{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Recent studies have identified the 11q23.1 locus as a critical region in colorectal cancer (CRC) susceptibility, with two co‐regulated genes—COLCA1 and COLCA2—emerging as promising candidates driving disease pathogenesis. In normal and tumor colon tissues, COLCA1 shows genotype‐dependent expression; for example, transcripts correlate with risk alleles such as rs3802842 and localize to crystalloid granules within immune cell types (eosinophils, mast cells, neutrophils, macrophages, and dendritic cells), thereby implicating COLCA1 in immunomodulatory and inflammatory pathways relevant to CRC development."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond CRC, altered COLCA1 expression has been linked with patient survival outcomes in breast cancer, and it has been incorporated into prognostic risk signatures in lung adenocarcinoma, suggesting that its role as a biomarker may extend across several malignancies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In autoimmune liver disease such as primary biliary cholangitis, increased COLCA1 (along with COLCA2) expression has been observed in association with functional risk variants, further supporting a role in immune‐mediated pathologies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n COLCA1 is also differentially expressed in early-stage colon adenocarcinoma and is included among key genes influenced by risk single-nucleotide polymorphisms, underscoring its involvement in disease initiation and progression as well as its potential impact on patient prognosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, epigenetic studies have revealed that alcohol-related changes in DNA methylation at CpG sites mapping to the COLCA1/COLCA2 locus may further elevate CRC risk, emphasizing the interplay between genetic variants, epigenetic modifications, and environmental exposures in modulating COLCA1 expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Overall, these findings highlight the multifaceted role of COLCA1 in immune response regulation and cancer-related pathways. Its genotype-dependent expression and association with both genetic risk variants and epigenetic alterations suggest that COLCA1 may contribute to tumorigenesis and serve as a valuable prognostic biomarker not only in colorectal cancer but also in other malignancies.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Vanya D Peltekova, Mathieu Lemire, Aamer M Qazi, et al. 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