Palavras-chave
Como Citar
Resumo
O câncer colorretal (CCR) é uma das neoplasias mais prevalentes no mundo, com uma etiologia multifatorial que envolve fatores genéticos e epigenéticos. No CCR hereditário, como na síndrome de Lynch, mutações em genes de reparo do DNA aumentam significativamente o risco da doença. Já no CCR esporádico, alterações epigenéticas, como a hipermetilação do promotor de genes supressores tumorais, contribuem para a instabilidade genômica e a progressão tumoral. Além da predisposição genética, fatores ambientais, como dieta, obesidade e inflamação crônica, desempenham um papel fundamental na modulação da expressão gênica e nas modificações epigenéticas associadas ao desenvolvimento da neoplasia. O rastreamento precoce, principalmente por meio da colonoscopia, é essencial para a redução da incidência e da mortalidade, especialmente em indivíduos com predisposição genética. Avanços na identificação de biomarcadores genéticos e epigenéticos possibilitam um diagnóstico mais precoce e uma abordagem terapêutica personalizada, incluindo o uso de imunoterapias e estratégias de quimioprevenção. Dessa forma, a compreensão integrada dos fatores genéticos e epigenéticos no CCR contribui para um manejo mais eficaz da doença, permitindo melhores desfechos clínicos e reduzindo seu impacto na saúde pública.
Referências
Ahadova, A., et al. The "unnatural" history of colorectal cancer in Lynch syndrome: Lessons from colonoscopy surveillance. Int J Cancer, 2021;148(4):800-11.
Bogomilova Kamburova, Z., Lubenova Popovska, S., Stefanova Kovacheva, K., Todorov Petrov, K., Enkova Nikolova, S. Familial Lynch syndrome with early age of onset and confirmed splice site mutation in MSH2: A case report. Biomed Rep, 2022;16(5):39.
Burn, J., et al. Cancer prevention with aspirin in hereditary colorectal cancer (Lynch syndrome), 10-year follow-up and registry-based 20-year data in the CAPP2 study: a double-blind, randomised, placebo-controlled trial. Lancet, 2020;395(10240):1855-63.
Cerretelli, G., et al. Molecular pathology of Lynch syndrome. J Pathol, 2020;250(5):518-31.
Chevalier, E., Benamouzig, R. Chemoprevention in hereditary digestive neoplasia: A comprehensive review. Ther Adv Gastroenterol, 2023;16:17562848231215585.
Cui, S., et al. MLH1 Exon 12 Gene Deletion Leading to Lynch Syndrome: A Case Report. Oncol Res Treat, 2021;44(7-8):414-21.
Durhuus, J. A., et al. Colorectal cancer in adolescents and young adults with Lynch syndrome: a Danish register-based study. BMJ Open, 2021;11(12).
Engel, C., et al. Associations of Pathogenic Variants in MLH1, MSH2, and MSH6 With Risk of Colorectal Adenomas and Tumors and With Somatic Mutations in Patients With Lynch Syndrome. Gastroenterology, 2020;158(5):1326-33.
Fan, A., Lu, Y. Immunotherapy in colorectal cancer: current achievements and future perspective. Int J Biol Sci, 2021;17(14):3837-49.
Gambini, D., et al. Lynch Syndrome: From Carcinogenesis to Prevention Interventions. Cancers, 2022;14(17):4102.
Kanani, A., Søreide, K. Neoadjuvant immunotherapy in primary and metastatic colorectal cancer. Br J Surg, 2021;108(12):1417-25.
Kastrinos, F., et al. Gene-Specific Variation in Colorectal Cancer Surveillance Strategies for Lynch Syndrome. Gastroenterology, 2021;161(2):453-462.e15.
Mirabdolhosseini, S. M., et al. Rare single-nucleotide variants of MLH1 and MSH2 genes in patients with Lynch syndrome. Cancer Rep (Hoboken), 2024;7(1).
Miyakura, Y., et al. Current practice of colonoscopy surveillance in patients with Lynch syndrome: A multicenter retrospective cohort study in Japan. DEN Open, 2022;3(1).
Perrod, G., et al. Colorectal cancer screening in Lynch syndrome: Indication, techniques and future perspectives. Dig Endosc, 2021;33(4):520-8.
Radulescu, S. Overview of the Genetic Aspects of Lynch Syndrome. Romanian Journal of Military Medicine, 2023;126:26-34.
Sánchez, A., et al. Quality of Colonoscopy Is Associated With Adenoma Detection and Postcolonoscopy Colorectal Cancer Prevention in Lynch Syndrome. Clin Gastroenterol Hepatol, 2022;20(3):611-621.e9.
Scott, A., et al. Saturation-scale functional evidence supports clinical variant interpretation in Lynch syndrome. Genome Biol, 2022;23(1):266.
Serrano, D., et al. Aspirin Colorectal Cancer Prevention in Lynch Syndrome: Recommendations in the Era of Precision Medicine. Genes, 2022;13(3):460.
Sievänen, T., et al. Body Weight, Physical Activity, and Risk of Cancer in Lynch Syndrome. Cancers (Basel), 2021;13(8):1849.
Silinskaite, U., et al. A Novel Mutation of MSH2 Gene in a Patient with Lynch Syndrome Presenting with Thirteen Metachronous Malignancies. J Clin Med, 2023;12(17):5502.
Soualy, A., et al. Effect of chemoprevention by low-dose aspirin of new or recurrent colorectal adenomas in patients with Lynch syndrome (AAS-Lynch): study protocol for a multicenter, double-blind, placebo-controlled randomized controlled trial. Trials, 2020;21(1):764.
Sumransub, N., Lou, E. Advances and new frontiers for immunotherapy in colorectal cancer: setting the stage for neoadjuvant success? Mol Ther Oncolytics, 2021;22:108-19.
Taniguchi, F., et al. Adequacy evaluation of the annual colonoscopic surveillance and individual difference of disease phenotypes in Lynch syndrome. Jpn J Clin Oncol, 2020;50(6):635-42.
Williams, D., et al. Somatic mismatch repair testing in evaluation of Lynch syndrome: The gap between preferred and current practices. J Genet Couns, 2020;29(5):728-36.
Zajo, K., et al. Lynch syndrome-associated colorectal cancer in a 16-year-old girl due to a de novo MSH2 mutation. BMJ Case Rep, 2020;13(7).
Este trabalho está licenciado sob uma licença Creative Commons Attribution 4.0 International License.
Copyright (c) 2025 Calina Helena Paiva de Barros Cunha, Gabriela Santos de Souza, Patricia Nunes Crispim, Luiza Carneiro Mota