Predictive modeling for the germline pathogenic variant of the APC gene in patients with adenomatous polyposis: proposing a new APC score

Misato Takao; Tatsuro Yamaguchi; Hidetaka Eguchi; Okihide Suzuki; Yoshiko Mori; Noriyasu Chika; Takeshi Yamada; Yasushi Okazaki; Naohiro Tomita; Tadashi Nomizu; Tomoyuki Momma; Tetsuji Takayama; Kohji Tanakaya; Kiwamu Akagi; Noriko Tanabe; Hideyuki Ishida

doi:10.1007/s00595-024-02894-y

Predictive modeling for the germline pathogenic variant of the APC gene in patients with adenomatous polyposis: proposing a new APC score

Surg Today. 2024 Jul 6. doi: 10.1007/s00595-024-02894-y. Online ahead of print.

Authors

Misato Takao¹, Tatsuro Yamaguchi^{2

3}, Hidetaka Eguchi⁴, Okihide Suzuki⁵, Yoshiko Mori⁵, Noriyasu Chika⁵, Takeshi Yamada⁶, Yasushi Okazaki⁴, Naohiro Tomita⁷, Tadashi Nomizu⁸, Tomoyuki Momma⁹, Tetsuji Takayama¹⁰, Kohji Tanakaya¹¹, Kiwamu Akagi¹², Noriko Tanabe¹³, Hideyuki Ishida⁵

Affiliations

¹ Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
² Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Saitama, Japan. [email protected].
³ Department of Clinical Genetics, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-Ku, Tokyo, 113-8677, Japan. [email protected].
⁴ Diagnostics and Therapeutics of Intractable Diseases and Intractable Disease Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan.
⁵ Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
⁶ Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan.
⁷ Division of Lower GI Surgery, Department of Surgery, Hyogo College of Medicine, Hyogo, Japan.
⁸ Department of Surgery, Hoshi General Hospital, Fukushima, Japan.
⁹ Department of Gastrointestinal Tract Surgery, Fukushima Medical University, Fukushima, Japan.
¹⁰ Department of Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
¹¹ Department of Surgery, NHO Iwakuni Clinical Center, Yamaguchi, Japan.
¹² Division of Molecular Diagnosis and Cancer Prevention, Saitama Cancer Center, Saitama, Japan.
¹³ Department of Genomic Medicine, Saitama Medical Center, Saitama Medical University, Saitama, Japan.

PMID: 38970662
DOI: 10.1007/s00595-024-02894-y

Abstract

Background: The precise diagnosis and medical management of patients with suspected familial adenomatous polyposis should be based on genetic testing, which may not always be available. Therefore, establishing a new model for predicting the likelihood of a germline pathogenic variant (GPV) of APC based on its clinical manifestations could prove to be useful in clinical practice.

Methods: The presence of GPVs of APC gene was investigated in 162 patients with adenomatous polyposis (≥ 10 polyps) using a multigene panel or single-gene testing. To generate a predictive model for GPV of the APC gene, a logistic regression analysis was performed using the clinicopathological variables available at the time of the diagnosis of adenomatous polyposis.

Results: Ninety (55.6%) patients had GPV of the APC gene. According to a multivariate logistic regression analysis, age < 40 years, polyps ≥ 100, fundic gland polyposis, and a family history of colorectal polyposis were found to be independent predictors of the GPV of APC and were used to establish a formula for predicting the GPV of APC using the four predictors. The prediction model had an area under the curve of 0.91 (0.86-0.96) according to a receiver operating characteristic analysis.

Conclusion: The model for predicting the GPV of APC will help patients with adenomatous polyposis and physicians make decisions about genetic testing.

Keywords: APC score; Familial adenomatous polyposis; Genetic testing; Polyposis.