Dataset Information

Clinical significance of ALDH2 rs671 polymorphism in esophageal cancer: evidence from 31 case-control studies.

ABSTRACT:

Background

Aldehyde dehydrogenase 2 (ALDH2), a critical enzyme for the detoxification of alcohol, is associated with many types of cancers. To verify the relationship of ALDH2 rs671 G>A polymorphism and esophageal cancer (EC), we performed a meta-analysis of a total of 31 published data including 8,510 patients and 16,197 controls.

Methods

The pooled odds ratio (OR) and the 95% confidence interval (CI) were calculated using a fixed or random-effects model. Heterogeneity (PH ), publication bias, and sensitivity analysis were also determined.

Results

Although a protective effort was found in the rs671 homozygote comparison (AA/GG: OR=0.69; 95% CI=0.48-0.98), the heterozygote comparison was apparently associated with the risk of EC, particularly in the Chinese population (

Ag/gg

OR=1.39; 95% CI=1.03-1.87). Alcohol consumption remarkably increased this risk, especially in the AG genotype. Drinking men with the AG genotype appeared to show a higher risk (

Ag/gg

OR=4.39; 95% CI=1.24-6.55) than drinking women.

Conclusion

The present meta-analysis provided advanced information regarding the association of the ALDH2 A>G polymorphism and EC. Taken together, insights from this study suggested an enhanced effect on the development of EC through a genetic-environmental interaction.

SUBMITTER: Zhao T

PROVIDER: S-EPMC4376259 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

Clinical significance of ALDH2 rs671 polymorphism in esophageal cancer: evidence from 31 case-control studies.

Zhao Tingting T Wang Chun C Shen Lili L Gu Dongying D Xu Zhi Z Zhang Xunlei X Xu Yong Y Chen Jinfei J

OncoTargets and therapy 20150323

<h4>Background</h4>Aldehyde dehydrogenase 2 (ALDH2), a critical enzyme for the detoxification of alcohol, is associated with many types of cancers. To verify the relationship of ALDH2 rs671 G>A polymorphism and esophageal cancer (EC), we performed a meta-analysis of a total of 31 published data including 8,510 patients and 16,197 controls.<h4>Methods</h4>The pooled odds ratio (OR) and the 95% confidence interval (CI) were calculated using a fixed or random-effects model. Heterogeneity (PH ), pub ...[more]

PMID: 25848305

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Project description:BackgroundMicroRNAs (miRNAs) are a family of endogenous, small and non-coding RNAs that regulate gene expression negatively at the post-transcriptional level by suppressing translation or degrading target mRNAs, and are involved in diverse biological and pathological processes. Single nucleotide polymorphisms (SNPs) which are located in the miRNA-coding genes may participate in the process of development and diseases by altering the expression of mature miRNA. Recent studies investigating the association between hsa-mir-499 polymorphism (rs3746444) and cancer risk have yielded conflicting results.MethodsIn this meta-analysis, we conducted a search of case-control studies on the associations of SNP rs3746444 with susceptibility to cancer in electronic databases. A total of 31 studies involving 12799 cases and 14507 controls were retrieved and the strength of the association was estimated by pooled odds ratios (ORs) and 95% confidence intervals (CIs). Hardy-Weinberg equilibrium (HWE) was assessed by the goodness-of-fit chi-square test in controls. Subgroup analyses were done by racial descent and cancer type. Publication bias of literatures was evaluated by visual inspection of funnel plots and the linear regression asymmetry test by Egger et al. Sensitivity analysis was conducted by excluding one study at a time to examine the influence of individual data set on the pooled ORs.ResultsOverall, significant association between rs3746444 polymorphism and susceptibility to cancer was identified in TC versus TT and TC/CC versus TT (dominant) models. In the stratified analyses, increased risks were found in Asians, but not in Caucasians in all comparison models tested. Moreover, significant association with an increased risk was found in Chinese population. Also, much higher significant association with increased cancer risks were found in Iranian population. In different cancer types, a decreased risk was found in esophageal cancer.ConclusionOur meta-analysis suggested that hsa-mir-499 rs3746444 T > C polymorphism is associated with the risk of cancer in Asians, mainly in Iranian and Chinese population. However, rs3746444 T > C polymorphism is negatively associated with the risk of esophageal cancer.

Project description:BackgroundAldehyde dehydrogenase 2 (ALDH2) plays an important role in the endogenous aldehyde detoxification of various types of cells. ALDH2*2, a variant allele of the ALDH2 polymorphism rs671, leads to decreased enzymatic activity. ALDH2*2 may enhance tumor antigen presentation due to aldehyde-induced DNA damage while suppressing peripheral blood T cell counts and T cell activation.MethodsOn the basis of our hypothesis that rs671 affects the sensitivity of immune checkpoint inhibitors (ICIs), we evaluated the effects of rs671 on patients with thoracic malignancies who started ICI therapy in 2016-2019. The cohort consisted of 105 cases, including 64 cases with adenocarcinoma and 30 cases with squamous cell carcinoma, 49 of whom were ALDH2*2 carriers. The first ICI was PD-1/PD-L1 inhibitor (Nivolumab, Pembrolizumab, or Atezolizumab) in all cases.ResultsThe best response to anti-PD-1/PD-L1 therapy (partial response/stable disease/progressive disease) was 36%/50%/14% in the rs671(-) cases; however, the response was relatively poor in the rs671(+) cases (27%/29%/45%, respectively) (p = 0.002). The hazard ratio (95% confidence interval) of disease progression within the observation period of 6 months for the rs671(+) cases was estimated to be 5.0 (2.5-10) after the adjustment for covariates, including sex, Brinkman index, treatment line, tumor tissue programmed death-ligand 1 positivity rate, tumor tissue EGFR mutation. This association was also maintained in a stratified analysis, suggesting that ALDH2*2 is an independent negative predictive factor for the short-term prognosis of anti-PD-1/PD-L1 therapy. Thus, the progression-free survival (PFS) ratio of the rs671(+) cases decreased rapidly after ICI initiation but was eventually higher than that of the rs671(-) cases (restricted mean survival time in 12 months from 2 to 3 years afterward was 1.3 times that of the rs671(-) cases). Moreover, the highest PFS ratio after 2 years among sub-groups was found in the first-line treatment sub-group of rs671(+) group (40%).ConclusionsOur study suggests that rs671 may be an accurate and cost-effective predictor of PD-1/PD-L1 inhibitor treatment, in which optimal case selection is an important issue.

Dataset Information

Clinical significance of ALDH2 rs671 polymorphism in esophageal cancer: evidence from 31 case-control studies.

Background

Methods

Results

Ag/gg

Ag/gg

Conclusion

Publications

Clinical significance of ALDH2 rs671 polymorphism in esophageal cancer: evidence from 31 case-control studies.

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