Dataset Information

Alcohol Consumption, ALDH2 Polymorphism as Risk Factors for Upper Aerodigestive Tract Cancer Progression and Prognosis.

ABSTRACT: The upper aerodigestive tract (UADT) is highly susceptible to multiple primary cancers originated from squamous epithelia and constitutes a field of cancerization. Patients with head and neck cancer (head and neck squamous cell carcinoma, HNSCC) are at high risk of developing multiple cancers in the esophagus (esophageal squamous cell carcinoma, ESCC). Conversely, esophageal cancer patients are prone to develop multiple primary tumors in the head and neck region. The East Asian-specific dysfunctional ALDH2*2 missense mutation is a genetic risk factor for UADT cancer. It is not only associated with increased incidences of UADT cancer, but is also implicated in faster cancer progression and poorer prognosis. Alcohol use is a major lifestyle risk factor which causes UADT cancer among ALDH2*2 carriers. The accumulation of the immediate metabolite of alcohol, acetaldehyde, is likely the genotoxic agents that is involved in the process of tumorigenesis. This review summarizes recent publications on the risk and association of ALDH2*2 mutation, alcohol consumption in synchronous, metachronous UADT cancer. Possible molecular mechanisms involved in cancer initiation, progress and prognosis are discussed. The review also highlights a need for precision medicine-based preventive and therapeutic strategies by integrating lifestyle and genetic risk factors, such as alcohol consumption, genotypes of the alcohol metabolizing genes, ADH1B and ALDH2, into a risk assessment model for better screening, surveillance and treatment outcome.

SUBMITTER: Chen CH

PROVIDER: S-EPMC8956056 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Alcohol Consumption, <i>ALDH2</i> Polymorphism as Risk Factors for Upper Aerodigestive Tract Cancer Progression and Prognosis.

Chen Che-Hong CH Wang Wen-Lun WL Hsu Ming-Hung MH Mochly-Rosen Daria D

Life (Basel, Switzerland) 20220227 3

The upper aerodigestive tract (UADT) is highly susceptible to multiple primary cancers originated from squamous epithelia and constitutes a field of cancerization. Patients with head and neck cancer (head and neck squamous cell carcinoma, HNSCC) are at high risk of developing multiple cancers in the esophagus (esophageal squamous cell carcinoma, ESCC). Conversely, esophageal cancer patients are prone to develop multiple primary tumors in the head and neck region. The East Asian-specific dysfunct ...[more]

PMID: 35330099

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Project description:PurposeSeveral publications have investigated the association between the Cyclin D1 G to A substitution at nucleotide 870 (CCND1 G870A) polymorphism and squamous cell carcinoma (SCC) of the upper aerodigestive tract (UADT), but their conclusions still remain controversial. We conducted a meta-analysis to precisely evaluate this association.Patients and methodsWe electronically searched the Chinese National Knowledge Infrastructure, PubMed, and Embase (up to January 2015) databases for case-control studies on the association between the CCND1 G870A polymorphism and SCC of the UADT, and 23 studies were included in total.ResultsThe meta-analysis results showed that there was a significant association between the CCND1 G870A polymorphism and the risk of SCC of the UADT (AA vs GG: odds ratio [OR] =1.33, 95% confidence interval [CI] =1.01-1.74, P<0.001 for heterogeneity; GA/AA vs GG: OR =1.24, 95% CI =1.01-1.51, P<0.001 for heterogeneity; AA vsGa/ggOR =1.16, 95% CI =0.97-1.39, P<0.001 for heterogeneity; allele A vs allele G: OR =1.14, 95% CI =1.00-1.30, P<0.001 for heterogeneity; GA vs GG: OR =1.18, 95% CI =0.98-1.42, P<0.001 for heterogeneity). However, when analyzing prognosis, allele G was a potential risk factor for poor tumor differentiation (AA vsGa/ggOR =2.60, 95% CI =1.15-5.86, P=0.836 for heterogeneity) and reduced disease-free intervals (OR =2.08, 95% CI =1.17-3.69, P=0.134 for heterogeneity). In the subgroup analysis, the cancer susceptibility of Asian groups, population-based control groups, nasopharyngeal cancer groups, and esophageal SCC groups were more likely to be affected by the CCND1 G870A polymorphism. No significant publication bias was found in our analysis (P=0.961 for Egger's test and P=0.245 for Begg's test).ConclusionThe results of the present meta-analysis suggest that the variant CCND1 870A allele might confer an elevated risk of SCC of the UADT, particularly among Asians and individuals who have esophageal or nasopharyngeal cancers. Moreover, the CCND1 870A allele might also confer better tumor differentiation grades and longer disease-free intervals.

Project description:Alcohol use is a leading risk factor for the global disease burden including liver diseases. However, the combined effect of alcohol use and body mass index (BMI) on alcohol-related diseases has seldom been examined. We examined whether alcohol consumption and BMI could act together to increase mortality from nonneoplastic liver diseases, upper aero-digestive tract (UADT) cancers, and alcohol use disorders (AUD) in middle-aged Korean men.107,735 men (mean age, 58.8 years) participated in a postal survey in 2004 and were followed until 2010, by linkage to national death records. Hazard ratios (HRs) of cause-specific death were calculated after adjustment for confounders.Each 5-drink (approximately 45 g alcohol) higher weekly alcohol consumption was associated with increased mortality, by approximately 70% for nonneoplastic liver disease mortality (HR = 1.70, P < 0.001), approximately 60% for UADT cancer mortality (HR = 1.64, P < 0.001), and approximately 70% for AUD mortality (HR = 1.71, P < 0.001). Generally, BMI was inversely associated with these alcohol-related diseases (HR per each 5 kg/m higher BMI = 0.18-0.46, P < 0.001 for each cause), while, in participants with BMI ≥25 kg/m, each 5 kg/m higher BMI was also associated with an elevated mortality from nonneoplastic liver diseases of approximately 150% (HR = 2.52, P = 0.001). Men with BMI < 21 kg/m and weekly alcohol consumption ≥14 drinks showed markedly higher mortality from nonneoplastic liver diseases (HR = 5.7), alcoholic liver diseases (HR = 9.3), UADT cancers (HR = 10.5), and esophageal cancer (HR = 15.5), compared to men drinking less than 1 drink/wk with BMI ≥25 kg/m. The combined effect of low BMI and high weekly alcohol consumption was 2.25- to 3.29-fold greater than the additive effect of each factor for these alcohol-related diseases (P < 0.05 for each cause).Alcohol consumption and low BMI were related to deaths from nonneoplastic liver diseases, UADT cancers, and AUD, with evidence of a supra-additive combined effect of both factors. High BMI was also related to deaths from nonneoplastic liver diseases. Men with a low BMI (<23 kg/m) are suggested to be prone to the harmful effects of alcohol.

Dataset Information

Alcohol Consumption, ALDH2 Polymorphism as Risk Factors for Upper Aerodigestive Tract Cancer Progression and Prognosis.

Publications

Alcohol Consumption, <i>ALDH2</i> Polymorphism as Risk Factors for Upper Aerodigestive Tract Cancer Progression and Prognosis.

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