{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Recent studies have implicated "}, {"type": "b", "children": [{"type": "t", "text": "COLCA2"}]}, {"type": "t", "text": " (also known as C11orf93) as a functionally relevant gene at chromosome 11q23.1 that may influence colorectal cancer (CRC) risk. Genetic association analyses have shown that risk‐related variants—particularly rs3802842 and other linked single‐nucleotide polymorphisms—correlate with altered COLCA2 expression in both normal and tumor colonic tissues, and with changes in local lymphocyte density and inflammatory pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n COLCA2 protein is expressed in the cytoplasm of epithelial, immune, and other cell types, suggesting that it may operate at the interface between epithelial cell function and immune regulation in the colon. Such dual localization supports a role for COLCA2 in modulating both tumor cell behavior and the local immune microenvironment during colon tumorigenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Functional assays indicate that regulatory elements—including enhancers and bidirectional promoters—in this genetic locus are modulated by risk variants and epigenetic mechanisms like DNA methylation. These regulatory effects ultimately alter COLCA2 expression levels, further linking it to CRC susceptibility."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}, {"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, studies of microRNA function have identified COLCA2 as a potential target of miR‑375, implicating it in the control of cell proliferation and suggesting a role in tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings support a model in which COLCA2 acts as a mediator linking inherited genetic variation to pathways of immune modulation and epithelial cell regulation in colorectal cancer, with possible broader implications for other inflammatory or immune‐mediated conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}, {"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": "\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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