Novel Non-invasive Strategies Using Genetic Biomarkers for Early Detection of Colorectal Cancer
DOI:
https://doi.org/10.47611/jsrhs.v13i4.8038Keywords:
Colorectal Cancer, Genetic mutations, DNA methylation, Genetic biomarkers, Early detection, Non-invasive testing methodAbstract
Among individuals aged between 20 years and 49 years, colorectal cancer (CRC) is one of the leading causes of death. This is partly due to the fact that CRC is not diagnosed earlier because symptoms do not showcase until later stages— a hallmark of CRC. The gold standard testing for CRC continues to be the colonoscopy, a test that discourages patients because of its invasive nature. In light of this problem, this research paper methodically reviews previously published papers and current/ongoing studies to explore a testing process for CRC that uses genetic biomarkers (mutated APC, KRAS, and TP53 genes and methylated DNA) in the stool samples. The genetic markers chosen were based on the major genes involved in the colorectal carcinogenesis pathway. Testing these genetic biomarkers in combination has shown promise by increasing sensitivity and efficiency of CRC screening by using technologies, including next generation sequencing, polymerase chain reaction (PCR) and methylation-specific PCR. Such non-invasive testing methods can encourage patient compliance and help combat the growing death rate. In the future, utilizing genetic biomarkers should become more widespread, increasing CRC diagnosis rates. Additionally, individuals should continue to pay attention to unusual symptoms, reach out to medical professionals, and take a more proactive stance in their health. The end of this paper explores several ongoing or completed clinical trials that use various types of biomarkers (which are not limited to genetic biomarkers), showcasing the urgency of this issue.
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Allison, J. E., Fraser, C. G., Halloran, S. P., & Young, G. P. (2014). Population Screening for Colorectal Cancer Means Getting FIT: The Past, Present, and Future of Colorectal Cancer Screening Using the Fecal Immunochemical Test for Hemoglobin (FIT). Gut and Liver, 8(2), 117–130. https://doi.org/10.5009/gnl.2014.8.2.117
American Cancer Society. (2020). What Is Colorectal Cancer? | How Does Colorectal Cancer Start? Www.cancer.org; American Cancer Society. https://www.cancer.org/cancer/types/colon-rectal-cancer/about/what-is-colorectal-cancer.html
Armaghany, T., Wilson, J. D., Chu, Q., & Mills, G. (2012). Genetic alterations in colorectal cancer. Gastrointestinal Cancer Research : GCR, 5(1), 19–27. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3348713/
Barnell, E. K., Land, J., Kruse, K., Scott, M. C., Wedeking, B., Morrison, C., Grass, C., Zuniga, A., Wurtzler, E. M., & Duncavage, E. J. (2024). Analytical Validation of the Multitarget Stool RNA Test for Colorectal Cancer Screening. Journal of Molecular Diagnostics, 26(8). https://doi.org/10.1016/j.jmoldx.2024.05.001
Beniwal, S. S., Lamo, P., Kaushik, A., Dionisio Lorenzo Lorenzo-Villegas, Liu, Y., & ArunSundar MohanaSundaram. (2023). Current Status and Emerging Trends in Colorectal Cancer Screening and Diagnostics. Biosensors, 13(10), 926–926. https://doi.org/10.3390/bios13100926
Berger, B. M., Levin, B., & Hilsden, R. J. (2016). Multitarget stool DNA for colorectal cancer screening: A review and commentary on the United States Preventive Services Draft Guidelines. World Journal of Gastrointestinal Oncology, 8(5), 450. https://doi.org/10.4251/wjgo.v8.i5.450
Centers for Disease Control and Prevention. (2024). Symptoms of Colorectal Cancer. Colorectal Cancer. https://www.cdc.gov/colorectal-cancer/symptoms/index.html
Chen, C., Deng, L., Wei, S., Gowda, N., Gu, H., Chiorean, E. G., Mohammad Abu Zaid, Harrison, M. L., Pekny, J. F., Loehrer, P. J., Zhang, D., Zhang, M., & Raftery, D. (2015). Exploring Metabolic Profile Differences between Colorectal Polyp Patients and Controls Using Seemingly Unrelated Regression. Journal of Proteome Research, 14(6), 2492–2499. https://doi.org/10.1021/acs.jproteome.5b00059
Cheng, Y.-C., Wu, P.-H., Chen, Y.-J., Yang, C.-H., Huang, J.-L., Chou, Y.-C., Chang, P.-K., Wen, C.-C., Jao, S.-W., Huang, H.-H., Tsai, Y.-H., & Pai, T.-W. (2021). Using Comorbidity Pattern Analysis to Detect Reliable Methylated Genes in Colorectal Cancer Verified by Stool DNA Test. Genes, 12(10), 1539. https://doi.org/10.3390/genes12101539
Chung, S. S., Ali, S. I., & Cash, B. D. (2022). The Present and Future of Colorectal Cancer Screening. Gastroenterology & Hepatology, 18(11), 646–653. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9972668/
Church, T. R., Wandell, M., Lofton-Day, C., Mongin, S. J., Burger, M., Payne, S. R., Castaños-Vélez, E., Blumenstein, B. A., Rösch, T., Osborn, N., Snover, D., Day, R. W., & Ransohoff, D. F. (2013). Prospective evaluation of methylatedSEPT9in plasma for detection of asymptomatic colorectal cancer. Gut, 63(2), 317–325. https://doi.org/10.1136/gutjnl-2012-304149
Dienstmann, R. (2019). Molecular Classification of Colon Cancer: New Insights. [Video] Youtube. https://youtu.be/on6tUOTgayM?si=hURlHq-bj-aOkby8
Divjak, M. (2020). The Role of KRas in Cancer. [Video] Youtube. https://youtu.be/pD5q4TlZW-M?si=Tk7nGSbxraOL6pZH
Eguchi, S., Kohara, N., Komuta, K., & Kanematsu, T. (1996). Mutations of the p53 gene in the stool of patients with resectable colorectal cancer. Cancer, 77(8), 1707–1710. https://doi.org/10.1002/(sici)1097-0142(19960415)77:8%3C1707::aid-cncr43%3E3.0.co;2-0
Fatemi, N., Sascha Tierling, Hamidreza Aboulkheyr Es, Varkiani, M., Ehsan Nazemalhosseini Mojarad, Hamid Asadzadeh Aghdaei, Walter, J., & Mehdi Totonchi. (2022). DNA methylation biomarkers in colorectal cancer: Clinical applications for precision medicine. International Journal of Cancer, 151(12), 2068–2081. https://doi.org/10.1002/ijc.34186
Galm, O., & Herman, J. G. (2005). Methylation-specific polymerase chain reaction. Methods in Molecular Medicine, 113, 279–291. https://doi.org/10.1385/1-59259-916-8:279
Gao, X., Liu, H., Yu, J., & Nie, Y. (2024). DNA methylation biomarkers for early detection of gastric and colorectal cancers. Cancer Biology and Medicine, 20(12), 955–962. https://doi.org/10.20892/j.issn.2095-3941.2023.0443
Godman, H. (2024). New approaches to colorectal cancer screening - Harvard Health. Harvard Health; Harvard Health. https://www.health.harvard.edu/staying-healthy/new-approaches-to-colorectal-cancer-screening
Guan, Y.-F., Li, G.-R., Wang, R.-J., Yi, Y.-T., Yang, L., Jiang, D., Zhang, X.-P., & Peng, Y. (2012). Application of next-generation sequencing in clinical oncology to advance personalized treatment of cancer. Chinese Journal of Cancer, 31(10), 463–470. https://doi.org/10.5732/cjc.012.10216
Gude, S. S., Veeravalli, R. S., Vejandla, B., Gude, S. S., Venigalla, T., & Chintagumpala, V. (2023). Colorectal Cancer Diagnostic Methods: The Present and Future. Cureus, 15(4). https://doi.org/10.7759/cureus.37622
Han, Y. D., Oh, T. J., Chung, T.-H., Jang, H. W., Kim, Y. N., An, S., & Kim, N. K. (2019). Early detection of colorectal cancer based on presence of methylated syndecan-2 (SDC2) in stool DNA. Clinical Epigenetics, 11(1). https://doi.org/10.1186/s13148-019-0642-0
He, S.-Y., Li, Y.-C., Wang, Y., Peng, H.-L., Zhou, C.-L., Zhang, C.-M., Chen, S.-L., Yin, J.-F., & Lin, M. (2022). Fecal gene detection based on next generation sequencing for colorectal cancer diagnosis. World Journal of Gastroenterology, 28(25), 2920–2936. https://doi.org/10.3748/wjg.v28.i25.2920
Jančík, S., Drábek, J., Radzioch, D., & Hajdúch, M. (2010). Clinical Relevance of KRAS in Human Cancers. Journal of Biomedicine and Biotechnology, 2010, 1–13. https://doi.org/10.1155/2010/150960
Liebl, M. C., & Hofmann, T. G. (2021). The Role of p53 Signaling in Colorectal Cancer. Cancers, 13(9). https://doi.org/10.3390/cancers13092125
Lin, J., Zhang, L., Chen, M., Chen, J., Wu, Y., Wang, T., Lu, Y., Ba, Z., Cheng, X., Xu, R., Tian, T., Sun, A., Zhang, T., & Chen, M. (2022). Evaluation of combined detection of multigene mutation and SDC2/SFRP2 methylation in stool specimens for colorectal cancer early diagnosis. International Journal of Colorectal Disease, 37(6), 1231–1238. https://doi.org/10.1007/s00384-022-04170-2
Liu, C., Xu, L., Li, W., Jie, M., Xue, W., & Yu, W. (2021). Multiple Biomarker-Combined Screening for Colorectal Cancer Based on Bisulfate Conversion-Free Detection of Fecal DNA Methylation. BioMed Research International, 2021, 1–10. https://doi.org/10.1155/2021/1479748
Lowery, J. T., Ahnen, D. J., Schroy, P. C., Hampel, H., Baxter, N., Boland, C. R., Burt, R. W., Butterly, L., Doerr, M., Doroshenk, M., Feero, W. G., Henrikson, N., Ladabaum, U., Lieberman, D., McFarland, E. G., Peterson, S. K., Raymond, M., Samadder, N. J., Syngal, S., & Weber, T. K. (2016). Understanding the contribution of family history to colorectal cancer risk and its clinical implications: A state-of-the-science review. Cancer, 122(17), 2633–2645. https://doi.org/10.1002/cncr.30080
Mayo Clinic. (2023). Capsule endoscopy - Mayo Clinic. Mayoclinic.org. https://www.mayoclinic.org/tests-procedures/capsule-endoscopy/about/pac-20393366
MedlinePlus. (2024). SEPTIN9 gene: MedlinePlus Genetics. Medlineplus.gov. https://medlineplus.gov/genetics/gene/septin9/
National Cancer Institute. (n.d.). Types of Colorectal Cancer | SEER Training. Training.seer.cancer.gov. https://training.seer.cancer.gov/colorectal/intro/types.html
National Cancer Institute. (2019). Evaluation of Stool Based Markers for the Early Detection of Colorectal Cancers and Adenomas Great Lakes New England (GLNE) Clinical Validation Center. Early Detection Research Network. https://edrn.nci.nih.gov/data-and-resources/protocols/456-evaluation-of-stool-based-markers-for-the-early-detection-of-colorectal-cancers-and-adenomas-great-lakes-new-england-glne-clinical-validation-center/
National Cancer Institute. (2021). Tests to Detect Colorectal Cancer and Polyps. National Cancer Institute; Cancer.gov. https://www.cancer.gov/types/colorectal/screening-fact-sheet
NCI Staff. (2020). Colorectal Cancer Rising among Young Adults - National Cancer Institute. Www.cancer.gov. https://www.cancer.gov/news-events/cancer-currents-blog/2020/colorectal-cancer-rising-younger-adults
Nguyen, L. H., Goel, A., & Chung, D. C. (2020). Pathways of Colorectal Carcinogenesis. Gastroenterology, 158(2), 291–302. https://doi.org/10.1053/j.gastro.2019.08.059
Olmedillas-López, S., Dennis César Lévano-Linares, Laura, C., Vega-Clemente, L., Edurne León Sánchez, Villagrasa, A., Ruíz-Tovar, J., García-Arranz, M., & Damián García-Olmo. (2017). Detection of KRAS G12D in colorectal cancer stool by droplet digital PCR. World Journal of Gastroenterology, 23(39), 7087–7097. https://doi.org/10.3748/wjg.v23.i39.7087
Phillips, T. (2008). The Role of Methylation in Gene Expression | Learn Science at Scitable. Nature.com. https://www.nature.com/scitable/topicpage/the-role-of-methylation-in-gene-expression-1070/
Pickhardt, P. J. (2012). Missed lesions at CT colonography: lessons learned. Abdominal Imaging, 38(1), 82–97. https://doi.org/10.1007/s00261-012-9897-z
Rahib, L., Wehner, M. R., Matrisian, L. M., & Nead, K. T. (2021). Estimated Projection of US Cancer Incidence and Death to 2040. JAMA Network Open, 4(4), e214708. https://doi.org/10.1001/jamanetworkopen.2021.4708
Shankar, V. (2016). The Guardian of the Genome. Functions, regulation, and inactivation [Video]. Youtube. https://youtu.be/8Mp7D7qWxG4?si=TStlNJ2gBMuPuaBt
Shankar, V. (2022). Colorectal carcinoma: Epidemiology, Risk Factors & Pathogenesis [Video]. Youtube. https://youtu.be/9JHFvhPxtUI?si=Jk2eaMh8fTCJYwKK
Shapiro, J. A., Bobo, J. K., Church, T. R., Rex, D. K., Chovnick, G., Thompson, T. D., Zauber, A. G., Lieberman, D., Levin, T. R., Joseph, D. A., & Nadel, M. R. (2017). A Comparison of Fecal Immunochemical and High-Sensitivity Guaiac Tests for Colorectal Cancer Screening. The American Journal of Gastroenterology, 112(11), 1728–1735. https://doi.org/10.1038/ajg.2017.285
Sobhani, I., Bergsten, E., Couffin, S., Amiot, A., Nebbad, B., Barau, C., de’Angelis, N., Rabot, S., Canoui-Poitrine, F., Mestivier, D., Pédron, T., Khazaie, K., & Sansonetti, P. J. (2019). Colorectal cancer-associated microbiota contributes to oncogenic epigenetic signatures. Proceedings of the National Academy of Sciences, 116(48), 24285–24295. https://doi.org/10.1073/pnas.1912129116
Sullivan, K., & Lewis, R. (2023). More younger people are being diagnosed with advanced colon cancer. It’s not clear why. NBC News. https://www.nbcnews.com/health/cancer/colon-cancer-advanced-younger-symptoms-rcna72983
Taylor, D. P., Burt, R. W., Williams, M. S., Haug, P. J., & Cannon–Albright, L. A. (2010). Population-Based Family History–Specific Risks for Colorectal Cancer: A Constellation Approach. Gastroenterology, 138(3), 877–885. https://doi.org/10.1053/j.gastro.2009.11.044
The Cancer Genome Atlas Network. (2012). Comprehensive molecular characterization of human colon and rectal cancer. Nature, 487(7407), 330–337. https://doi.org/10.1038/nature11252
ThermoFisher. (2020). What is qPCR? Ask a Scientist. https://www.thermofisher.com/blog/ask-a-scientist/what-is-qpcr/
Traverso, G., Shuber, A., Levin, B., Johnson, C., Olsson, L., Schoetz, D. J., Hamilton, S. R., Boynton, K., Kinzler, K. W., & Vogelstein, B. (2002). Detection ofAPCMutations in Fecal DNA from Patients with Colorectal Tumors. New England Journal of Medicine, 346(5), 311–320. https://doi.org/10.1056/nejmoa012294
Vernia, F., Valvano, M., Fabiani, S., Stefanelli, G., Longo, S., Viscido, A., & Latella, G. (2021). Are Volatile Organic Compounds Accurate Markers in the Assessment of Colorectal Cancer and Inflammatory Bowel Diseases? A Review. Cancers, 13(10), 2361. https://doi.org/10.3390/cancers13102361
Woodfield, G., Ilaria Belluomo, Laponogov, I., Kirill Veselkov, Cross, A. J., Hanna, G. B., Boshier, P. R., Lin, G., Antonis Myridakis, Ayrton, O., Patrik Španěl, Vidal-Diez, A., Romano, A., Martin, J., Marelli, L., Groves, C., Monahan, K., Christos Kontovounisios, & Saunders, B. P. (2022). Diagnostic Performance of a Noninvasive Breath Test for Colorectal Cancer: COBRA1 Study. Gastroenterology, 163(5), 1447-1449.e8. https://doi.org/10.1053/j.gastro.2022.06.084
World Health Organization. (2023). Colorectal cancer. Who.int; World Health Organization: WHO. https://www.who.int/news-room/fact-sheets/detail/colorectal-cancer?gad_source=1&gclid=CjwKCAjw1920BhA3EiwAJT3lSZkqSEozwawRIckNN8_Ac0o8ivwaSBVX-UOu4I0bN5IQsD5jybC7zBoCG5UQAvD_BwE
Zhu, J., Djukovic, D., Deng, L., Gu, H., Himmati, F., Abu Zaid, M., Chiorean, E. G., & Raftery, D. (2015). Targeted serum metabolite profiling and sequential metabolite ratio analysis for colorectal cancer progression monitoring. Analytical and Bioanalytical Chemistry, 407(26), 7857–7863. https://doi.org/10.1007/s00216-015-8984-8
Zhu, J., Djukovic, D., Deng, L., Gu, H., Himmati, F., Chiorean, E. G., & Raftery, D. (2014). Colorectal Cancer Detection Using Targeted Serum Metabolic Profiling. Journal of Proteome Research, 13(9), 4120–4130. https://doi.org/10.1021/pr500494u
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