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World J Gastroenterol. Aug 28, 2026; 32(32): 117091
Published online Aug 28, 2026. doi: 10.3748/wjg.117091
Published online Aug 28, 2026. doi: 10.3748/wjg.117091
Beyond adenomatous polyposis coli: Redefining the genetic architecture of familial adenomatous polyposis through recurrent variants of uncertain significance
Si-Feng Wang, Hai-Chun Guo, Xiang-Wen Peng, Central Laboratory, Hunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control, Changsha Hospital for Maternal and Child Health Care Affiliated to Hunan Normal University, Changsha 410001, Hunan Province, China
Co-first authors: Si-Feng Wang and Hai-Chun Guo.
Author contributions: Wang SF and Guo HC contributed equally to this work and are co-first authors; Wang SF contributed to conceptualization, data curation, formal analysis, writing - original draft; Guo HC contributed to investigation, methodology, validation, visualization; Peng XW contributed to supervision, project administration, funding acquisition, writing - review and editing. All authors read and approved the final manuscript.
AI contribution statement: We used Qwen3.6 (an AI language model developed by Tongyi Lab) for language polishing and minor writing assistance. The entire conceptual framework, study design, data interpretation, results, conclusions, and overall structure of the manuscript were developed independently by the authors. No section of the main text was AI-generated. Qwen3.6 was used solely for language polishing and fluency enhancement (e.g., grammar correction, sentence restructuring for clarity, and stylistic refinement). It was also used for auxiliary literature screening and draft organization support. All scientific content, data analysis, and interpretation remain the sole responsibility of the authors. The study design, statistical analysis, result interpretation, and clinical conclusions were entirely conceived and executed by the authors. AI tools did not participate in any aspect of study design or result interpretation. All results presented are authentic and have been rigorously verified by the authors. All figures, tables, and graphical elements were designed, generated, and finalized by the authors using standard scientific software (e.g., GraphPad Prism, Python/Matplotlib, Adobe Illustrator). No AI image-generation tools were used.
Supported by Natural Science Foundation of Hunan Province, No. 2023JJ30063; Changsha Science and Technology Bureau Natural Science Surface Project, No. kq2202030; and National Natural Science Foundation of China, No. 32070817.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Xiang-Wen Peng, Associate Professor, Central Laboratory, Hunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control, Changsha Hospital for Maternal and Child Health Care Affiliated to Hunan Normal University, No. 416 East Chengnan Road, Yuhua District, Changsha 410001, Hunan Province, China.
Received: November 28, 2025
Revised: January 8, 2026
Accepted: February 5, 2026
Published online: August 28, 2026
Processing time: 246 Days and 22.9 Hours
Revised: January 8, 2026
Accepted: February 5, 2026
Published online: August 28, 2026
Processing time: 246 Days and 22.9 Hours
Core Tip
Core Tip: This commentary reinterprets a recent Hungarian cohort study on familial adenomatous polyposis (FAP) to propose a paradigm shift in our understanding of the disease. We argue that FAP is not a simple monogenic disorder but a genomic ecosystem, where the core adenomatous polyposis coli mutation is modified by a constellation of co-occurring variants, most notably in POLE and PIEZO1. We integrate recent findings on the role of POLE in generating an ultramu