The “JSCCR Guidelines for the Clinical Practice of Hereditary Colorectal Cancer” was published in 2012 and have been revised every four years since then, with the 2024 edition published this time. In this article, we list the main revisions of the guidelines for familial adenomatous polyposis (FAP): 1) In recent years, multiple genes causing adenomatous polyposis of the colon have been identified. In light of this, we have added the terms “FAP”, “APC-related polyposis”, “adenomatous polyposis”, etc., as well as diseases and conditions that require differentiation, and have mentioned the need for genetic testing in view of future advances in multigene panel testing. 2) A reliable treatment that can avoid cancer death due to colorectal cancer is prophylactic proctocolectomy, but since insurance now covers Intensive Downstaging Polypectomy (IDP) for sparse type FAP patients who do not wish to undergo surgery, this article details this treatment method. 3) A new classification proposed in Japan for desmoid tumors associated with FAP was introduced, and new agents were also mentioned. 4) Five issues that are controversial in the development of the FAP practice algorithm are addressed as CQs. We hope that the updated guideline will be useful for appropriate diagnosis and treatment of patients.

　The 2024 version of the Hereditary Colorectal Cancer Clinical Practice Guidelines introduces significant updates in the management of Lynch syndrome. It presents cumulative incidence rates of associated tumors by causative genes (MLH1, MSH2 & EPCAM, MSH6, PMS2) and expands the tumor spectrum beyond colorectal and endometrial cancer to include ovarian, urinary tract, bladder, gastric, small bowel, pancreatic, bile duct, and brain tumors. 　In terms of diagnosis, the revised guidelines incorporate companion diagnostics and comprehensive genomic profiling as additional pathways to identify suspected Lynch syndrome cases, alongside the Amsterdam criteria and universal screening. The BRAFV600E test, now covered by insurance, has also been newly included in the diagnostic process. 　For surveillance, the guidelines now recommend gene-specific strategies for colorectal cancer. Additionally, they establish separate recommendations for uterine and ovarian cancer to reflect their distinct risk profiles. A new surveillance protocol for pancreatic cancer has also been introduced. 　The revision also updates the Clinical Questions section, expanding it to include universal screening for Lynch syndrome, surveillance protocols, chemoprevention strategies, risk-reducing surgery, and Helicobacter pylori screening. These updates are expected to contribute to improving the detection, risk assessment, and management of Lynch syndrome, ultimately enhancing patient outcomes.

　In the case of hereditary colorectal cancer, there are two types of diagnoses: one confirmed by genetic testing and the other by clinical criteria. Genetic testing can be used to confirm the presence or absence of a cancer predisposition syndrome in an individual. It can also aid in appropriate follow-up observation and management of the individual, as well as in appropriate diagnosis and medical management of unaffected relatives. 　In the 2006 revision of medical fees in Japan, microsatellite instability testing was included in the insurance system. It has been used as a screening test for Lynch syndrome, which is one type of hereditary colorectal cancer. In recent years, it has been expanded to include applications for testing aimed at selecting drug therapy. While genetic testing for hereditary colorectal cancer is not covered by health insurance in Japan, an increasing number of testing companies now offer multigene panel testing (MGPT) for cancer predisposition syndromes, in addition to genetic testing for specific hereditary colorectal cancers. Research has shown that there are patients who have a cancer predisposition syndrome but cannot be diagnosed using conventional genetic testing, including MGPT. It is necessary to be aware of issues such as false negatives and variants of unknown significance.

　Familial adenomatous polyposis (FAP) is characterized by numerous colorectal adenomas, inevitably leading to colorectal cancer. Prophylactic colectomy is effective but associated with reduced QOL and developing desmoid tumor risk. Intensive Downstaging Polypectomy (IDP), actively resecting polyps, has emerged as a promising alternative due to advancements in endoscopic techniques. 　IDP aims to avoid colectomy and is now covered by the Japanese healthcare insurance system. The multi-center J-FAPP Study III demonstrated that IDP avoided colectomy in over 90％ of cases after 5 years. Also, our single-center prospective study in FAP patients with multiple non-ampullary duodenal polyps demonstrated the safety and efficacy of IDP using cold snare polypectomy. Most patients achieved a downstaging of the Spigelman classification after 1 year without major adverse events. 　IDP is a promising, minimally invasive approach to improving QOL for FAP patients. Future research should focus on combining IDP with chemoprevention to reduce the treatment burden further and enhance the outcome of the patients with FAP.

Cancer chemoprevention is a cancer prevention method using chemical compounds, such as drugs, and is mainly targeted a high-risk group of cancer. Hereditary colorectal cancer includes familial adenomatous polyposis and Lynch syndrome. However, there is no standard drug therapy option aiming colorectal cancer prevention for them, i.e. it remains at the research level. Our research group is trying to develop the first cancer prevention drug in Japan. This article mainly overviewed clinical trials of colorectal cancer prevention using aspirin.

Since its inclusion in Japanese insurance coverage in 2019, the importance of cancer gene panel testing has increased in the field of head and neck cancer. It is also possible to incidentally find pathogenic variants of genes unrelated to the diagnostic purpose when performing cancer gene panel testing (hereinafter referred to as “secondary findings”). Therefore, it is necessary to understand how to manage these secondary findings. We experienced a case where we performed cancer gene panel testing on a patient with adenoid cystic carcinoma of the oropharynx who had a history of breast cancer and confirmed a pathogenic variant of the BRCA1 gene as a secondary finding. We referred the patient to a hereditary tumor clinic, where a detailed family history was taken. The BRCA1 pathogenic variant was disclosed to the patient, providing valuable information for treatment options at the time of the second primary breast cancer and beneficial information for relatives. We report this valuable case here.

The patient has been diagnosed with quadruple cancer, including metachronous multiple colon cancer and metachronous bilateral breast cancer. She underwent surgery for right breast cancer at age 65, left breast cancer and ascending colon cancer at age 76, and transverse colon cancer at age 81. Cancer related family history included that her father passed at age60 from gastric cancer, her mother dying at age 72 from colon cancer, eldest daughter diagnosed with colon cancer at age 58, younger sister dying at age 37 from gastric cancer, niece (daughter of the deceased sister) diagnosed with breast cancer at age 37, and second younger sister diagnosed with colon cancer at age 56 and breast cancer at age 61. Lynch syndrome was initially suspected due to the strong family history of colon cancer. However, BRAF mutation (-), MSI testing (-), and immunohistochemical staining (IHC) for mismatch repair proteins in the transverse colon cancer tissue all showed no loss of expression, ruling out Lynch syndrome. Subsequently, we focused on the frequent occurrence of breast cancer and conducted BRCA genetic testing. A pathogenic mutation, c.188T>A (p.Leu63*), was detected in BRCA1, resulting in a diagnosis of hereditary breast and ovarian cancer syndrome (HBOC). IHC for BRCA1 protein was conducted on the two colon cancers and two breast cancers, confirming their association with BRCA1 mutations. This report describes a case of overlapping HBOC involving metachronous bilateral breast cancer and metachronous multiple colon cancer with a strong family history of colon cancer.