Impact of alcohol dehydrogenase 3 (ADH3 or ADH1C) genetic variation on head and neck cancer susceptibility: A systematic review, meta-analysis, functional analysis, and trial sequential analysis.

Objectives: Alcohol drinking is a major risk factor for head and neck cancer (HNC), and this risk may be modified by alcohol dehydrogenase (ADH) genes. The first systematic review and meta-analysis was designed with more studies and added trial sequential analysis and functional analysis for a better understanding of the role of ADH3 polymorphism in HNC patients.
Methods: A search was performed across several databases, including PubMed/Medline, Web of Science, Scopus, and Cochrane Library, up to May 5, 2024, without any restrictions to find pertinent studies. The RevMan 5.3 software was used to calculate the effect sizes. These were expressed as the odds ratio (OR) with a 95 % confidence interval.
Results: Twenty-seven articles were included in the meta-analysis. The frequency of *1/*1, *1/*2, and *2/*2 genotypes in cases with HNC was 47.14 %, 41.06 %, and 11.80 %, respectively, and in controls was 50.56 %, 38.29 %, and 11.15 %, respectively. The pooled OR for the allelic model is 1.11 (p = 0.18), for the homozygous model is 0.95 (p = 0.64), for the heterozygous model is 0.99 (p = 0.90), for the dominant model is 1.11 (p = 0.14), and for the recessive model is 0.98 (p = 0.78). In the Asians, the three models showed an increased significant association. In the cancer subtype subgroup, a protective significant association was found in the pharyngeal cancer subtype.
Conclusions: The current analysis suggests that ADH3 polymorphism may not have a significant impact on the risk of HNC, but the polymorphism had an increased risk in Asians and a protective role in pharyngeal cancers.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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