Published online Oct 14, 2026. doi: 10.3748/wjg.120596
Revised: April 18, 2026
Accepted: June 9, 2026
Published online: October 14, 2026
Processing time: 186 Days and 23.4 Hours
In some patients with familial adenomatous polyposis (FAP) who lack pathogenic variants in the coding region of the adenomatous polyposis coli (APC) gene, ab
To determine the genotype-phenotype correlations of APC promoter-region ab
A systematic review of the PubMed database was conducted to identify and summarize evidence on promoter-associated FAP and GAPPS published between January 1993 and December 2025. The reference lists of eligible articles were screened to identify additional relevant studies. Altogether, 35 eligible studies, primarily comprising case reports and case series, were included. These studies were categorized according to the variant type and associated clinical phenotype.
The APC promoter-region abnormalities were classified into four categories. Class I consists of promoter 1B-limited deletions and is predominantly associated with an attenuated FAP phenotype, characterized by colorectal polyposis and cancer. Class II comprises variants affecting the Yin Yang 1 binding site and is subclassified into II-a (GAPPS phenotype), II-b (classical FAP), and II-c (mixed phenotypes), despite affecting a narrow genomic region. Class III includes point variants outside the Yin Yang 1 binding site, with one family exhibiting an attenuated FAP phenotype. Class IV comprises large structural alterations involving the entire promoter region and has been associated with the attenuated or classical FAP phenotype. The available evidence was limited and primarily derived from small case series.
Recognizing genotype-phenotype relationships improves understanding of APC promoter-associated diseases and may inform their clinical management. However, further studies are needed to refine these findings.
Core Tip: Abnormalities in the adenomatous polyposis coli promoter region are among the causes of familial adenomatous polyposis in patients without pathogenic variants in the coding region, as well as gastric adenocarcinoma and proximal polyposis of the stomach. In the present systematic review, the adenomatous polyposis coli promoter-region abnormalities were classified as follows: Deletions limited to promoter 1B; variants affecting the Yin Yang 1 (YY1) binding site; point variants outside the YY1 binding site; and large deletions or structural alterations encompassing the entire promoter-region. The variants affecting the YY1 binding site were further subclassified according to clinical phenotype.