Dataset Information

Prognostic Value of Drinking Status and Aldehyde Dehydrogenase 2 Polymorphism in Patients With Head and Neck Squamous Cell Carcinoma.

ABSTRACT: BACKGROUND:The association between alcohol drinking, aldehyde dehydrogenase 2 (ALDH2) polymorphism, and survival in patients with head and neck squamous cell carcinoma (HNSCC) remains unclear. METHODS:We performed a retrospective cohort study of 267 HNSCC patients at Aichi Cancer Center. Of these, 65 patients (24%) were non-drinkers, 104 (39%) were light drinkers (ethanol <46 g or <5 days/week), 46 (17%) were moderate drinkers (ethanol intake 46-68 g/day and ?5 days/week), and 52 (20%) were heavy drinkers (ethanol intake ?69 g and ?5 days/week). The prognostic value of pre-treatment drinking status and ALDH2 polymorphism was investigated using multivariate proportional hazard models. RESULTS:Drinking status was associated with disease-free survival (DFS) in HNSCC patients, with marginal statistical significance (5-year DFS: 67.9% [95% confidence interval {CI}, 53.8-78.4%] for non-drinkers, 57.6% [95% CI, 47.4-66.6%] for light drinkers, 46.1% [95% CI, 30.8-60.1%] for moderate drinkers, and 43.5% [95% CI, 29.3-56.9%] for heavy drinkers; P = 0.088). However, this association lost significance when multivariate analyses were adjusted for established prognostic factors. ALDH2 genotype was not significantly associated with DFS in HNSCC patients (5-year DFS: 85.7% [95% CI, 53.9-96.2%] for Lys/Lys, 56.2% [95% CI, 47.4-64.1%] for Glu/Lys, and 50.5% [95% CI, 40.3-59.7%] for Glu/Glu; P = 0.154). After stratification by ALDH2 genotype, we observed a significant positive dose-response relationship between drinking status and DFS in HNSCC patients with ALDH2 Glu/Glu (Ptrend = 0.029). CONCLUSIONS:In this study, we identified a significant positive dose-response relationship between pre-treatment drinking status and DFS in HNSCC patients with ALDH2 Glu/Glu. To confirm this association, further study is warranted.

SUBMITTER: Kawakita D

PROVIDER: S-EPMC4884897 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Prognostic Value of Drinking Status and Aldehyde Dehydrogenase 2 Polymorphism in Patients With Head and Neck Squamous Cell Carcinoma.

Kawakita Daisuke D Oze Isao I Hosono Satoyo S Ito Hidemi H Watanabe Miki M Yatabe Yasushi Y Hasegawa Yasuhisa Y Murakami Shingo S Tanaka Hideo H Matsuo Keitaro K

Journal of epidemiology 20160123 6

<h4>Background</h4>The association between alcohol drinking, aldehyde dehydrogenase 2 (ALDH2) polymorphism, and survival in patients with head and neck squamous cell carcinoma (HNSCC) remains unclear.<h4>Methods</h4>We performed a retrospective cohort study of 267 HNSCC patients at Aichi Cancer Center. Of these, 65 patients (24%) were non-drinkers, 104 (39%) were light drinkers (ethanol <46 g or <5 days/week), 46 (17%) were moderate drinkers (ethanol intake 46-68 g/day and ≥5 days/week), and 52 ...[more]

PMID: 26804037

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Project description:BackgroundThe CAV family, especially CAV1 and CAV2, is significantly associated with tumor development. In this study, we aimed to explore the pathogenic and prognostic roles of CAV1 and CAV2 in head and neck squamous cell carcinoma (HNSCC) through bioinformatic analysis and verified in human tissue.MethodsWe analyzed expression profiles of CAV1 and CAV2 in HNSCC and in normal tissues via data from The Cancer Genome Altas. Prognostic significance was examined by Kaplan-Meier survival curve obtained from the Xena browser together with Cox regression analysis. Co-expressed genes were uploaded to GeneMANIA and applied to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, showing interaction networks. Signaling pathways of CAV1 and CAV2 in HNSCC were analyzed by Gene Set Enrichment Analysis to elucidate potential regulatory mechanisms. Gene-drug interaction network was explored via Comparative Toxicogenomics Database. Immunohistochemistry was performed to verify theoretical results.ResultsCompared with normal tissues, expression levels of CAV1 and CAV2 were remarkably higher in HNSCC (p < 0.0001), which independently implies poor OS (CAV1: HR: 1.146, p = 0.027; CAV2: HR: 1.408, p = 0.002). Co-expressed genes (PXN, ITGA3, TES, and MET) were identified and analyzed by FunRich with CAV1 and CAV2, revealing a significant correlation with focal adhesion (p < 0.001), which has a vital influence on cancer progression. GSEA also showed cellular protein catabolic process (ES = 0.42) and proteasome complex (ES = 0.72), which is a key degradation system for proteins involved in oxidatively damaging and cell cycle and transcription, closely correlated with high expression of CAV2 in HNSCC. More importantly, we found the relationship between different immune cell infiltration degrees in the immune micro-environment in HNSCC and expression levels of CAV1/CAV2 (p < 0.0001). Gene-drug interaction network was checked via CTD. Moreover, tissue microarrays verified higher expression levels of CAV1/CAV2 in HNSCC (p < 0.0001), and the high expression subgroup indicated significantly poorer clinical outcomes (p < 0.05).ConclusionsThe results revealed that CAV1 and CAV2 are typically upregulated in HNSCC and might predict poor prognosis.

Dataset Information

Prognostic Value of Drinking Status and Aldehyde Dehydrogenase 2 Polymorphism in Patients With Head and Neck Squamous Cell Carcinoma.

Publications

Prognostic Value of Drinking Status and Aldehyde Dehydrogenase 2 Polymorphism in Patients With Head and Neck Squamous Cell Carcinoma.

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