Haplotype of<i>N</i>-Acetyltransferase 1 and 2 and Risk of Pancreatic Cancer

Jiao, Li; Doll, Mark A.; Hein, David W.; Bondy, Melissa L.; Hassan, Manal M.; Hixson, James E.; Abbruzzese, James L.; Li, Donghui

doi:10.1158/1055-9965.epi-06-0992

Cited by 29 publications

(26 citation statements)

References 35 publications

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“…Consequently, studies relating NAT2 and pancreatic cancer susceptibility should be carried out in Asia. Of the studies analyzed in this meta-analysis, three divided the patients into three phenotypes (rapid, intermediate, and slow) (Li et al, 2006;Jiao et al, 2007;Suzuki et al, 2008) whereas the other three studies only discriminated two phenotypes (rapid and slow) (Bartsch et al, 1998;Li et al, 2002;Ayaz et al, 2008). As we did not know what methods to use to represent the intermediate phenotype category in the two-phenotype studies, only the data of the rapid or slow phenotype individuals were taken from the first group of studies and compared to all subjects.…”

Section: Discussionmentioning

confidence: 99%

“…After reviewing the full texts, four studies were excluded following our search terms (Gross et al, 1999;Agundez, 2008;Brand et al, 2010;Jang et al, 2012). Finally, we identified six studies for the meta-analysis (Bartsch et al, 1998;Li et al, 2002Li et al, , 2006Jiao et al, 2007;Ayaz et al, 2008;Suzuki et al, 2008). Detailed characteristics of these studies are provided in Table 1.…”

Section: Systematic Reviewmentioning

confidence: 99%

“…In the control group, 236 were rapid, 529 were intermediate, and 917 were slow. The study locations included three studies performed in United States (Li et al, 2006;Jiao et al, 2007;Suzuki et al, 2008), one in Turkey (Ayaz et al, 2008), and two multi-center studies (Bartsch et al, 1998;Li et al, 2002). Regarding the division of NAT2 phenotypes, three studies utilized three phenotypes (rapid, intermediate, and slow) (Li et al, 2006;Jiao et al, 2007;Suzuki et al, 2008) and other three studies divided the phenotypes into two categories (rapid and slow) (Bartsch et al, 1998;Li et al, 2002;Ayaz et al, 2008).…”

Section: Systematic Reviewmentioning

confidence: 99%

“…In the meta-analysis, six studies were included that examined the association between the NAT2 polymorphism associated with rapid acetylation genotypes and pancreatic cancer risk (Bartsch et al, 1998;Li et al, 2002Li et al, , 2006Jiao et al, 2007;Ayaz et al, 2008;Suzuki et al, 2008). The study-specific RRs for the NAT2 polymorphism associated with rapid acetylation genotypes ranged from 0.56 to 1.23.…”

Section: Rapid Acetylation Genotypesmentioning

confidence: 99%

“…Since Bartsch et al (1998) first identified the relationship between NAT2 acetylator status and pancreatic cancer risk, several studies had been published that describe the association between NAT2 genetic polymorphism and pancreatic cancer risk; however, none of these have provided conclusive results (Bartsch et al, 1998;Li et al, 2002Li et al, , 2006Jiao et al, 2007;Ayaz et al, 2008;Suzuki et al, 2008). To quantitatively estimate precisely the potential effects of the NAT2 acetylator phenotype on pancreatic cancer risk, we conducted a meta-analysis.…”

Section: Introductionmentioning

confidence: 99%

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Association between N-acetyltransferase 2 polymorphisms and pancreatic cancer risk: a meta-analysis

Gao

Liang

et al. 2015

Genet. Mol. Res.

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ABSTRACT. N-acetyltransferase 2 (NAT2) is an essential phase II enzyme in the metabolism of aromatic and heterocyclic amines and of hydrazines. NAT2 activity can be divided into three phenotypes: rapid, intermediate, and slow. Studies identifying an association between NAT2 polymorphism and the risk of pancreatic cancer have shown conflicting results. In order to assess this relationship comprehensively, we performed a meta-analysis that involved 1607 patients with pancreatic cancer and 1682 controls from six studies, which were selected from a group of ten, identified by a search of PubMed and Embase databases up to July 2014. Relative risks (RRs) with 95% confidence intervals (CIs) were used to evaluate the relationships. In the overall analysis, no significant associations between NAT2 rapid acetylation genotypes and pancreatic cancer risk (RR = 0.93, 95%CI = 0.73-1.19) were found; however, the results showed significant heterogeneity (I 2 = 55.0%). The results from subgroup analysis suggested that the rapid genotypes might decrease the risk of pancreatic cancer (RR = 0.56, 95%CI = 0.38-0.84) in Turkey, although the association was not significant in the United States population (RR = 0.97, 95%CI = 0.71-1.34) or in the multi-center studies (RR = 1.10, 95%CI = 0.90-1.34). Analysis of the slow acetylation genotypes demonstrated the converse outcomes.In conclusion, the results of our study suggested that the NAT2 slow acetylation genotypes might increase the susceptibility to pancreatic cancer in Europe but that these have no significant effects in the United States and multi-center populations.

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Section: Discussionmentioning

confidence: 99%

Section: Systematic Reviewmentioning

confidence: 99%

Section: Systematic Reviewmentioning

confidence: 99%

Section: Rapid Acetylation Genotypesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association between N-acetyltransferase 2 polymorphisms and pancreatic cancer risk: a meta-analysis

Gao

Liang

et al. 2015

Genet. Mol. Res.

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Functional effects of genetic polymorphisms in the N-acetyltransferase 1 coding and 3′ untranslated regions

Zhu¹,

States²,

Wang

et al. 2011

Birth Defects Research Part A: Clinical and Molecular Teratolog

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BACKGROUND The functional effects of N-acetyltransferase 1 (NAT1) polymorphisms and haplotypes are poorly understood, compromising the validity of associations reported with diseases including birth defects and numerous cancers. METHODS We investigated the effects of genetic polymorphisms within the NAT1 coding region and the 3′-untranslated region (3′-UTR) and their associated haplotypes on N- and O-acetyltransferase catalytic activities, and NAT1 mRNA and protein levels following recombinant expression in COS-1 cells. RESULTS 1088T>A (rs1057126; 3′-UTR) and 1095C>A (rs15561; 3′-UTR) each slightly reduced NAT1 catalytic activity and NAT1 mRNA and protein levels. A 9-base pair (TAATAATAA) deletion between nucleotides 1065-1090 (3′-UTR) reduced NAT1 catalytic activity and NAT1 mRNA and protein levels. In contrast, a 445G>A (rs4987076; V149I), 459G>A (rs4986990; T153T), 640T>G (rs4986783; S214A) coding region haplotype present in NAT1*11 increased NAT1 catalytic activity and NAT1 protein, but not NAT1 mRNA levels. A combination of the 9-base pair (TAATAATAA) deletion and the 445G>A, 459G>A, 640T>G coding region haplotypes, both present in NAT1*11, appeared to neutralize the opposing effects on NAT1 protein and catalytic activity, resulting in levels of NAT1 protein and catalytic activity that did not differ significantly from the NAT1*4 reference. CONCLUSIONS Since 1095C>A (3′-UTR) is the sole polymorphism present in NAT1*3, our data suggests that NAT1*3 is not functionally equivalent to the NAT1*4 reference. Furthermore, our findings provide biological support for reported associations of 1088T>A and 1095C>A polymorphisms with birth defects.

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Red meat consumption, cooking mutagens, NAT1/2 genotypes and pancreatic cancer risk in two ethnically diverse prospective cohorts

Huang

Wang

Bogumil

et al. 2021

Intl Journal of Cancer

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There is limited evidence on the association between red meat consumption and pancreatic cancer among ethnic minorities. We assessed this relationship in two large prospective cohorts: the Multiethnic Cohort Study (MEC) and the Southern Community Cohort Study (SCCS). Demographic, dietary and other risk factor data were collected at cohort entry. Red meat intake was assessed using cohort‐specific validated food frequency questionnaires. Incident pancreatic cancer cases were identified via linkages to state cancer registries. Cox regression was used to calculate relative risks (RRs) and 95% confidence intervals (CIs) for the association of red meat intake with pancreatic cancer risk in each cohort. We performed additional analyses to evaluate cooking methods, mutagens and effect modification by NAT1/2 genotypes. From a total of 184 542 (MEC) and 66 793 (SCCS) at‐risk participants, we identified 1618 (MEC) and 266 (SCCS) incident pancreatic cancer cases. Red meat consumption was associated with pancreatic cancer risk in the MEC (RRQ4vsQ1 1.18, 95% CI 1.02‐1.37) and with borderline statistical significance in the SCCS (RRQ4vsQ1 1.31, 95% CI 0.93‐1.86). This association was significant in African Americans (RRQ4vsQ1 1.49, 95% CI 1.06‐2.11) and Latinos (RRQ4vsQ1 1.44, 95% CI 1.02‐2.04) in the MEC, and among African Americans (RRQ4vsQ1 1.55, 95% CI 1.03‐2.33) in the SCCS. NAT2 genotypes appeared to modify the relationship between red meat and pancreatic cancer in the MEC (pinteraction = 0.03). Our findings suggest that the associations for red meat may be strongest in African Americans and Latinos. The mechanisms underlying the increased risk for these populations should be further investigated.

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Haplotype ofN-Acetyltransferase 1 and 2 and Risk of Pancreatic Cancer

Cited by 29 publications

References 35 publications

Association between N-acetyltransferase 2 polymorphisms and pancreatic cancer risk: a meta-analysis

Association between N-acetyltransferase 2 polymorphisms and pancreatic cancer risk: a meta-analysis

Functional effects of genetic polymorphisms in the N-acetyltransferase 1 coding and 3′ untranslated regions

Red meat consumption, cooking mutagens, NAT1/2 genotypes and pancreatic cancer risk in two ethnically diverse prospective cohorts

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