Meta-analysis of the relationship between slow acetylation of N-acetyl transferase 2 and the risk of bladder cancer

Abstract

ABSTRACT. The incidence of bladder cancer is closely associated with exposure to aromatic amines, that can cause cancer only after metabolic activation regulated by N-acetyl transferase 1 and 2 (NAT1 and NAT2). Many studies have indicated that slow acetylation of NAT2 increases the risk of bladder cancer. The major risk factor is tobacco smoke; however, some studies have failed to prove this. This study attempted to explore the correlation between NAT2 slow acetylation and bladder cancer risk through a meta-analysis of published case-control studies. Studies detecting NAT2 gene status in bladder cancer patients and healthy controls were retrieved ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 16896-16904 (2015) 16897 N-acetyl transferase 2 and bladder cancer ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 16896-16904 (2015) from PubMed, Cochrane, EMchrane, CBM, and CNKI. We retrieved the data of cited articles and publications to identify and compare NAT2 gene in bladder cancer patients and healthy controls. The variables within and between the studies were also considered. The META module in the Stata v.6.0 software was used for data analysis. Twenty independent studies were enrolled in our meta-analysis according to the inclusion and exclusion criteria. Individual differences in the bladder cancer susceptibility were, in part, attributed to the effect of carcinogens. The merged odds ratio of the effect of slow acetylation on bladder cancer was 1.31 (95% confidence interval = 1.11-1.55). In conclusion, NAT2 slow acetylation state was associated with bladder cancer risk, and was shown to modestly increase the risk of bladder cancer.

Revisiting Histone Deacetylases in Human Tumorigenesis: The Paradigm of Urothelial Bladder Cancer

“…Interestingly, a genetic predisposition to bladder cancer has been previously reported, involving genes that control carcinogen metabolism, such as N -acetyltransferase 2 ( NAT2 ). Moreover, genome-wide association studies (GWAS) have identified sequence variants that can increase susceptibility to the disease, with alterations in the urea transporter SLC14A1 gene being characteristic examples [5,14,15,16,17,18,19,20,21,22,23].…”

New Progress of Epigenetic Biomarkers in Urological Cancer

“…A study in 2011 identified global histone H4K20 trimethylation that could predict cancer-specific survival in patients with muscle-invasive bladder cancer [28]. A meta-analysis published by An et al showed that merged odds ratio of the effect between slow acetylation and bladder cancer was 1.31 (95% confidence odds ratio interval = 1.11–1.55), illustrating that slow acetylation modestly increases the risk of bladder cancer [29]. Recently, Jia et al found that the acetylation status of KLF4 can decide the gene function as a tumor suppressor or oncogene in bladder cancer.…”

Human N-acetyltransferase 2 (NAT2) gene variability in Brazilian populations from different geographical areas

“…The influence of NAT2 genetic variability to the acetylation phenotype and, consequently, to the therapeutic outcomes of those drugs has been demonstrated for several disease models, including for tuberculosis and hypertension among others ( Possuelo et al, 2008 ; Teixeira et al, 2011 ; Spinasse et al, 2014 ). Moreover, NAT2 variability has been investigated as a possible risk factor for xenobiotic-related susceptibility to Alzheimer’s disease, schizophrenia, diabetes, cataract, and parkinsonism ( Bialecka et al, 2002 ; Agúndez et al, 2008 ; Luan et al, 2017 ), while it is also linked to urinary bladder and colorectal cancers ( García-Closas et al, 2005 ; An et al, 2015 ).…”