Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe, Saitama, 350-8550, Japan.
The Committee of Hereditary Colorectal Cancer, Japanese Society for Cancer of the Colon and Rectum, Tokyo, Japan.
Int J Clin Oncol. 2023 Dec;28(12):1641-1650. doi: 10.1007/s10147-023-02419-6. Epub 2023 Oct 18.
Colorectal polyp burden is crucial for the management of patients with familial adenomatous polyposis (FAP). However, accurate evaluation of polyp burden is difficult to standardize. This study aimed to examine the possible utility of genotype-oriented management of colorectal neoplasms in patients with FAP.
Clinicopathological data from genetically proven patients with FAP was analyzed using the database of a nationwide retrospective Japanese multicenter study. The cumulative incidence of CRC was evaluated between different genotype groups. Genotype-1 were defined as germline variants on attenuated FAP-associated regions (codons 1-177, alternative splice site of exon 10 (codon 312), 1581-2843) and Genotype-2 as the other variants. Weibull and Joinpoint analyses were performed to determine the annual percentage changes in CRC risk.
Overall, 69 men and 102 women were included. Forty-eight patients underwent colorectal resection for the first CRC, and five patients underwent resection for first cancer in the remnant anorectal segment after prophylactic surgery. The 70-year cumulative incidence of CRC in all patients was 59.3%. Patients with Genotype-1 (n = 23) demonstrated a lower risk of CRC stages II-IV than those with Genotype-2 (n = 148, P = 0.04). The risk of stage II-IV CRC was estimated to increase markedly at the age of 49 years in the Genotype-1 patients and 34 years in the Genotype-2 patients, respectively.
Different interventional strategies based on genotypes may be proposed for the clinical management of patients with FAP. This policy needs to be validated in further prospective studies focusing on long-term endoscopic intervention and optimal age at prophylactic (procto)colectomy.
结直肠息肉负担对于家族性腺瘤性息肉病（FAP）患者的管理至关重要。然而，准确评估息肉负担难以标准化。本研究旨在探讨基于基因型的结直肠肿瘤管理在 FAP 患者中的可能应用。
利用全国性回顾性日本多中心研究的数据库分析经基因证实的 FAP 患者的临床病理数据。评估不同基因型组之间 CRC 的累积发生率。基因型 1 定义为腺瘤相关区域（密码子 1-177、外显子 10 的替代剪接位点（密码子 312）、1581-2843）的种系变异，基因型 2 为其他变异。采用威布尔和 Joinpoint 分析确定 CRC 风险的年百分比变化。
共有 69 名男性和 102 名女性患者入组。48 名患者因首次 CRC 行结直肠切除术，5 名患者因预防性手术后残留直肠肛门段首次癌症行切除术。所有患者 70 年 CRC 累积发生率为 59.3%。基因型 1（n=23）患者 CRC Ⅱ-Ⅳ期的风险低于基因型 2（n=148，P=0.04）。基因型 1 患者的Ⅱ-Ⅳ期 CRC 风险估计在 49 岁时显著增加，基因型 2 患者在 34 岁时显著增加。
基于基因型的不同干预策略可能被提出用于 FAP 患者的临床管理。该策略需要在进一步的前瞻性研究中进行验证，重点关注长期内镜干预和预防性（直肠）结肠切除术的最佳年龄。
