Expressive

rs116203444 (ADH4): Aerodigestive Cancer Risk Locus

Key takeaways

  • rs116203444 is located within ADH4, part of the alcohol dehydrogenase gene cluster at chromosome 4q23.
  • The 4q23 ADH gene region has been linked to pleiotropic risk across lung, oral/pharyngeal, laryngeal, and esophageal squamous cell cancers in a meta-analysis of nearly 76,000 individuals.
  • The published study at this locus specifically names ADH1B, not ADH4 or rs116203444 directly, so the evidence for this exact variant is indirect.
  • Evidence is preliminary; effect sizes specific to rs116203444 are not reported in the available literature.

Key takeaways

  • rs116203444 is located within ADH4, part of the alcohol dehydrogenase gene cluster at chromosome 4q23.
  • The 4q23 ADH gene region has been linked to pleiotropic risk across lung, oral/pharyngeal, laryngeal, and esophageal squamous cell cancers in a meta-analysis of nearly 76,000 individuals.
  • The published study at this locus specifically names ADH1B, not ADH4 or rs116203444 directly, so the evidence for this exact variant is indirect.
  • Evidence is preliminary; effect sizes specific to rs116203444 are not reported in the available literature.

What the research says A genome-wide association meta-analysis of aerodigestive squamous cell carcinomas (SqCCs) - cancers of the lung, oral cavity and pharynx, larynx, and esophagus - combined data from 13,887 cases and 61,961 controls of European ancestry. The 4q23 chromosomal region, which contains the alcohol dehydrogenase gene cluster (including ADH1B and the nearby ADH4), was identified as a previously described risk locus that shows pleiotropic (cross-cancer) association signals spanning multiple SqCC types. The study named ADH1B as the indexed gene at this locus and did not specifically report rs116203444 or ADH4 as lead variants.

Reported associations

  • Aerodigestive squamous cell carcinoma (pleiotropy at 4q23): The 4q23 region containing alcohol dehydrogenase genes was found to show cross-cancer associations spanning lung (7,426 cases), oral/pharyngeal (5,452 cases), laryngeal (693 cases), and esophageal (316 cases) SqCC in a meta-analysis of European-ancestry populations; no specific effect size for ADH4 or this variant was reported.

Evidence quality Only one study was available for this review. The meta-analysis pooled four SqCC cancer types with 13,887 cases and 61,961 controls of European ancestry using fixed-effects and subset-based (ASSET) meta-analytic methods. The 4q23 locus is described in the study as a previously identified risk region, with its pleiotropic nature across SqCC sites confirmed here; the indexed gene named is ADH1B, not ADH4 or rs116203444 specifically. No independent replication data are described in the available text. Because this variant is not individually named in the study, the evidence linking rs116203444 to aerodigestive cancer risk is indirect and preliminary, and no effect estimate for this variant is available from the provided data.

Lifestyle considerations No lifestyle considerations on file for this variant.

Lifestyle context

Concrete actions anchored to the cited research. We do not prescribe, we describe.

Screening

  • Aerodigestive cancer screening Moderate

    Carriers of C allele at rs116203444 show increased genetic risk for aerodigestive squamous cell cancer in GWAS analysis

    Discuss with physician regarding enhanced screening protocols; consider periodic endoscopic surveillance based on individual risk assessment

Frequently asked questions

What does the ADH4 gene do?

ADH4 encodes alcohol dehydrogenase 4, an enzyme involved in breaking down alcohol in the body. It belongs to a cluster of related genes at chromosome 4q23 that includes ADH1B and other alcohol dehydrogenase family members.

Is rs116203444 linked to cancer risk?

The chromosomal region containing ADH4 (4q23) has been associated with aerodigestive squamous cell cancers in a large GWAS meta-analysis. However, the study specifically named the nearby gene ADH1B at this locus, and no effect size for rs116203444 itself was reported.

What cancers are linked to the 4q23 ADH gene region?

Research has linked the 4q23 region to lung, oral/pharyngeal, laryngeal, and esophageal squamous cell carcinomas. The association appears pleiotropic, meaning variants in this region may influence risk across more than one cancer type at once.

How strong is the evidence for rs116203444?

Evidence is preliminary and indirect. Only one study was available for review, it did not specifically name rs116203444 or ADH4 as the lead variant at 4q23, and no replication data are described in the available literature.