Interaction between Alcohol Consumption and CYP 2C19 Gene Polymorphism in Relation to Oesophageal Squamous Cell Carcinoma

Shi, Yunying; Luo, Guo-jun; Zhang, Li; Shi, Jimin; Daoquan, Zhang; Chen, Jianmin; Chen, Xiaobo; Li, Zhuo-dong; Zhao, Qing

doi:10.1371/journal.pone.0043412

Cited by 17 publications

(10 citation statements)

References 21 publications

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“…CYP2C19*3 has a premature stop codon in exon 4 and it is biologically plausible that the CYP2C19*3 polymorphism is a modulator of cancer susceptibility; however, we did not find CYP2C19*3 to be associated with ESCC susceptibility in our study population. This finding is inconsistent with a recent report from Shi et al [ 27 ], who found that the frequency of the CYP2C19*3 A allele was significantly higher in ESCC patients than in controls (5.57% vs 1.86%, P = 0.004). Our current understanding of carcinogenesis indicates a multifactorial and multistep process involving various genetic alterations and environmental factors and it is unlikely that risk factors for cancer act in isolation from each other.…”

Section: Discussioncontrasting

confidence: 99%

Independent and combined effects of environmental factors and CYP2C19 polymorphisms on the risk of esophageal squamous cell carcinoma in Fujian Province of China

Peng

Chen²,

et al. 2015

BMC Med Genet

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BackgroundThe purpose of this study was to explore the effects of CYP2C19 gene polymorphisms and various environmental factors and their interactions on the risk of esophageal squamous cell carcinoma (ESCC) in a Chinese Han population.MethodsA 1:2 frequency-matched case control study of 285 patients and 570 controls was conducted from June 2010 to May 2011 in AnXi of Fujian province, China. Environmental factors were investigated using a self-administered questionnaire and genotypes were determined using polymerase chain reaction restriction fragment length polymorphism based methods. Unconditional logistic regression models were used for statistical evaluation.ResultsCurrent or former smoking, consumption of pickled vegetables or hot beverages/food, having a first degree relative with ESCC and history of reflux esophagitis were significantly associated with increased ESCC risk, whereas tea drinking and consumption of fresh vegetables and fruits were significantly associated with decreased risk. The CYP2C19*2 GA/AA genotype was significantly more prevalent in ESCC patients and individuals with at least one copy of the CYP2C19*2 A allele had a 3.19-fold increased risk (adjusted 95% confidence interval (CI): 2.21–4.61, P < 0.001) of ESCC compared with those without this allele. We found no significant associations between CYP2C19*3 genotypes and ESCC. The Cyp2C19*2 polymorphism appeared to have a multiplicative joint effect with tea drinking and hot beverage/food consumption (gene–tea drinking: Pinteraction = 0.042; hot beverage/food consumption: Pinteraction = 6.98 × 10−6) and an additive joint effect with pickled vegetable consumption (interaction contrast ratio = 1.96, 95% CI: 0.12–3.80).ConclusionsOur findings suggest that the CYP2C19*2 polymorphism plays an important role in the development of ESCC in the Chinese population, modified by tea drinking and consumption of pickled vegetables or hot beverages/food. Further studies are warranted to confirm our results.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-015-0156-3) contains supplementary material, which is available to authorized users.

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Section: Discussioncontrasting

confidence: 99%

Independent and combined effects of environmental factors and CYP2C19 polymorphisms on the risk of esophageal squamous cell carcinoma in Fujian Province of China

Peng

Chen²,

et al. 2015

BMC Med Genet

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“…The main study characteristics were summarized in Table 1 [20]–[36]. These studies indicate that the distribution of genotypes in controls was consistent with HWE.…”

Section: Resultsmentioning

confidence: 92%

Functional Polymorphisms in the CYP2C19 Gene Contribute to Digestive System Cancer Risk: Evidence from 11,042 Subjects

et al. 2013

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BackgroundCYP2C19 belongs to the cytochrome P450 superfamily of enzymes involved in activating and detoxifying many carcinogens and endogenous compounds, which has attracted considerable attention as a candidate gene for digestive system cancer. CYP2C19 has two main point mutation sites (CYP2C19*2, CYP2C19*3) leading to poor metabolizer (PM) phenotype. In the past decade, the relationship between CYP2C19 polymorphism and digestive system cancer has been reported in various ethnic groups; however, these studies have yielded contradictory results.MethodsTo clarify this inconsistency, we performed this meta-analysis. Databases including Pubmed, EMBASE, Web of Science and China National Knowledge Infrastructure (CNKI) were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association.ResultsIn total, 18 studies with 4,414 cases and 6,628 controls were included. Overall, significantly elevated digestive system cancer risk was associated CYP2C19 PM with OR of 1.66 (95%CI: 1.31–2.10, P<10−5) when all studies were pooled into the meta-analysis. There was strong evidence of heterogeneity (P = 0.006), which largely disappeared after stratification by cancer type. In the stratified analyses according to cancer type, ethnicity, control source and sample size, significantly increased risks were found.ConclusionsIn summary, our meta-analysis suggested that the PM phenotype caused by the variation on CYP2C19 gene is associated with increased risk of digestive system cancer, especially in East Asians.

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“…A perfect NOS score is 9. In this meta-analysis, two studies scored 9 [18,19]; four studies scored 8 [20][21][22][23]; two studies scored 7 [24,25].…”

Section: Resultsmentioning

confidence: 99%

“…In previous study, the result was inconsistent in CYP2C19*3 gene polymorphism. Wei et al found that there was no association between CYP2C19*3 gene polymorphism and ESCC risk in 2004 [22], whereas Yun et al reported that CYP2C19*3 gene A allele showed signi cantly more prevalent in ESCC patients in 2012 [19]. This meta-analysis combined the results of 6 associated studies and found that AA genotype of CYP2C19*3 polymorphism was related to ESCC risk (OR = 2.992, 95% CI = 1.122-7.981).…”

Section: Discussionmentioning

confidence: 99%

Association Between CYP2C19 Polymorphisms and Esophageal Squamous Cell Carcinoma Risk in Asian Populations: A Systematic Review and Meta-analysis

Gao

Wang

Liu

et al. 2020

Preprint

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Background: This meta-analysis was performed to evaluate the association between CYP2C19 gene polymorphisms and ESCC risk in Asian populations.Methods: A literature search was performed in main medical publication databases for the association between CYP2C19 gene polymorphisms and ESCC risk, up to May 2020. A random/fixed-effects model was used to calculate the pooled odds ratios (OR) and 95% confidence intervals (CI) to evaluate the associations, considering multiple genetic models. And people were classified into three groups according to metabolizer phenotypes: (i) extensive metabolizers (EMs: *1/*1, *1/*2, *1/*3); (ii) intermediate metabolizers (IMs: *1/*2, *1/*3) and (iii) poor metabolizers (PMs: *2/*2, *2/*3, *3/*3).Results: Eight studies with 1955 cases and 2754 controls were ultimately included that showed that individuals carrying the “A” allele of CYP2C19*2 G681A and AA genotype of CYP2C19*3 G636A were significantly associated with an increased ESCC risk (CYP2C19*2 A vs. G: OR = 1.823, 95% CI = 1.616-2.056; CYP2C19*3 AA vs. AG + GG: OR = 2.992, 95% CI = 1.122-7.981). In the analysis of metabolizer phenotypes, PMs and IMs groups were associated with ESCC risk compared to EMs (IMs vs. EMs: OR = 1.673, 95% CI = 1.281-2.186; PMs vs. EMs: OR = 2.605, 95% CI = 1.945-3.489). And PMs showed a stronger correlation (PMs vs. IMs + EMs: OR = 2.220, 95% CI = 1.705-2.891).Results: Eight studies with 1955 cases and 2754 controls were ultimately included that showed that individuals carrying the “A” allele of CYP2C19*2 G861A and AA genotype of CYP2C19*3 G636A were significantly associated with an increased ESCC risk (CYP2C19*2 A vs. G: OR = 1.823, 95% CI = 1.616-2.056; CYP2C19*3 AA vs. AG + GG: OR = 2.992, 95% CI = 1.122-7.981). In the analysis of metabolizer phenotypes, PMs and IMs groups were associated with ESCC risk compared to EMs (IMs vs. EMs: OR = 1.673, 95% CI = 1.281-2.186; PMs vs. EMs: OR = 2.605, 95% CI = 1.945-3.489). And PMs showed a stronger correlation (PMs vs. IMs + EMs: OR = 2.220, 95% CI = 1.705-2.891).Conclusions: Our meta-analysis revealed that “A” allele (AA+AG) ofCYP2C19*2 and AA genotype of CYP2C19*3 polymorphism are significantly associated with ESCC risk. In metabolizer phenotypes, PMs and IMs are associated with an increased risk of ESCC in Asian populations.

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Interaction between Alcohol Consumption and CYP 2C19 Gene Polymorphism in Relation to Oesophageal Squamous Cell Carcinoma

Cited by 17 publications

References 21 publications

Independent and combined effects of environmental factors and CYP2C19 polymorphisms on the risk of esophageal squamous cell carcinoma in Fujian Province of China

Independent and combined effects of environmental factors and CYP2C19 polymorphisms on the risk of esophageal squamous cell carcinoma in Fujian Province of China

Functional Polymorphisms in the CYP2C19 Gene Contribute to Digestive System Cancer Risk: Evidence from 11,042 Subjects

Association Between CYP2C19 Polymorphisms and Esophageal Squamous Cell Carcinoma Risk in Asian Populations: A Systematic Review and Meta-analysis

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