-C-based standard induction chemotherapy regimens. Patients were divided into three groups, according to cytogenetic risk. Moreover, the evaluation standard of these patients were evaluated by age(£40 years, 40–60 years, and ³60 years), WBC (>50 ′ 10⁹/L vs. £50 ′ 10⁹/L), hemoglobin level (>100 g/L vs. £100 g/L), and platelet count (>60 ′ 10⁹/L vs. £60 ′ 10⁹/L). Genotypes were determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Deviations from the Hardy–Weinberg equilibrium for genotypes and haplotype frequencies as well as haplotype–trait associations were assessed with Pearson's c² analysis using SHEsis. Once the expected number in any cell was less than five, demographic and clinical data across genotypes were compared using Pearson's c²analysis or Fisher's exact test. Significant genotypic differences among the different responders were calculated using Pearson's c²analysis. P <0.05 was considered statistically significant. We estimated the relative risk of responding to treatment with the genotypes as odds ratio(OR) and 95% confidence intervals(95%CI) using conditional logistic regression with adjustment for the effects of covariates. All statistical tests were two-sided and performed using SPSS 17.0.

Genotype frequencies for the polymorphisms were found to be in Hardy–Weinberg equilibrium. The results indicated that the distribution of three genotypes of XPCrs1870134 significantly differed among the cytogenetic risk groups (P = 0.04). The frequency of the CC genotype of XPCrs2228001 was significantly higher in male patients than in female patients (P = 0.03), whereas that of the CC genotype of XPCrs2228000 was significantly higher in patients with a hemoglobin level of 100 g/L or less compared with those who had a hemoglobin level greater than 100 g/L (P = 0.039).Moreover, patients carrying at least one variant allele (XPCrs2228001AA+CC) were more likely to respond better than those who did not carry a variant. However, no significant association was detected between polymorphisms in ERCC5 and treatment response.

These findings suggest that XPC polymorphisms are important markers for the outcome of patients with AML in the Chinese population.

No relevant conflicts of interest to declare.