Effect of genetic profiling on surgical decisions at hereditary colorectal cancer syndromes
Yasaman Goudarzi,
Khaterehsadat Monirvaghefi,
Salar Aghaei,
Seyed Siamak Amiri,
Mahdi Rezaei,
Atefeh Dehghanitafti,
Ali Azarpey,
Alireza Azani,
SeyedAbbas Pakmehr,
Hamid Reza Eftekhari,
Safa Tahmasebi,
Shahriar Zohourian Shahzadi,
Mansour Rajabivahid
Affiliations
Yasaman Goudarzi
Department of Medical Science, Shahroud Branch, Islamic Azad University, Iran
Khaterehsadat Monirvaghefi
Department of Adult Hematology & Oncology, School of Medicine, Ayatollah Khansari Hospital, Arak University of Medical Sciences, Arak, Iran
Salar Aghaei
Faculty of Medicine, Medical University of Kurdistan, Sanandaj, Iran
Seyed Siamak Amiri
Department of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran
Mahdi Rezaei
Clinical Research Department, Pasteur Institute of Iran, Tehran, Iran
Atefeh Dehghanitafti
Department of General Surgery, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran
Ali Azarpey
Emory University School of Medicine, Atlanta, GA, USA
Alireza Azani
Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran; Corresponding author. Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
SeyedAbbas Pakmehr
School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
Hamid Reza Eftekhari
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Safa Tahmasebi
Student Research Committee, Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Shahriar Zohourian Shahzadi
Erfan Hospital, Iran University of Medical Sciences, Tehran, Iran; Corresponding author. Erfan Hospital, Iran University of Medical Sciences.
Mansour Rajabivahid
Department of Internal Medicine, Valiasr Hospital, Zanjan University of Medical Sciences, Zanjan, Iran; Corresponding author.
Hereditary colorectal cancer syndromes, such as Lynch syndrome and familial adenomatous polyposis (FAP), present significant clinical challenges due to the heightened cancer risks associated with these genetic conditions. This review explores genetic profiling impact on surgical decisions for hereditary colorectal cancer (HCRC), assessing options, timing, and outcomes. Genotypes of different HCRCs are discussed, revealing a connection between genetic profiles, disease severity, and outcomes. For Lynch syndrome, mutations in the MLH1, MSH2, MSH6, and PMS2 genes guide the choice of surgery. Subtotal colectomy is recommended for patients with mutations in MLH1 and MSH2, while segmental colectomy is preferred for those with MSH6 and PMS2 mutations. In cases of metachronous colon cancer after segmental colectomy, subtotal colectomy with ileorectal anastomosis is advised for all mutations. Surgical strategies for primary rectal cancer include anterior resection or abdominoperineal resection (APR), irrespective of the specific mutation. For rectal cancer occurring after a previous segmental colectomy, proctocolectomy with ileal pouch-anal anastomosis (IPAA) or APR with a permanent ileostomy is recommended. In FAP, surgical decisions are based on genotype-phenotype correlations. The risk of desmoid tumors post-surgery supports a single-stage approach, particularly for certain APC gene variants. Juvenile Polyposis Syndrome (JPS) surgical decisions involve genetic testing, polyp characteristics with attention to vascular lesions in SMAD4 mutation carriers. However, genetic profiling does not directly dictate the specific surgical approach for JPS. In conclusion this review highlights the critical role of personalized surgical plans based on genetic profiles to optimize patient outcomes and reduce cancer risk. Further research is needed to refine these strategies and enhance clinical guidelines.
