Association between NAT2 genetic polymorphism and osteosarcoma susceptibility

Objective: This study was conducted to investigate the association between N-acetyltransferase 2 (NAT2) gene polymorphism and the susceptibility to osteosarcoma (OS) and to explore the functional activity significance of NAT2 gene polymorphism in OS susceptibility. Methods: 283 cases of OS were selected as the OS group, and 264 subjects who received health examination in The Third People's Hospital of Qingdao during January 2012 and September 2014 were selected as the control group. Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) was applied to identify the NAT2 gene polymorphism, and SPSS 21.0 software was applied for data analyses. Results: Four types of WT, M1, M2 and M3 NAT2 alleles were identified among the 283 OS patients, including the rapid acetylators genotype and the slow acetylators genotype. The frequencies of NAT2 genotypes (homozygous wild-type WT/WT, heterozygous mutant WT/Mx, homozygous mutant Mx/Mx) were 36.36%, 51.14%, and 12.50% in the control group, and 47.35%, 45.23%, and 7.42% in the OS group, and the frequencies of the two groups were significantly different (all P < 0.05). The frequencies of the four alleles were not significantly different between the two groups (all P > 0.05). The frequency of the rapid acetylators genotype in the OS group was significantly higher than that of the control group (92.58% vs. 87.50%), while the frequency of the slow acetylators genotype in the control group was significantly lower than that of OS group (7.42% vs. 12.50%, chi(2) = 3.961, P < 0.05). Patients with the rapid acetylators genotype was 1.782 times higher in risk of OS formation than patients with the slow acetylators genotype (95% CI = 1.003 +/- 3.168, P < 0.05). The OS patients with the rapid acetylators genotype had bigger tumor size (OR = 3.706, 95% CI = 1.007 similar to 9.396, P = 0.039), lower tumor differentiation (OR = 3.350, 95% CI = 1.192 similar to 9.414, P = 0.016), and higher transitivity (OR = 5.116, 95% CI = 1.917 similar to 13.65, P < 0.001) compared with those with the slow acetylators genotype. Age, gender, tumor location were not significantly different (all P > 0.05). Conclusion: NAT2 gene polymorphism may be associated with OS susceptibility, and NAT2 rapid acetylators genotype may be a risk factor for OS.