Integrated Genomic Data Analysis for the Identification of AhR Gene Variants Associated with Cancer in the Latin American Population

Abstract

Introduction: The AhR receptor, encoded by the AhR gene, induces the activation of xenobiotic-metabolizing enzymes and is associated with the regulation of multiple signaling pathways. Polymorphic variations in AhR could potentially contribute to the development of cancer.

Objective: To describe variants in the AhR gene identified in genomic studies of cancer across different populations, with a primary focus on Latino populations.

Methods: We conducted a search for AhR variants in genomic repositories (GnomADv2.1 and The-GWAS-Catalog) as well as cancer-related databases (COSMIC, ICGC, and TCGA). We calculated the percentage of alterations in AhR by cancer type, consequence type, and population. Additionally, we performed in silico analysis of variant pathogenicity using bioinformatics tools.

Results: A total of 7,019 variants in AhR were identified, with 1,186 reported in Latino populations. GnomAD compiled 4,359 of these variants, followed by COSMIC (1,301), ICGC (1,124), TCGA (229), and GWAS (6). The primary sites with the highest number of variants were the liver (314) and breast (229), while for the Latino population, these were the skin (27) and uterus (5). The most common variants in cancer repositories were chr7:g.17389450->T and chr7:g.17375399G>C. A total of 64 high-impact variants for AhR were identified.

Conclusions: This study presents an analysis of AhR variants associated with cancer in both the general and Latino populations. The underrepresentation of Latino individuals in genomic repositories underscores the importance of detecting AhR variants in this population. Identifying risk variants in AhR enhances our understanding of the receptor's role in cancer development and progression.