N-Acetyltransferase 2 (Nat2) Single Nucleotide Polymorphisms In Patients With Adult Acute Myeloid Leukemia (Non-M3): A Case-Control Study

Background: Acute myeloid leukemia (AML) is a heterogeneous hematological malignant cancer. N-acetyltransferase 2 (NAT2) is a carcinogen-metabolizing gene involved in both carcinogen detoxification and activation. The purpose of this study was to explore the association between NAT2 polymorphisms and AML.Methods: A total of 98 AML patients and 1993 healthy controls were included in this case-control study. Odds ratios (ORs) and 95% confidential intervals (95%CIs) derived from unconditional logistic regression models were used to estimate the relative risk of AML for NAT2 SNPs. The prognosis of NAT2 SNPs in AML patients was analyzed using the Kaplan-Meier method.Results: We found NAT2 rs1799930 GG, GA, and AA genotype in 59.2%, 34.7%, and 6.1% AML patients and in 47%, 42.5%, and 10.4% controls (P < 0.05). NAT2 rs1799931 GG, GA, and AA genotype in 50%, 43.9%, and 6.1% AML patients and in 66.3%, 30%, and 3.7% controls (P = 0.01). NAT2*5B mutated haplotype in 1.2% AML patients and in 4.4% controls (P = 0.03). In non-smokers and non-drinkers population, NAT2 rs1799930 AA genotype was associated with a decreased risk of AML compared with the GG genotype (P < 0.05). Mutated haplotype NAT2*6A linked with lower risk of AML compared with the wild type haplotype NAT2*4 (P = 0.03). Patients with NAT2 slow acetylation phenotype were related to lower prevalence of AML. During the 106-month follow-up, there was no statistically significant difference in overall survival (OS) or disease-free survival (DFS) of AML patients with different NAT2 genotypes.Conclusion: Our findings suggested that the frequencies of NAT2 rs1799930 genotype, rs1799931 genotype, and NAT2*5B haplotype were significantly different between AML patients and healthy controls. Individuals with NAT2 rs1799930 AA homozygous mutated genotype, NAT2*6A mutated haplotype, and NAT2 slow acetylation phenotype may relate to lower risk of AML.