Relationship of ALDH2 rs671 and CYP2E1 rs2031920 with hepatocellular carcinoma susceptibility in East Asians: a meta-analysis

Chen, Junhong; Pan, Weicong; Chen, Yongjin; Wen, Lijia; Tu, Jihao

doi:10.1186/s12957-020-1796-0

Cited by 7 publications

(16 citation statements)

References 30 publications

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“…A meta-analysis conducted by Chen et al . 77 found that the ALDH2 rs671 polymorphism is not associated with HCC susceptibility in East Asians, and this is similar to the conclusion from Liu et al . 35 Interestingly, Huang et al .…”

Section: Related Liver Diseasessupporting

confidence: 89%

“…75 Recently, a study involving both mice and human patients showed that ALDH2 gene deficiency correlates well with a higher risk for advancement of alcohol related-fibrosis to HCC. 76 A meta-analysis conducted by Chen et al 77 found that the ALDH2 rs671 polymorphism is not associated with HCC susceptibility in East Asians, and this is similar to the conclusion from Liu et al 35 Interestingly, Huang et al 78 found that the ALDH2 polymorphisms had a certain impact on resolution of HCC in patients. The result showed that HCC patients with a defective allele of ALDH2 have a promising postoperative outcome, after Kaplan-Meier analysis and univariate followed by multivariate Cox proportional hazard analysis indicated that the GG genotype is an independent clinical predictor for shorter time-to-distant metastasis (adjusted p=0.019) and shorter overall survival (adjusted p=0.001).…”

Section: Hepatocellular Carcinomasupporting

confidence: 54%

“…25 Meanwhile, HCC cases are increasing rapidly in China, 69 which accounts for approximately 90% of all cases of primary liver cancer. 72 Therefore, scientists have been endeavoring to explore the relationship between ALDH2 gene mutation and HCC (Table 2 35,[73][74][75][76][77][78][79] ).…”

Section: Hepatocellular Carcinomamentioning

confidence: 99%

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Role of ALDH2 in Hepatic Disorders: Gene Polymorphism and Disease Pathogenesis

Wang¹,

Chang²,

Li³

et al. 2021

Journal of Clinical and Translational Hepatology

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Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme of alcohol metabolism and it is involved in the cellular mechanism of alcohol liver disease. ALDH2 gene mutations exist in about 8% of the world’s population, with the incidence reaching 45% in East Asia. The mutations will result in impairment of enzyme activity and accumulation of acetaldehyde, facilitating the progression of other liver diseases, including non-alcoholic fatty liver diseases, viral hepatitis and hepatocellular carcinoma, through adduct formation and inflammatory responses. In this review, we seek to summarize recent research progress on the correlation between ALDH2 gene polymorphism and multiple liver diseases, with an attempt to provide clues for better understanding of the disease mechanism and for strategy making.

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Section: Related Liver Diseasessupporting

confidence: 89%

Section: Hepatocellular Carcinomasupporting

confidence: 54%

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Role of ALDH2 in Hepatic Disorders: Gene Polymorphism and Disease Pathogenesis

Wang¹,

Chang²,

Li³

et al. 2021

Journal of Clinical and Translational Hepatology

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“…A prognostic model involved apoptosis-related genes with impressive prognostic predictive power was also established in HCC [ 31 ]. Furthermore, numerous prognostic genes and prognostic signature for HCC have been reported by many studies [ 32 – 35 ] and further evaluated by some meta-analysis [ 36 , 37 ]. However, the relationship between pyroptosis and HCC is not fully understood.…”

Section: Discussionmentioning

confidence: 99%

A pyroptosis-related gene signature predicts prognosis and immune microenvironment in hepatocellular carcinoma

Jin

Ping

et al. 2022

World J Surg Onc

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Background Hepatocellular carcinoma (HCC) is a highly malignant tumor with a very poor prognosis. Pyroptosis is an inflammatory form of cell death and plays an important role in cancer development. The prognostic value of pyroptosis-related genes (PRGs) in HCC has not been studied extensively. Methods Unsupervised consensus clustering analysis was performed to identify two subtypes based on the expression profiles of prognostic PRGs in the The Cancer Genome Atlas (TCGA) database, and the differences between the two subtypes were compared. A prognostic model based on four PRGs was established by further least absolute shrinkage and selection operator (LASSO) Cox regression analysis and multivariate Cox regression analysis. Results Two subtypes (clusters 1 and 2) were identified by consensus clustering based on prognostic PRGs in HCC. Survival outcomes, biological function, genomic alterations, immune cell infiltration, and immune checkpoint genes were compared between the subtypes. Cluster 2 had a worse survival outcome than cluster 1. Cluster 2 was enriched for hallmarks of cancer progression, TP53 mutation, tumor-promoting immune cells, and immune checkpoint genes, which may contribute to the poor prognosis. A prognostic risk signature that predicted the overall survival (OS) of patients was constructed and validated. Consequently, a risk score was calculated for each patient. Combined with the clinical characteristics, the risk score was found to be an independent prognostic factor for survival of HCC patients. Further analysis revealed that the risk score was closely associated with the levels of immune cell infiltration and the expression profiles of immune checkpoint genes. Conclusions Collectively, our study established a prognostic risk signature for HCC and revealed a significant correlation between pyroptosis and the HCC immune microenvironment.

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“…10,12,14,33 For other cancers sites, existing genotypic evidence has been inconclusive. 15,16,19,22,[34][35][36][37][38] A previous meta-analysis of case-control studies found no clear associations of ALDH2-rs671 with cancers in the liver (1522 cases, 7 studies), colon-rectum (2356 cases, 10 studies), stomach (5558 cases, 8 studies) or lung (1105 cases, 2 studies). 15 In contrast, recent large case-control studies (>1000 cases each) in South Korea and Japan showed that ALDH2-rs671 AA and AG genotypes were associated with 22% to 30% lower risk of colorectal cancer, 16 but approximately 23% to 30% higher risk of stomach cancer, 19,38 compared to GG genotype.…”

Section: Discussionmentioning

confidence: 99%

Alcohol metabolism genes and risks of site‐specific cancers in Chinese adults: An 11‐year prospective study

Yang

Kartsonaki

et al. 2022

Intl Journal of Cancer

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Two genetic variants that alter alcohol metabolism, ALDH2-rs671 and ADH1B-rs1229984, can modify oesophageal cancer risk associated with alcohol consumption in East Asians, but their associations with other cancers remain uncertain. ALDH2-rs671 G>A and ADH1B-rs1229984 G>A were genotyped in 150 722 adults, enrolled from 10 areas in China during 2004 to 2008. After 11 years' follow-up, 9339 individuals developed cancer. Cox regression was used to estimate hazard ratios (HRs) for site-specific cancers associated with these genotypes, and their potential interactions with alcohol consumption. Overall, the A-allele frequency was 0.21 for ALDH2-rs671 and 0.69 for ADH1B-rs1229984, with A-alleles strongly associated with lower alcohol consumption. Among men, ALDH2-rs671 AA genotype was associated with HR of 0.69 (95% confidence interval: 0.53-0.90) for IARC alcohol-related cancers (n = 1900), compared to GG genotype. For ADH1B-rs1229984, the HRs of AG and AA vs GG genotype were 0.80 (0.69-0.93) and 0.75 (0.64-0.87) for IARC alcoholrelated cancers, 0.61 (0.39-0.96) and 0.61 (0.39-0.94) for head and neck cancer (n = 196) and 0.68 (0.53-0.88) and 0.60 (0.46-0.78) for oesophageal cancer (n = 546). There were no significant associations of these genotypes with risks of liver (n = 651), colorectal (n = 556), stomach (n = 725) or lung (n = 1135) cancers.Among male drinkers, the risks associated with higher alcohol consumption were greater among ALDH2-rs671 AG than GG carriers for head and neck, oesophageal and lung cancers (P interaction < .02). Among women, only 2% drank alcohol regularly, with no comparable associations observed between genotype and cancer.

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Relationship of ALDH2 rs671 and CYP2E1 rs2031920 with hepatocellular carcinoma susceptibility in East Asians: a meta-analysis

Cited by 7 publications

References 30 publications

Role of ALDH2 in Hepatic Disorders: Gene Polymorphism and Disease Pathogenesis

Role of ALDH2 in Hepatic Disorders: Gene Polymorphism and Disease Pathogenesis

A pyroptosis-related gene signature predicts prognosis and immune microenvironment in hepatocellular carcinoma

Alcohol metabolism genes and risks of site‐specific cancers in Chinese adults: An 11‐year prospective study

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