Introduction: Colorectal cancer is the third most common cancer in Morocco. The profile of patients according to RAS status has been the subject of few studies in Morocco. The objective of our study is to evaluate the epidemiological, anatomopathological and molecular parameters of a Moroccan population according to RAS status and to search for a possible correlation between the latter and the RAS mutation. Material and Methods: This is a cross-sectional study conducted at the Mohamed VI Center for Cancer Treatment in Casablanca during the period from May 2015 to February 2021. Included were 282 patients with histologically confirmed colorectal cancer whose RAS status was known and significant. The main criteria studied were age, gender, personal and family history of colorectal cancer or other types of cancers, anatomo-pathological characteristics (tumor site, histological type, tumor size, lymph node invasion, laterality, differentiation grade, stage, BRAF, MSI…), therapeutic modalities and evolutionary data. Results: 47.2% of patients were RAS Wild Type and 52.8% of whom were RAS mutated with a predominance of KRAS mutation (92.6%). The analysis of the association between the RAS mutation and the epidemiological and anatomopathological characteristics of the patients did not reveal any statistically significant correlation, except for two parameters: age (p = 0.035) and degree of differentiation (p < 0.003). Thus, mutated RAS status was associated with advanced age and good differentiation of colorectal adenocarcinomas. The evolution of the patients under treatment as well as their prognosis did not show any statistically significant difference between the two wild-type and mutated RAS groups. Conclusion: The latter was not correlated with the anatomopathological and epidemiological characteristics of the patients except for the advanced age and the well-differentiated type of colorectal adenocarcinoma.
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Kaikai, I. A. , Belhouari, M. , Mchanter, H. , Bourhafour, M. , Chekrine, T. , Bouchbika, Z. , Benchakroun, N. , Jouhadi, H. , Sahraoui, S. , Regragui, M. , Benayad, S. , Karkouri, M. , Bendahhou, K. and Tawfiq, N. (2023). Colorectal Cancer in Morocco: Is There a Correlation between the Epidemiological and Anatomopathological Profile and the RAS Status?. Open Access Library Journal, 10, e050. doi: http://dx.doi.org/10.4236/oalib.1110050.
Kassem, N., Sharaf, S., Abdel Aziz, A., et al. (2018) Towards Validation of Targeted Next-Generation Sequencing on Formalin Fixed Paraffin Embedded Colorectal Cancer Tissues in Egyptian Population: A Pilot Study with Feasibility and Challenges. International Journal of Cancer and Treatment, 1, 20-29.
Fitzmaurice, C., Allen, C., et al. (2017) Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived with Disability, and Disability-Adjusted Life-Years for 32 Cancer Groups, 1990 to 2015: A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncology, 3, 524-548.
https://doi.org/10.1001/jamaoncol.2016.5688
Murugan, A.K., Grieco, M. and Tsuchida, N. (2019) RAS Mutations in Human Cancers: Roles in Precision Medicine. Seminars in Cancer Biology, 59, 23-35.
https://doi.org/10.1016/j.semcancer.2019.06.007
Haffadi, M., Tawfiq, N., Karkouri, M., et al. (2018) RAS Status in Metastatic Colorectal Cancer: What Is the Relationship to Epidemiological and Anatomo-Clinical Factors? Annals of Oncology, 29, 79-80.
https://doi.org/10.1093/annonc/mdy151.281
El agy, F., el Bardai, S., El Otmani, I., et al. (2021) Mutation Status and Prognostic Value of KRAS and NRAS Mutations in Moroccan Colon Cancer Patients: A First Report. PLOS ONE, 16, e0248522. https://doi.org/10.1371/journal.pone.0248522
Serebriiskii, I.G., Connelly, C., Frampton, G., et al. (2019) Comprehensive Characterization of RAS Mutations in Colon and Rectal Cancers in Old and Young Patients. Nature Communications, 10, Article No. 3722.
https://doi.org/10.1038/s41467-019-11530-0
Kuchel, A., Ahern, E., Collins, S., et al. (2021) Trends in Epidemiology, Treatment and Molecular Testing of Metastatic Colorectal Cancer in a Real-World Multi-Institution Cohort Study. Asia-Pacific Journal of Clinical Oncology, 17, 84-93.
https://doi.org/10.1111/ajco.13420
Loree, J.M., Dowers, A., Tu, D., et al. (2021) Expanded Low Allele Frequency RAS and BRAF V600E Testing in Metastatic Colorectal Cancer as Predictive Biomarkers for Cetuximab in the Randomized CO.17 Trial. Clinical Cancer Research, 27, 52-59.
https://doi.org/10.1158/1078-0432.CCR-20-2710
Peeters, M., Kafatos, G., Taylor, A., et al. (2015) Prevalence of RAS Mutations and Individual Variation Patterns among Patients with Metastatic Colorectal Cancer: A Pooled Analysis of Randomised Controlled Trials. European Journal of Cancer, 51, 1704-1713. https://doi.org/10.1016/j.ejca.2015.05.017
Kassem, N.M., Emera, G., Kassem, H.A., et al. (2019) Clinicopathological Features of Egyptian Colorectal Cancer Patients Regarding Somatic Genetic Mutation Especially in KRAS Gene and Microsatellite Instability Status: A Pilot Study. Egyptian Journal of Medical Human Genetics, 20, Article No. 20.
https://doi.org/10.1186/s43042-019-0028-z
Bader, T. and Ismail, A. (2014) Higher Prevalence of KRAS Mutations in Colorectal Cancer in Saudi Arabia: Propensity for Lung Metastasis. Alexandria Journal of Medicine, 50, 203-209. https://doi.org/10.1016/j.ajme.2014.01.003
Elbjeirami, W.M. and Sughayer, M.A. (2012) KRAS Mutations and Subtyping in Colorectal Cancer in Jordanian Patients. Oncology Letters, 4, 705-710.
https://doi.org/10.3892/ol.2012.785
Kafatos, G., Niepel, D., Lowe, K., et al. (2017) RAS Mutation Prevalence among Patients with Metastatic Colorectal Cancer: A Meta-Analysis of Real-World Data. Biomarkers in Medicine, 11, 751-760. https://doi.org/10.2217/bmm-2016-0358
Al-Shamsi, H.O., Jones, J., Fahmawi, et al. (2016) Molecular Spectrum of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC Somatic Gene Mutations in Arab Patients with Colorectal Cancer: Determination of Frequency and Distribution Pattern. Journal of Gastrointestinal Oncology, 7, 882-902.
https://doi.org/10.21037/jgo.2016.11.02
Slattery, M.L., Curtin, K., et al. (2000) Associations between Dietary Intake and Ki-Ras Mutations in Colon Tumors: A Population-Based Study. Cancer Research, 60, 6935-6941.
Jayasekara, H., MacInnis, R.J., Williamson, E.J., et al. (2016) Lifetime Alcohol Intake Is Associated with an Increased Risk of KRAS and BRAF-/KRAS- but Not BRAF Colorectal Cancer. International Journal of Cancer, 140, 1485-1493.
https://doi.org/10.1002/ijc.30568
El Asri, A., Zarrouq, B., El Kinany, K., et al. (2020) Associations between Nutritional Factors and KRAS Mutations in Colorectal Cancer: A Systematic Review. BMC Cancer, 20, Article No. 696. https://doi.org/10.1186/s12885-020-07189-2
Carr, P.R., Jansen, L., Bienert, S., et al. (2017) Associations of Red and Processed Meat Intake with Major Molecular Pathological Features of Colorectal Cancer. European Journal of Epidemiology, 32, 409-418.
https://doi.org/10.1007/s10654-017-0275-6
Bruera, G., Pepe, F., Malapelle, U., et al. (2018) KRAS, NRAS and BRAF Mutations Detected by Next Generation Sequencing, and Differential Clinical Outcome in Metastatic Colorectal Cancer (MCRC) Patients Treated with First Line FIr-B/FOx Adding Bevacizumab (BEV) to Triplet Chemotherapy. Oncotarget, 9, 26279-26290.
https://doi.org/10.18632/oncotarget.25180
Bruera, G., Pepe, F., Malapelle, U., et al. (2017) Differential Clinical Outcome According to KRAS, NRAS and BRAF Genotype Detected by Massive Parallel Sequencing of Metastatic Colorectal Cancer Patients Treated with First Line FIr-B/FOx Adding Bevacizumab (BEV) to Triplet Chemotherapy. Annals of Oncology, 28, 95-96. https://doi.org/10.1093/annonc/mdx261.271
Malapelle, U., Bellevicine, C., Salatiello, M., et al. (2012) Sanger Sequencing in Routine KRAS Testing: A Review of 1720 Cases from a Pathologist’s Perspective. Journal of Clinical Pathology, 65, 940-944.
https://doi.org/10.1136/jclinpath-2012-200773
Bokemeyer, C., Van Cutsem, E., Rougier, P., et al. (2012) Addition of Cetuximab to Chemotherapy as First-Line Treatment for KRAS Wild-Type Metastatic Colorectal Cancer: Pooled Analysis of the CRYSTAL and OPUS Randomised Clinical Trials. European Journal of Cancer, 48, 1466-1475.
https://doi.org/10.1016/j.ejca.2012.02.057
Brink, M., de Goeij, A.F., Weijenberg, M.P., et al. (2003) K-RAS Oncogene Mutations in Sporadic Colorectal Cancer in the Netherlands Cohort Study. Carcinogenesis, 24, 703-710. https://doi.org/10.1093/carcin/bgg009
Slattery, M.L., Curtin, K., Schaffer, D., et al. (2002) Associations between Family History of Colorectal Cancer and Genetic Alterations in Tumors. International Journal of Cancer, 97, 823-827. https://doi.org/10.1002/ijc.10148
Boleij, A., Tack, V., Taylor, A., et al. (2016) RAS Testing Practices and RAS Mutation Prevalence among Patients with Metastatic Colorectal Cancer: Results from a Europe-Wide Survey of Pathology Centres. BMC Cancer, 16, Article No. 825.
https://doi.org/10.1186/s12885-016-2810-3
Bylsma, L.C., Gillezeau, C., Garawin, T.A., et al. (2019) Prevalence of RAS and BRAF Mutations in Metastatic Colorectal Cancer Patients by Tumor Sidedness: A Systematic Review and Meta-Analysis. Cancer Medicine, 9, 1044-1057.
https://doi.org/10.1002/cam4.2747
Rimbert, J., Tachon, G., Junca, A., et al. (2018) Association between Clinicopathological Characteristics and RAS Mutation in Colorectal Cancer. Modern Pathology, 31, 517-526. https://doi.org/10.1038/modpathol.2017.119
Guo, T.-A., Wu, Y.-C., Tan, C., et al. (2019) Clinicopathologic Features and Prognostic Value of KRAS, NRAS and BRAF Mutations and DNA Mismatch Repair Status: A Single-Center Retrospective Study of 1,834 Chinese Patients with Stage I-IV Colorectal Cancer. International Journal of Cancer, 145, 1625-1634.
https://doi.org/10.1002/ijc.32489
Liu, X., Jakubowski, M. and Hunt, J.L. (2011) KRAS Gene Mutation in Colorectal Cancer Is Correlated with Increased Proliferation and Spontaneous Apoptosis. American Journal of Clinical Pathology, 135, 245-252.
https://doi.org/10.1309/AJCP7FO2VAXIVSTP
Ta, T.V., Nguyen, Q.N., Chu, H.H., et al. (2020) RAS/RAF Mutations and Their Associations with Epigenetic Alterations for Distinct Pathways in Vietnamese Colorectal Cancer. Pathology—Research and Practice, 216, Article ID: 152898.
https://doi.org/10.1016/j.prp.2020.152898
Lee, H.S., Hwang, D.Y. and Han, H.S. (2020) Histology and Its Prognostic Effect on KRAS-Mutated Colorectal Carcinomas in Korea. Oncology Letters, 20, 655-666.
https://doi.org/10.3892/ol.2020.11606
Imamura, Y., Lochhead, P., Yamauchi, M., et al. (2014) Analyses of Clinicopathological, Molecular, and Prognostic Associations of KRAS Codon 61 and Codon 146 Mutations in Colorectal Cancer: Cohort Study and Literature Review. Molecular Cancer, 13, Article No. 135. https://doi.org/10.1186/1476-4598-13-135
Dai, D., Wang, Y., Zhu, L., et al. (2020) Prognostic Value of KRAS Mutation Status in Colorectal Cancer Patients: A Population-Based Competing Risk Analysis. PeerJ, 8, e9149. https://doi.org/10.7717/peerj.9149
Clancy, C., Burke, J.P., Kalady, M.F., et al. (2013) BRAF Mutation Is Associated with Distinct Clinicopathological Characteristics in Colorectal Cancer: A Systematic Review and Meta-Analysis. Colorectal Disease, 15, 711-718.
https://doi.org/10.1111/codi.12427
Sanz-Garcia, E., Argiles, G., Elez, E., et al. (2017) BRAF Mutant Colorectal Cancer: Prognosis, Treatment, and New Perspectives. Annals of Oncology, 28, 2648-2657.
https://doi.org/10.1093/annonc/mdx401
Li, Y. and Li, W. (2017) BRAF Mutation Is Associated with Poor Clinicopathological Outcomes in Colorectal Cancer: A Meta-Analysis. Saudi Journal of Gastroenterology, 23, 144-149. https://doi.org/10.4103/1319-3767.207712
Tie, J., Lipton, L., Desai, J., et al. (2011) KRAS Mutation Is Associated with Lung Metastasis in Patients with Curatively Resected Colorectal Cancer. Clinical Cancer Research, 17, 1122-1130. https://doi.org/10.1158/1078-0432.CCR-10-1720
Ince, W.L., Jubb, A.M., Holden, S.N., et al. (2005) Association of k-ras, b-raf, and p53 Status with the Treatment Effect of Bevacizumab. Journal of the National Cancer Institute, 97, 981-989. https://doi.org/10.1093/jnci/dji174
Westra, J.L., Schaapveld, M., Hollema, H., et al. (2005) Determination of TP53 Mutation Is More Relevant than Microsatellite Instability Status for the Prediction of Disease-Free Survival in Adjuvant-Treated Stage III Colon Cancer Patients. Journal of Clinical Oncology, 23, 5635-5643. https://doi.org/10.1200/JCO.2005.04.096
Roth, A.D., Tejpar, S., Yan, P., et al. (2009) Stage-Specific Prognostic Value of Molecular Markers in Colon Cancer: Results of the Translational Study on the PETACC 3-EORTC 40993-SAKK 60-00 Trial. Journal of Clinical Oncology, 27, Article No. 4002. https://doi.org/10.1200/jco.2009.27.15_suppl.4002
Ottaiano, A., Normanno, N., Facchini, S., et al. (2020) Study of RAS Mutations’ Prognostic Value in Metastatic Colorectal Cancer: STORIA Analysis. Cancers (Basel), 12, Article No. 1919. https://doi.org/10.3390/cancers12071919
