Determination of the frequency and distribution of APC, PIK3CA, and SMAD4 gene mutations in Ugandan patients with colorectal cancer.
APC
Africa
Colorectal cancer
Genetics
Mutation
PIK3CA
SMAD4
Uganda
Variants
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
30 Sep 2024
30 Sep 2024
Historique:
received:
06
12
2023
accepted:
19
09
2024
medline:
1
10
2024
pubmed:
1
10
2024
entrez:
30
9
2024
Statut:
epublish
Résumé
Uganda is a developing low-income country with a low incidence of colorectal cancer, which is steadily increasing. Ugandan colorectal cancer (CRC) patients are young and present with advanced-stage disease. In our population, there is a scarcity of genetic oncological studies, therefore, we investigated the mutational status of CRC tissues, focusing in particular on the adenomatous polyposis coli (APC), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), and SMAD4 genes. Our objective was to determine whether there were any differences between other populations and Ugandan patients. We performed next-generation sequencing on the extracted DNA from formalin-fixed paraffin-embedded adenocarcinoma samples from 127 patients (mean (SD) age: 54.9 (16.0) years; male:female sex ratio: 1.2:1). Most tumours were located in the rectum 56 (44.1%), 14 (11%) tumours were high grade, and 96 (75.6%) were moderate grade CRC. Stage III + IV CRC tumours were found in 109 (85.8%) patients. We identified 48 variants of APC, including 9 novel APC mutations that were all pathogenic or deleterious. For PIK3CA, we found 19 variants, of which 9 were deleterious or pathogenic. Four PIK3CA novel pathogenic or deleterious variants were included (c.1397C > G, c.2399_2400insA, c.2621G > C, c.2632C > G). Three SMAD4 variants were reported, including two pathogenic or deleterious variants (c.1268G > T, c.556dupC) and one tolerant (c.563A > C) variant. One novel SMAD4 deleterious mutation (c.1268G > T) was reported. In conclusion, we provide clinicopathological information and new genetic variation data pertinent to CRC in Uganda.
Identifiants
pubmed: 39350061
doi: 10.1186/s12885-024-12967-3
pii: 10.1186/s12885-024-12967-3
doi:
Substances chimiques
Smad4 Protein
0
Class I Phosphatidylinositol 3-Kinases
EC 2.7.1.137
PIK3CA protein, human
EC 2.7.1.137
SMAD4 protein, human
0
Adenomatous Polyposis Coli Protein
0
APC protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1212Informations de copyright
© 2024. The Author(s).
Références
Morgan E, Arnold M, Gini A, Lorenzoni V, Cabasag CJ, Laversanne M, Vignat J, Ferlay J, Murphy N, Bray F. Global burden of colorectal cancer in 2020 and 2040: incidence and mortality estimates from GLOBOCAN. Gut. 2023;72:338–44. https://doi.org/10.1136/gutjnl-2022-327736 .
doi: 10.1136/gutjnl-2022-327736
pubmed: 36604116
Xi Y, Xu P. Global colorectal cancer burden in 2020 and projections to 2040. Transl Oncol. 2021;14:101174. https://doi.org/10.1016/j.tranon.2021.101174 .
doi: 10.1016/j.tranon.2021.101174
pubmed: 34243011
pmcid: 8273208
Hamdi Y, Abdeljaoued-Tej I, Zatchi AA, Abdelhak S, Boubaker S, Brown JS, Benkahla A. Cancer in Africa: the untold story. Front Oncol. 2021;11:650117. https://doi.org/10.3389/fonc.2021.650117 .
doi: 10.3389/fonc.2021.650117
pubmed: 33937056
pmcid: 8082106
Kayamba V, Mutale W, Cassell H, Heimburger DC, Shu X-O. Systematic review of cancer research output from Africa, with zambia as an example. JCO Glob Oncol. 2021;7:802–10. https://doi.org/10.1200/GO.21.00079 .
doi: 10.1200/GO.21.00079
pubmed: 34077269
Rotimi SO, Rotimi OA, Salhia B. A review of cancer genetics and genomics studies in Africa. Front Oncol. 2021;10:606400. https://doi.org/10.3389/fonc.2020.606400 .
doi: 10.3389/fonc.2020.606400
pubmed: 33659210
pmcid: 7917259
Odedina FT, Rotimi S. Promoting cancer genomics research in Africa: a roadmap. Nat Rev Cancer. 2021;21:409–10. https://doi.org/10.1038/s41568-021-00359-9 .
doi: 10.1038/s41568-021-00359-9
pubmed: 33846603
Wismayer R. Familial adenomatous polyposis coli in east africa: a case report and review of the literature. J Adv Med Medical Res. 2020;32(17):74–80. https://doi.org/10.9734/jammr/2020/v32i1730647 .
doi: 10.9734/jammr/2020/v32i1730647
Wismayer R, Kiwanuka J, Wabinga H, Odida M. Risk factors for colorectal adenocarcinoma in an indigenous population in East Africa. Cancer Manag Res. 2022;14:2657–69. https://doi.org/10.2147/CMAR.S381479 .
doi: 10.2147/CMAR.S381479
pubmed: 36097505
pmcid: 9464000
Fadelu T, Sebahungu F, Diasti K, Nguyen C, Yeh T, Shyirambere C, Nkusi E, Nsabimana N, Ruhangaza D, DeBoer RJ, et al. Patient characteristics and outcomes of colorectal cancer (CRC) at Butaro Cancer Center of Excellence (BCCOE): results from a retrospective cohort. J Clin Oncol. 2020;38(Suppl. 15):e16081.
doi: 10.1200/JCO.2020.38.15_suppl.e16081
Uwamariya D, Ruhangaza D, Rugwizangoga B. Pathological characteristics, prognostic determinants and the outcome of patients diagnosed with colorectal adenocarcinoma at the University Teaching Hospital of Kigali. Can J Gastroenterol Hepatol. 2022;2022:6608870.
pubmed: 36247044
pmcid: 9553703
doi: 10.1155/2022/6608870
Mc Cubrey JA, Steelman LS, Chappell WH, Abrams SL, Wong EWT, Chang F, Lehmann B, et al. Roles of the RAF/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. Molecular Cell Res. 2007;1773(8):1263–84.
Zhang Y, Zhang XO, Chen T, Xiang JF, Yin QF, Xing YH, Zhu S, Yang L, Chen LL. Circular intronic long noncoding RNAs. Mol Cell. 2013;51:792–806.
pubmed: 24035497
doi: 10.1016/j.molcel.2013.08.017
Alatise OI, Knapp GC, Sharma A, Chatila WK, Arowolo OA, Olasehinde O, Famurewa OC, Omisore AD, Komolafe AO, Olaofe OO, et al. Molecular and phenotypic profiling of colorectal cancer patients in West Africa reveals biological insights. Nat Commun. 2021;12:6821.
pubmed: 34819518
pmcid: 8613248
doi: 10.1038/s41467-021-27106-w
Guda K, Veigl ML, Varadan V, Nosrati A, Ravi L, Lutterbaugh J, Beard L, Willson JKV, Sedwick WD, Wang ZJ, et al. Novel recurrently mutated genes in African American colon cancers. Proc Natl Acad Sci USA. 2015;112:1149–54. https://doi.org/10.1073/pnas.1417064112 .
doi: 10.1073/pnas.1417064112
pubmed: 25583493
pmcid: 4313860
Myer PA, Lee JK, Madison RW, Pradhan K, Newberg JY, Isasi CR, Klempner SJ, Frampton GM, Ross JS, Venstrom JM, et al. The Genomics of colorectal cancer in populations with African and European ancestry. Cancer Discov. 2022;12:1282–93.
pubmed: 35176763
pmcid: 9169495
doi: 10.1158/2159-8290.CD-21-0813
Augustus GJ, Ellis NA. Colorectal cancer disparity in African Americans: risk factors and carcinogenic mechanisms. Am J Pathol. 2018;188:291–303. https://doi.org/10.1016/j.ajpath.2017.07.023 .
doi: 10.1016/j.ajpath.2017.07.023
pubmed: 29128568
pmcid: 5785537
Aoki K, Taketo MM. Adenomatous polyposis coli (APC): a multi-functional tumor suppressor gene. J Cell Sci. 2007;120:3327–35.
pubmed: 17881494
doi: 10.1242/jcs.03485
Schell MJ, Yang M, Teer JK, Lo FY, Madan A, Coppola D, Monteiro ANA, Nebozhyn MV, Yue B, Loboda A, et al. A multigene mutation classification of 468 colorectal cancers reveals a prognostic role for APC. Nat Commun. 2016;7:11743.
pubmed: 27302369
pmcid: 4912618
doi: 10.1038/ncomms11743
Samuels Y, Wang Z, Bardelli A, Sillman N, Ptak J, Szabo S, Yan H, et al. High frequency of mutations of the PIK3CA gene in human cancers. Science. 2004;304(5670):554.
pubmed: 15016963
doi: 10.1126/science.1096502
Peyssonnaux C, Eychene A. The Raf/MEK/ERK pathway: new concepts of activation. Biol Cell. 2001;93:53–62.
pubmed: 11730323
doi: 10.1016/S0248-4900(01)01125-X
Calistri D, Rengucci C, Seymour I, Lattuneddu A, Polifemo AM, Monti F, Saragoni L, Amadori D. Mutation analysis of p53, K-ras, and BRAF genes in colorectal cancer progression. J Cell Physiol. 2005;204(2):484–8.
pubmed: 15702478
doi: 10.1002/jcp.20310
Irabor DO, Oluwasola OA, Ogunbiyi OJ, Ogun OG, Okolo CA, Melas M, Gruber SB, Shi C, Raskin L. Microsatellite instability is common in colorectal cancer in native Nigerians. Anticancer Res. 2017;37:2649–54.
pubmed: 28476840
doi: 10.21873/anticanres.11612
He Y, Mou Z, Li W, et al. Identification of IMPDH2 as a tumor-associated antigen in colorectal cancer using immunoproteomics analysis. Int J Colorectal Dis. 2009;24:1271–9.
pubmed: 19597826
doi: 10.1007/s00384-009-0759-2
Whitehall VLJ, Riekman C, Bond CE, Ramsnes I, Greco SA, et al. Oncogenic PIK3CA mutations in colorectal cancers and polyps. Cancer Genet. 2011;131(4):813–20.
De Roock W, Claes B, Bernasconi D, De Schutter J, Biesmans B, Fountzilas G, Kalogeras KT, Kotoula V, Papamichael D, Laurent-Puig P, Penault-Llorca F, Rougier P, Vincenzi B, Santini D, Tonini G, Cappuzzo F, Frattini M, Molinari F, Saletti P, De Dosso S, Martini M, Bardelli A, Siena S, Sartore-Bianchi A, Tabernero J, Macarulla T, Di Fiore F, Gangloff AO, Ciardiello F, Pfeiffer P, Qvortrup C, Hansen TP, Van Cutsem E, Piessevaux H, Lambrechts D, Delorenzi M, Tejpar S. Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol. 2010;11(8):753–62.
pubmed: 20619739
doi: 10.1016/S1470-2045(10)70130-3
Mao C, Zhou J, Yang Z, Huang Y, Wu X, Shen H, et al. KRAS, BRAF and PIK3CA mutations and the loss of PTEN expression in chinese patients with colorectal cancer. PLoS One. 2012;7(5):e36653.
pubmed: 22586484
pmcid: 3346734
doi: 10.1371/journal.pone.0036653
Liao X, Lochhead P, Nishihara R, Morikawa T, Kuchiba A, Yamauchi M, Imamura Y, Qian ZR, Baba Y, Shima K, Sun R, Nosho K, Meyerhardt JA, Giovannucci E, Fuchs CS, Chan AT, Ogino S. Aspirin use, tumor PIK3CA mutation, and colorectal-cancer survival. N Engl J Med. 2012;367(17):1596–606.
pubmed: 23094721
pmcid: 3532946
doi: 10.1056/NEJMoa1207756
Barault L, Charon-Barra C, Jooste V, de la Vega MF, Martin L, Roignot P, et al. Hypermethylator phenotype in sporadic colon cancer: study on a population-based series of 582 cases. Cancer Res. 2008;68:8541–6.
pubmed: 18922929
doi: 10.1158/0008-5472.CAN-08-1171
Lièvre A, Blons H, Laurent-Puig P. Oncogenic mutations as predictive factors in colorectal cancer. Oncogene. 2010;29:3033–43. https://doi.org/10.1038/onc.2010.89 .
doi: 10.1038/onc.2010.89
pubmed: 20383189
Vaish V, Tanwar L, Kaur J, et al. Chemopreventive effects of non-steroidal anti-inflammatory drugs in early neoplasm of experimental colorectal cancer: an apoptosome study. J Gastrointest Canc. 2011;42:195–203.
doi: 10.1007/s12029-010-9188-2
Bavi P, Prabhakaran SE, Abubaker J, et al. Prognostic significance of TRAIL death receptors in Middle Eastern colorectal carcinomas and their correlation to oncogenic KRAS alterations. Mol Cancer. 2010;9:203.
pubmed: 20673328
pmcid: 2922191
doi: 10.1186/1476-4598-9-203
Nishihara R, Wu K, Lochhead P, Morikawa T, et al. Long-term colorectal cancer incidence and mortality after lower endoscopy. N Engl J Med. 2013;369:1095–105.
pubmed: 24047059
doi: 10.1056/NEJMoa1301969
Itatani Y, Kawada K, Sakai Y. Transforming growth factor-β signaling pathway in colorectal cancer and its tumor microenvironment. Int J Mol Sci. 2019;20(23):5822.
pubmed: 31756952
pmcid: 6929101
doi: 10.3390/ijms20235822
Calonge MJ, Massague J. SMAD4/DPC4 silencing and hyperactive RAS jointly disrupt transforming growth factor-β antiproliferative responses in colon cancer cells. Cell Biol Metabolism. 1999;274(47):33637–43.
Shovlin CL, Simeoni I, Downes K, Frazer ZC, Megy K, et al. Mutational and phenotypic characterization of hereditary haemorrhagic telangiectasia. Clin Trials Observ. 2020;136(17):1907–18.
McCarthy AJ, Chetty R. SMAD4/DPC4. J Clin Pathol. 2018;71(8):1–7.
doi: 10.1136/jclinpath-2018-205095
Liu HJ, Luan X, Feng HY, Dong X, Yang Si-C, Chen ZJ, et al. Integrated combination treatment using a “smart” chemotherapy and microRNA Delivery system improes outcomes in an orthotopic colorectal cancer model. Adv Funct Mater. 2018;28(28):1801118.
doi: 10.1002/adfm.201801118
Huang D, Sun W, Zhou Y, et al. Mutations of key driver genes in colorectal cancer progression and metastasis. Cancer Metastasis Rev. 2018;37:173–87.
pubmed: 29322354
doi: 10.1007/s10555-017-9726-5
Sudo M, Furuya S, Shimizu H, et al. Long-term outcomes after surgical resection in patients with stage IV colorectal cancer: a retrospective study of 129 patients at a single institution. World J Surg Onc. 2019;17:56.
doi: 10.1186/s12957-019-1599-3
Miyaki M, Iijima T, Kimura J, Yasuno M, Mori T, Hayashi Y, Koike M, Shitara N, Iwama T, Kuroki T. Frequent mutation of β-catenin and APC genes in primary colorectal tumours from patients with hereditary nonpolyposis colorectal cancer. Can Res. 1999;59(18):4506–9.
Mizuno T, Cloyd JM, Vicente D, Omichi K, Chun YS, Kopetz SE, Maru D, Conrad C, Tzeng CD, Wei SH, Aloia TA, Vauthey JN. SMAD4 gene mutation predicts poor prognosis in patients undergoing resection for colorectal liver metastases. Eur J Surg Oncol. 2018;44(5):684–92.
pubmed: 29551247
doi: 10.1016/j.ejso.2018.02.247
Mehrvarz Sarshekeh A, Advani S, Overman MJ, Manyam G, Kee BK, Fogelman DR, Dasari A, Raghav K, Vilar E, Manuel S, Shureiqi I, Wolff RA, Patel KP, Luthra R, Shaw K, Eng C, Maru DM, Routbort MJ, Meric-Bernstam F, Kopetz S. Association of SMAD4 mutation with patient demographics, tumor characteristics, and clinical outcomes in colorectal cancer. PLoS One. 2017;12(3):e0173345. https://doi.org/10.1371/journal.pone.0173345 . Erratum.In:PLoSOne.2017May17;12(5):e0178275.
doi: 10.1371/journal.pone.0173345
pubmed: 28267766
Fleming NI, Jorissen RN, Mouradov D, Christie M, Sakthianandeswaren A, Palmieri M, Day F, Li S, Tsui C, Lipton L, Desai J, Jones IT, McLaughlin S, Ward RL, Hawkins NJ, Ruszkiewicz AR, Moore J, Zhu HJ, Mariadason JM, Burgess AW, Busam D, Zhao Q, Strausberg RL, Gibbs P, Sieber OM. SMAD2, SMAD3 and SMAD4 mutations in colorectal cancer. Cancer Res. 2013;73(2):725–35.
pubmed: 23139211
doi: 10.1158/0008-5472.CAN-12-2706
Fang T, Liang T, Wang Y, et al. Prognostic role and clinicopathological features of SMAD4 gene mutation in colorectal cancer: a systematic review and meta-analysis. BMC Gastroenterol. 2021;21:297. https://doi.org/10.1186/s12876-021-01864-9 .
doi: 10.1186/s12876-021-01864-9
pubmed: 34301194
pmcid: 8299661
Lee CS, Song IH, Lee A, et al. Enhancing the landscape of colorectal cancer using targeted deep sequencing. Sci Rep. 2021;11:8154. https://doi.org/10.1038/s41598-021-87486-3 .
doi: 10.1038/s41598-021-87486-3
pubmed: 33854094
pmcid: 8046812
Maitra A, Molberg K, Albores-Saavedra J, Lindberg G. Loss of Dpc4 expression in colonic adenocarcinomas correlates with the presence of metastatic disease. Am J Pathol. 2000;157(4):1105–11.
pubmed: 11021814
pmcid: 1850169
doi: 10.1016/S0002-9440(10)64625-1
QIAseq library preparation workflow (adapted from QIAseq Targeted DNA Pro Handbook Page 11).
Landrum MJ, Lee JM, Benson M, Brown GR, Chao C, Chitipiralla S, Gu B, Hart J, Hoffman D, Jang W, Karapetyan K, Katz K, Liu C, Maddipatla Z, Malheiro A, McDaniel K, Ovetsky M, Riley G, Zhou G, Holmes JB, Kattman BL, Maglott DR. ClinVar: improving access to variant interpretations and supporting evidence. Nucleic Acids Res. 2018;46(1):1062–7 https://pubmed.ncbi.nlm.nih.gov/29165669/ .
doi: 10.1093/nar/gkx1153
Alirezaie N, Kernohan KD, Hartley T, Majewski J, Hocking TD. ClinPred: prediction tool to identify disease-relevant nonsynonymous single-nucleotide variants. Am J Hum Genetics. 2018;103(4):474–83.
doi: 10.1016/j.ajhg.2018.08.005
Andrews S. FastQC: a quality control tool for high throughput sequence data. In: Cambridge, United Kingdom. 2010.
Kopanos C, Tsiolkas V, Kouris A, Chapple CE, Aguilera MA, Meyer R, Massouras A. VarSome: the human genomic variant search engine. Bioinformatics. 2019;35(11):1978.
pubmed: 30376034
doi: 10.1093/bioinformatics/bty897
Lek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E, Fennell T, O’Donnell-Luria AH, Ware JS, Hill AJ, Cummings BB. Analysis of protein-coding genetic variation in 60,706 humans. Nature. 2016;536(7616):285–91.
pubmed: 27535533
pmcid: 5018207
doi: 10.1038/nature19057
Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009;25(14):1754–60.
pubmed: 19451168
pmcid: 2705234
doi: 10.1093/bioinformatics/btp324
Krueger F, Galore T. A wrapper tool around Cutadapt and FastQC to consistently apply quality and adapter trimming to FastQ files. Cambridge: Babraham Institute; 2015.
McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, Garimella K, Altshuler D, Gabriel S, Daly M. The genome analysis toolkit: a mapreduce framework for analyzing next-generation DNA sequencing data. Genome Res. 2010;20(9):1297–303.
pubmed: 20644199
pmcid: 2928508
doi: 10.1101/gr.107524.110
Choi Y, Sims GE, Murphy S, Miller JR, Chan AP. Predicting the functional effect of amino acid substitutions and indels. 2012.
doi: 10.1371/journal.pone.0046688
Ewels P, Magnusson M, Lundin S, Käller M. MultiQC: summarize analysis results for multiple tools and samples in a single report. Bioinformatics. 2016;32(19):3047–8.
pubmed: 27312411
pmcid: 5039924
doi: 10.1093/bioinformatics/btw354
Consortium, G. P, Auton A, Brooks L, Durbin R, Garrison E, Kang H. A global reference for human genetic variation. Nature. 2015;526(7571):68-74
Li B, Krishnan VG, Mort ME, Xin F, Kamati KK, Cooper DN, Mooney SD, Radivojac P. Automated inference of molecular mechanisms of disease from amino acid substitutions. Bioinformatics. 2009;25(21):2744–50.
pubmed: 19734154
pmcid: 3140805
doi: 10.1093/bioinformatics/btp528
Chun S, Fay JC. Identification of deleterious mutations within three human genomes. Genome Res. 2009;19(9):1553–61.
pubmed: 19602639
pmcid: 2752137
doi: 10.1101/gr.092619.109
Dong C, Wei P, Jian X, Gibbs R, Boerwinkle E, Wang K, Liu X. Comparison and integration of deleteriousness prediction methods for nonsynonymous SNVs in whole exome sequencing studies. Hum Mol Genet. 2015;24(8):2125–37.
pubmed: 25552646
doi: 10.1093/hmg/ddu733
Forbes SA, Beare D, Gunasekaran P, Leung K, Bindal N, Boutselakis H, Ding M, Bamford S, Cole C, Ward S. COSMIC: exploring the world’s knowledge of somatic mutations in human cancer. Nucleic Acids Res. 2015;43(D1):D805–11.
pubmed: 25355519
doi: 10.1093/nar/gku1075
Karczewski KJ, Francioli LC, Tiao G, Cummings BB, Alföldi J, Wang Q, Collins RL, Laricchia KM, Ganna A, Birnbaum DP. The mutational constraint spectrum quantified from variation in 141,456 humans. Nature. 2020;581(7809):434–43.
pubmed: 32461654
pmcid: 7334197
doi: 10.1038/s41586-020-2308-7
Landrum MJ, Lee JM, Benson M, Brown GR, Chao C, Chitipiralla S, Gu B, Hart J, Hoffman D, Jang W. ClinVar: improving access to variant interpretations and supporting evidence. Nucleic Acids Res. 2018;46(D1):D1062–7.
pubmed: 29165669
doi: 10.1093/nar/gkx1153
Dijxhoorn DN, Boutall A, Mulder CJ, Ssebuufu R, Mall A, Kalungi S, Baigrie C, Goldberg PA. Colorectal cancer in patients from Uganda: a histopathological study. East Central Afr J Surg. 2014;19(1):112–9.
Makobore P, Masiira-Mukasa N, Elobu E. P-0283 Characterisation of colorectal carcinoma in Uganda: is Ugandan Tumour unique? Ann Oncol. 2012;23(4):112.
doi: 10.1016/S0923-7534(20)30215-5
Manirakiza F, Rutaganda E, Yamada H, Iwashita Y, Rugwizangoga B, Seminega B, Dusabejambo V, Ntakirutimana G, Ruhangaza D, Uwineza A, Shinmura K, Sugimura H. Clinicopathological Characteristics and Mutational Landscape of APC, HOXB13, and KRAS among Rwandan Patients with Colorectal Cancer. Curr Issues Mol Biol. 2023;45(5):4359–74.
pubmed: 37232746
pmcid: 10217012
doi: 10.3390/cimb45050277
Chiorean EG, Nandakumar G, Fadelu T, et al. Treatment of patients with late-stage colorectal cancer: ASCO resource-stratified guideline. JCO Glob Oncol. 2020;6:414–38. https://doi.org/10.1200/JGO.19.00367 .
doi: 10.1200/JGO.19.00367
pubmed: 32150483
Uwamariya D, Ruhangaza D, Rugwizangoga B. Pathological characteristics, prognostic determinants and the outcome of patients diagnosed with colorectal adenocarcinoma at the University Teaching Hospital of Kigali. Can J Gastroenterol Hepatol. 2022;20(2022):6608870.
Wismayer R, Kiwanuka J, Wabinga H, Odida M. Colorectal adenocarcinoma in Uganda: are right-sided and left-sided colon cancers two distinct disease entities? World J Surg Oncol. 2023;21:215.
pubmed: 37480083
pmcid: 10362740
doi: 10.1186/s12957-023-03094-7
Wekha G, Ssewante N, Iradukunda A, Jurua M, Nalwoga S, Lanyero S, Olum R, Bongomin F. Colorectal cancer in Uganda: a 10-year, facility-based. Retrospective Study Cancer Manag Res. 2021;7(13):7697–707.
Lam AK, Chan SS, Leung M. Synchronous colorectal cancer: clinical, pathological and molecular implications. World J Gastroenterol. 2014;20(22):6815–20. https://doi.org/10.3748/wjg.v20.i22.6815 .
doi: 10.3748/wjg.v20.i22.6815
pubmed: 24944471
pmcid: 4051920
Udofot MIA, Ekpo SU, MD , Khalil. Familial polyposis coli: an unusual case in West Africa. Cent Afr J Med. 1992;38(1):44–48.
Kakembo N, Kisa P, Fitzgerald T, Ozgediz D, Sekabira J. Colonic polyposis in a 15-year-old boy: Challenges and lessons from a rural resource-poor area. Ann Med Surg. 2016;7:75–8.
doi: 10.1016/j.amsu.2016.03.027
Wismayer R. A narrative review on colorectal adenocarcinoma in East Africa. Highlights Med Medical Res. 2020;1(4):27–38.
Alese OB, Irabor DO. Adenomatous polyposis coli in an elderly female Nigerian. Ghana Med J. 2009;43(3):139–41.
pubmed: 20126328
pmcid: 2810243
Boyuwoye MO, Olekoba AS, Ogunlaja OA, Agodirin SO, Ibrahim OK, Okonkwo KC, Aliyu AM. Familial adenomatous polyposis syndrome with colorectal cancer in two Nigerians: a report of two cases and review of literature. Pan Afr Med J. 2018;30(1):1–5.
Kiringa KS, Zalzal MC, Bahizi KE, Hangi MS, Bartels SA. Familial adenomatous polyposis (FAP): a case observed in eastern Democratic Republic of the Congo. Afr J Gastroenterol Hepatol. 2022;5(1):32–9.
doi: 10.21608/ajgh.2022.120465.1003
Lüchtenborg M, Weijenberg MP, Roemen GM, de Bruïne AP, van den Brandt PA, Lentjes MH, Brink M, van Engeland M, Goldbohm RA, de Goeij AF. APC mutations in sporadic colorectal carcinomas from The Netherlands Cohort Study. Carcinogenesis. 2004;25(7):1219–26.
pubmed: 14976131
doi: 10.1093/carcin/bgh117
Miki Y, Nishisho I, Horii A, Miyoshi Y, Utsunomiya J, Kinzler KW, Vogelstein B, Nakamura Y. Disruption of the APC gene by a retrotransposal insertion of L1 sequence in a colon cancer1. Cancer Res. 1992;52(3):643–5.
pubmed: 1310068
Kruse R, Rutten A, Lamberti C, Hosseiny-Malayeri HR, Wang Y, Ruelfs C, Jungck M, Mathiak M, Ruzieka T, Hartschuh W, Bisceglia M, Friedl W, Propping P. Am J Hum Genet. 1998;63:63–70.
Phipps A, Buchanan D, Makar K, et al. KRAS-mutation status in relation to colorectal cancer survival: the joint impact of correlated tumour markers. Br J Cancer. 2013;108:1757–64. https://doi.org/10.1038/bjc.2013.118 .
doi: 10.1038/bjc.2013.118
pubmed: 23511557
pmcid: 3668469
Day FL, Jorissen RN, Lipton L, Mouradov D, Sakthianadeswaren A, Christie M, Li S, Tsui C, Tie J, Desai J, et al. PIK3CA and PTEN gene and exon mutation-specific clinicopathologic and molecular associations in colorectal cancer. Clin Cancer Res. 2013;19(12):3285–96.
pubmed: 23633456
doi: 10.1158/1078-0432.CCR-12-3614
Ogino S, Nosho K, Kirkner GJ, et al. CpG island methylator phenotype microsatellite instability BRAF mutation and clinical outcome in colon cancer. Gut. 2009;58:90–6.
pubmed: 18832519
doi: 10.1136/gut.2008.155473
Nosho K, Kawasaki T, Ohnishi M, Suemoto Y, Kirkner GJ, Zepf D, Yan L, Longtine JA, Fuchs CS, Ogino S. PIK3CA mutation in colorectal cancer: relationship with genetic and epigenetic alterations. Neoplasia. 2008;10(6):534–41.
pubmed: 18516290
pmcid: 2386538
doi: 10.1593/neo.08336
Tsong W, Koh WP, Yuan JM, et al. Cigarettes and alcohol in relation to colorectal cancer: the Singapore Chinese health study. Br J Cancer. 2007;96:821–7. https://doi.org/10.1038/sj.bjc.6603623 .
doi: 10.1038/sj.bjc.6603623
pubmed: 17311023
pmcid: 2360085
Shen Y, Wang J, Han X, Yang H, Wang S, Lin D, et al. Effectors of epidermal growth factor receptor pathway: the genetic profiling of KRAS, BRAF, PIK3CA, NRAS mutations in colorectal cancer characteristics and personalized medicine. PLoS One. 2013;8(12):e81628. https://doi.org/10.1371/journal.pone.0081628 .
doi: 10.1371/journal.pone.0081628
pubmed: 24339949
pmcid: 3858242
Chong ML, Lol M, Thakkar B, Pang B, Iacopetta B, Soong R. Phosphatidylinositol-3-kinase pathway aberrations in gastric and colorectal cancer. Meta-analysis, co-occurrence and ethnic variation. Cancer Therapy. 2013;134(5):1232–8.
Rosty C, Young JP, Walsh MD, Clendenning M, Sanderson K, Walters RJ, et al. PIK3CA activating mutation in colorectal carcinoma: associations with molecular features and survival. PLoS One. 2013;8(6):e65479. https://doi.org/10.1371/journal.pone.0065479 .
doi: 10.1371/journal.pone.0065479
pubmed: 23785428
pmcid: 3681782
Janku F, Lee JJ, Tsimberidou AM, Hong DS, Naing A, Falchook GS, et al. PIK3CA mutations frequently coexist with RAS and BRAF mutations in patients with advanced cancers. PLoS One. 2011;6(7):e22769. https://doi.org/10.1371/journal.pone.0022769 .
doi: 10.1371/journal.pone.0022769
pubmed: 21829508
pmcid: 3146490
Cathomas G. PIK3CA in colorectal cancer. Front Oncol. 2014;4:35. https://doi.org/10.3389/fonc.2014.00035 .
doi: 10.3389/fonc.2014.00035
pubmed: 24624362
pmcid: 3939771
Fariña-Sarasqueta A, Gosens MJEM, Moerland E, et al. TS gene polymorphisms are not good markers of response to 5-FU therapy in stage III colon cancer patients. Cell Oncol. 2011;34:327–35. https://doi.org/10.1007/s13402-011-0030-z .
doi: 10.1007/s13402-011-0030-z
Chan AT, Ogino S, Fuchs CS. Aspirin use and survival after diagnosis of colorectal cancer. JAMA. 2009;302(6):649–58. https://doi.org/10.1001/jama.2009.1112 .
doi: 10.1001/jama.2009.1112
pubmed: 19671906
pmcid: 2848289
Domingo E, Church DN, Sieber O, Ramamoorthy R, Yanagisawa Y, Johnstone E, Davidson B, Kerr DJ, Tomlinson I, Midgley R. Evaluation of PIK3CA mutation as a predictor of benefit from non-steroidal anti-inflammatory drug therapy in colorectal cancer. J Clin Oncol. 2013;31(34):4297–305.
pubmed: 24062397
doi: 10.1200/JCO.2013.50.0322
Li P, Wu H, Zhang H, et al. Aspirin use after diagnosis but not prediagnosis improves established colorectal cancer survival: a meta-analysis. Gut. 2015;64:1419–25.
pubmed: 25239119
doi: 10.1136/gutjnl-2014-308260
Paleari L, Puntoni M, Clavarezza M, DeCensi M, Cuzick J, DeCensi A. PIK3CA mutation, aspirin use after diagnosis and survival of colorectal cancer. A systematic review and meta-analysis of epidemiological studies. Clin Oncol. 2016;28(5):317–26.
doi: 10.1016/j.clon.2015.11.008
Ogino S, Lochhead P, Giovannucci E, et al. Discovery of colorectal cancer PIK3CA mutation as potential predictive biomarker: power and promise of molecular pathological epidemiology. Oncogene. 2014;33:2949–55. https://doi.org/10.1038/onc.2013.244 .
doi: 10.1038/onc.2013.244
pubmed: 23792451
Yano H, Saito Y, Kirihara Y, et al. Tumor Invasion of Lymph Node Capsules in Patients with Dukes C Colorectal Adenocarcinoma. Dis Colon Rectum. 2006;49:1867–77. https://doi.org/10.1007/s10350-006-0733-9 .
doi: 10.1007/s10350-006-0733-9
pubmed: 17080279
Sakhila K. Banu, JeHoon Lee, V. O. Speights, Anna Starzinski-Powitz, Joe A. Arosh, Selective Inhibition of Prostaglandin E2 Receptors EP2 and EP4 Induces Apoptosis of Human Endometriotic Cells through Suppression of ERK1/2, AKT, NFκB, and β-Catenin Pathways and Activation of Intrinsic Apoptotic Mechanisms. Mol Endocrinol. 2009;23(8):1291–1305. https://doi.org/10.1210/me.2009-0017 .
Maria Domenica Castellone et al.Prostaglandin E<sub>2</sub> Promotes Colon Cancer Cell Growth Through a G<sub>s</sub>-Axin-ß-Catenin Signaling Axis. Science. 2005;310:1504–1510. https://doi.org/10.1126/science.1116221 .
Li W, Chang J, Wang S, Liu X, Peng J, Huang D, Sun M, Chen Z, Zhang W, Guo W, Li J. miRNA-99b-5p suppresses liver metastasis of colorectal cancer by down-regulating mTOR. Oncotarget. 2015;6(27):24448–62.
pubmed: 26259252
pmcid: 4695197
doi: 10.18632/oncotarget.4423
Buchanan FG, Gorden DL, Matta P, Dubois RN. Role of β-arrestin 1 in the metastatic progression of colorectal cancer. PNAS. 2006;103(5):1492–7.
pubmed: 16432186
pmcid: 1360588
doi: 10.1073/pnas.0510562103
Regan JW. EP2 and EP4 prostanoid receptor signalling. Life Sci. 2003;74(2–3):143–53.
pubmed: 14607241
doi: 10.1016/j.lfs.2003.09.031
Wosiak A, Wodziński D, Michalska K, Pietrzak J, Kordek R, Balcerczak E. Assessment of the role of selected SMAD3 and SMAD4 genes polymorphisms in the development of colorectal cancer: preliminary research. Pharmgenomics Pers Med. 2021;29(14):167–78.
Xie W, Rimm DL, Lin Y, Shih WJ, Reiss M. Loss of smad signaling in human colorectal cancer is associated with advanced disease and poor prognosis. Cancer J. 2003;9(4):302–12.
pubmed: 12967141
doi: 10.1097/00130404-200307000-00013
Alazzouzi H, Ahopuro P, Salovaara R, Sammalkorpi H, Jarvinen H, Mecklin J-P, Hemminki A, Schwartz S, Aaltonen LA, Arango D. SMAd4 as a prognostic marker in colorectal cancer. Clin Cancer Res. 2005;11(7):2606–11.
pubmed: 15814640
doi: 10.1158/1078-0432.CCR-04-1458
Slattery ML, Herrick JS, Lundgreen A, Wolff RK. Genetic variation in the TGF-β signalling pathway and colon and rectal cancer risk. Cancer Epidemiol Biomarkers Prev. 2011;20(1):57–69.
pubmed: 21068203
doi: 10.1158/1055-9965.EPI-10-0843
Lanza G, Matteuzzi M, Gafa R, Orvieto E, Maestri I, Santini A, Del Senno L. Chromosome 18q allelic loss and prognosis in stage II and III colon cancer. Human Cancer. 1998;79(4):390–5.
Flanagan FL, Dehdashti F, Ogunbiyi OA, Kodner IJ, Siegel BA. Utility of FDG-PET for investigating unexplained plasma CEA elevation in patients with colorectal cancer. Ann Surg. 1998;227(3):319–23.
pubmed: 9527052
pmcid: 1191267
doi: 10.1097/00000658-199803000-00001
Diep CB, Thorstensen L, Meling GI, Skovlund E, Rognum TO, Lothe RA. Genetic tumor markers with prognostic impact in Dukes’ stages B and C colorectal cancer patients. J Clin Oncol. 2003;21(5):820–9.
pubmed: 12610180
doi: 10.1200/JCO.2003.05.190
Cohn KH, Ornstein DL, Wang F, LaPaix FD, Phipps BAK, et al. The significance of allelic deletions and aneuploidy in colorectal carcinoma. Cancer. 2000;79(2):233–44.
doi: 10.1002/(SICI)1097-0142(19970115)79:2<233::AID-CNCR6>3.0.CO;2-L
Jen J, Kim H, Piantadosi S, Liu Z-F, Levitt RC, Sistonen P, Kinzler KW, Vogelstein B, Hamilton SR. Allelic loss of chromosome 18q and prognosis in colorectal cancer. N Eng J Med. 1994;331:213–21.
doi: 10.1056/NEJM199407283310401
Laurent-Puig P, Olschwang S, Delattre O, Remvikos Y, Asselain B, Melot T, Validire P, Muleris M, Girodet J, Salmon RJ, et al. Survival and acquired genetic alterations in colorectal cancer. Gastroenterology. 1992;102(4):1136–41.
pubmed: 1551522
doi: 10.1016/0016-5085(92)90749-O
Soliman A, Bondy M, El-Badawy S, et al. Contrasting molecular pathology of colorectal carcinoma in Egyptian and Western patients. Br J Cancer. 2001;85:1037–46. https://doi.org/10.1054/bjoc.2001.1838 .
doi: 10.1054/bjoc.2001.1838
pubmed: 11592777
pmcid: 2375101
Alhopuro P, Alazzouzi H, Sammalkorpi H, Davalos V, Salovaara R, Hemminki A, Jarvinen H, Mecklin J-P, Schwatz S, Aaltonen LA, Arango D. SMAD4 levels and response to 5-fluorouracil in colorectal cancer. Clin Cancer Res. 2005;11(17):6311–6.
pubmed: 16144935
doi: 10.1158/1078-0432.CCR-05-0244
Martin M. Catadapt removes adapter sequences from high-throughput sequencing reads. EMBnet.journal, [S.I] 2011;17(1):10–12. Available at: https://journal.embnet.org/index.php/embnetjournal/article/view/200/479 .
Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009;25(14):1754–60. https://pubmed.ncbi.nlm.nih.gov/19451168/ .
Van der Auwera GA, Carneiro MO, Hartl C, Poplin R, Del Angel G, Levy-Moonshine A, Jordan T, Shakir K, Roazen D, Thibault J, Banks E, Garimella KV, Altshuler D, Gabriel S, DePristo MA. From FastQ data to high confidence variant calls: the Genome Analysis Toolkit best practices pipeline. Curr Protoc Bioinformatics. 2013;43(1110):11.10.1–11.10.33. https://pubmed.ncbi.nlm.nih.gov/25431634/ .
Wang K, Li M, HaKonarson H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic acids Res. 2010;38(16):e164. https://pubmed.ncbi.nlm.nih.gov/20601685/ .
Ng PC, Henikoff S. Predicting deleterious amino acid substitutions. Genome Res. 2001;11(5):863–74.
pubmed: 11337480
pmcid: 311071
doi: 10.1101/gr.176601
Picard E, Verschoor CP, Ma GW, Pawelec G. Relationships between immune landscapes, genetic subtypes and responses to immunotherapy in colorectal cancer. Front Immunol. 2020;6(11):369.
doi: 10.3389/fimmu.2020.00369
Nazemalhosseini Mojarad E, Kuppen PJ, Aghdaei HA, Zali MR. The CpG island methylator phenotype (CIMP) in colorectal cancer. Gastroenterol Hepatol Bed Bench. 2013 Summer;6(3):120–8.
Kanthan R, Senger JL, Kanthan SC. Molecular events in primary and metastatic colorectal carcinoma: a review. Patholog Res Int. 2012;2012: 597497.
pubmed: 22997602
pmcid: 3357597
Ewing I, Hurley JJ, Josephides E, Millar A. The molecular genetics of colorectal cancer. Frontline Gastroenterol. 2014;5(1):26–30.
pubmed: 24416503
doi: 10.1136/flgastro-2013-100329
Testa U, Pelosi E, Castelli G. Colorectal cancer: genetic abnormalities, tumor progression, tumor heterogeneity, clonal evolution and tumor-initiating cells. Med Sci (Basel). 2018;6(2):31.
pubmed: 29652830
Armaghany T, Wilson JD, Chu Q, Mills G. Genetic alterations in colorectal cancer. Gastrointest Cancer Res. 2012;5(1):19–27.
pubmed: 22574233
pmcid: 3348713