Association between NAT2 polymorphisms and acute leukemia risk

Abstract

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Genotype-Environment Interaction Analysis of NQO1, CYP2E1, and NAT2 Polymorphisms and the Risk of Childhood Acute Lymphoblastic Leukemia: A Report From the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia

“…To our knowledge, no previous studies have explored the relationship between NAT2 genotypes and these environmental factors in ALL. However, differential contribution of single NAT2 SNPs to the risk of ALL has been observed recently by Zhu et al, who performed a meta-analysis including 1,522 acute leukemia patients and 2,688 controls (11).…”

“…Since ALL is considered a multifactorial disease where xenobiotics could be important factors that contribute to its pathogenesis, and that NQO1, CYP2E1 , and NAT2 are enzymes involved in the metabolism of xenobiotics (including benzene, cigarette smoking, chemotherapy agents, and alcohol drinking), which increase the risk to develop diverse human diseases ( 2 , 11 , 19 ), we used a MDR approach to identify combinations between genetic and environmental factors associated with ALL ( 29 ). Our data showed that the NAT2 _rs1799929- NAT2 _rs1208-ACMBP-MCMBP-PSFBC interact to increase the risk of ALL before pregnancy.…”

“…The polymorphisms NQO1 (rs1800566), CYP2E1 (rs3813867), and NAT2 [rs1041983 (C282T), rs1801280 (T341C), rs1799929 (C481T), rs1799930 (G590A), rs1208 (A803G), and rs1799931 (G857A)] were selected based on previous results in leukemia where they were the most consistently associated with leukemia risk ( 2 , 11 , 24 – 26 ). Association among alleles/genotypes and ALL was tested by comparing cases and controls.…”

“…The etiology is unclear; however, it has been recognized that the interaction between genetic and environmental factors may play a role in the development of the disease. It has been suggested that enzymes involved in the metabolism of carcinogenic agents are associated with ALL susceptibility; as well, it could explain the differences in survival rates reported across populations ( 9 – 11 ).…”

Study on Genotyping Polymorphism and Sequencing of N-Acetyltransferase 2 (NAT2) among Al-Ahsa Population

“…However, a Brazilian study demonstrated that NAT2 * 14, NAT2 * 5A, and NAT2 * 5C are correlated with an increased susceptibility to ALL in a Brazilian population [27,28]. Recently, a research group reviewed the published literature on the correlation between NAT2 genetic variants and susceptibility to acute leukemia and it was reported that rs1801280 (341T>C (NAT2 * 5)) contributes to the disease [29]. Having a high percentage of this NAT2 * 5A polymor-phism (23%) among Al-Ahsa community may make them vulnerable to acute leukemia, taking into account that the Eastern region is the second in the prevalence of leukemia in the Kingdom after Riyadh [30].…”