{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:09:52Z","timestamp":1760144992307,"version":"build-2065373602"},"reference-count":47,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T00:00:00Z","timestamp":1717718400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gastrointestinal Disorders"],"abstract":"<jats:p>Colorectal cancer (CRC) outcomes in terms of incidence and mortality are significantly worse in African Americans than other Americans. While differences in primary preventions for neoplasia (diet, obesity remediation, aspirin prophylaxis) are being elucidated, genetic mutations affecting premalignant lesions and immune response mechanisms may possibly also explain the increased incidence and mortality, particularly from right-sided disease. Objective: Our team therefore examined colonic segments seeking to test the hypothesis that the immune response and somatic genetic profiles of the colonic anatomic segments may vary and thus account for variations in neoplasia risk among the various colonic segments revealing an antigenic relationship with precancerous lesions. The p87 antigenic field effect is recognized via Adnab-9 antibody immunohistochemistry to be significantly less in the right colon in African Americans, particularly in the cecum. Method: Since small high-grade dysplastic adenomas (SHiGDA) likely missed by CRC screening may progress to cancer, we used Ion Torrent\u2122 sequencing of DNA extracted from four normal colonic segments (two left-sided and two right) of patients with SHiGDAs. We also contrasted unique mutational fields in one patient with a large HiGDA (APC with unique mutations) and one patient who prospectively developed a SHiGDA (JAK3). Result: The SHiGDA (small high-grade dysplastic polyp) patient was p87 negative for any extracted stool, saliva, or colonic effluent via ELISA (enzyme linked immunoadsorbant assay). Furthermore, mean values of expression in segments from the right colon were reduced with respect to the means obtained from the left segments in 233 patients evaluated for a p87 field effect. This has recently been shown to be the case in a large cohort of AA and Caucasian 2294 patients, possibly explaining the right-sided CRC disparity in African Americans and the subsequent increase in mortality. This field effect disparity is also true for two cancers contracted by the SHiGDa patient (lung and prostate). Conclusion: Thus, this pilot study suggests that the reduction in p87 in the right colon is possibly correlated with JAK3 mutations. If confirmed, JAK3 mutations, known to be associated with immune aberrations, may provide a mechanistic explanation for the lack of a p87 (protein 87 kilodaltons) field in some patients with HGD polyps who might benefit from possible intervention such as more intensive screening. Limited microbiome studies were also performed on two patients with familial cancer syndromes and these compared favorably with controls available from the literature.<\/jats:p>","DOI":"10.3390\/gidisord6020034","type":"journal-article","created":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T11:56:48Z","timestamp":1717761408000},"page":"497-512","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Innate Immune System Surveillance Biomarker p87 in African Americans and Caucasians with Small High-Grade Dysplastic Adenoma [SHiGDA] and Right-Sided JAK3 Colon Mutations May Explain the Presence of Multiple Cancers Revealing an Important Minority of Patients with JAK3 Mutations and Colorectal Neoplasia"],"prefix":"10.3390","volume":"6","author":[{"given":"Martin","family":"Tobi","sequence":"first","affiliation":[{"name":"Department of Research and Development, Detroit John D. Dingle VAMC, Detroit, MI 48201, USA"},{"name":"Central Michigan University, Saginaw Campus, 1632 Stone St., Saginaw, MI 48602, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoqing","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Research and Development, Detroit John D. Dingle VAMC, Detroit, MI 48201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Rodriquez","sequence":"additional","affiliation":[{"name":"Philadelphia VAMC, 3900 Woodland Avenue, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0781-7681","authenticated-orcid":false,"given":"Yosef Y.","family":"Tobi","sequence":"additional","affiliation":[{"name":"Department of Research and Development, Detroit John D. Dingle VAMC, Detroit, MI 48201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tapan","family":"Ganguly","sequence":"additional","affiliation":[{"name":"Department of Genetics, Perelman School of Medicine, Clinical Research Building 500, 415 Curie Blvd., University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donald","family":"Kuhn","sequence":"additional","affiliation":[{"name":"Department of Research and Development Service, Detroit VAMC, 4646 John R., Detroit, MI 48201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7876-149X","authenticated-orcid":false,"given":"Benita","family":"McVicker","sequence":"additional","affiliation":[{"name":"Research Service, VA Nebraska-Western Iowa Health Care System, The University of Nebraska Medical Center, Omaha, NE 68105, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Lawson","sequence":"additional","affiliation":[{"name":"Department Gastroenterology, University of California, Davis Sacramento, 3160 Folsom Blvd., Suite 3500, Sacramento, CA 95816, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"II","given":"John","family":"Lieb","sequence":"additional","affiliation":[{"name":"Divisions of Gastroenterology, Hepatology and Nutrition, University of Florida at Gainesville, Gainesville VAMC, 1601 Southwest Archer Road, Gainesville, FL 32608, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9795-1093","authenticated-orcid":false,"given":"Jaime L.","family":"Lopes","sequence":"additional","affiliation":[{"name":"Cincinnati Children\u2019s Hospital, Division of Genetics, Department of Pediatrics, University of Cincinnati, 3333 Burnet Ave., Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1053\/j.gastro.2008.02.002","article-title":"Screening and Surveillance for the Early Detection of Colorectal Cancer and Adenomatous Polyps, 2008: A Joint Guideline From the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology","volume":"134","author":"Levin","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Tobi, M., Antaki, F., Rambus, M.A., Yang, Y.-X., Kaplan, D., Rodriguez, R., Maliakkal, B., Majumdar, A., Demian, E., and Tobi, Y.Y. (2023). The Non-Invasive Prediction of Colorectal Neoplasia (NIPCON) Study 1995\u20132022: A Comparison of Guaiac-Based Fecal Occult Blood Test (FOBT) and an Anti-Adenoma Antibody, Adnab-9. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242417257"},{"key":"ref_3","first-page":"1547","article-title":"Effect of Colonoscopy Screening on Risks of Colorectal Cancer and Related Death. New Engl","volume":"387","author":"Bretthauer","year":"2022","journal-title":"J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1053\/j.gastro.2012.06.001","article-title":"Guidelines for Colonoscopy Surveillance After Screening and Polypectomy: A Consensus Update by the US Multi-Society Task Force on Colorectal Cancer","volume":"143","author":"Lieberman","year":"2012","journal-title":"Gastroenterology"},{"key":"ref_5","first-page":"434","article-title":"Coloretal cancer screening: Practices and attitudes of gastroenterologists, internists and surgeons","volume":"48","author":"Hilsden","year":"2006","journal-title":"Can. J. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2366","DOI":"10.1001\/jama.295.20.2366","article-title":"Risk of Developing Colorectal Cancer Following a Negative Colonoscopy Examination","volume":"295","author":"Singh","year":"2006","journal-title":"Jama"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7326\/0003-4819-150-1-200901060-00306","article-title":"Association of colonoscopy and death from colorectal cancer","volume":"150","author":"Baxter","year":"2009","journal-title":"Ann. Intern. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1093\/jnci\/djp436","article-title":"Protection from Right- and Left-Sided Colorectal Neoplasms After Colonoscopy: Population-Based Study","volume":"102","author":"Brenner","year":"2010","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e185","DOI":"10.1038\/ctg.2016.36","article-title":"Colorectal Cancer in African Americans: An Update","volume":"7","author":"Williams","year":"2016","journal-title":"Clin. Transl. Gastroenterol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1002\/1097-0142(19890901)64:5<1138::AID-CNCR2820640529>3.0.CO;2-A","article-title":"Early colorectal carcinoma with special reference to its development de novo","volume":"64","author":"Shimoda","year":"1989","journal-title":"Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2664","DOI":"10.1200\/JCO.2011.40.4772","article-title":"Association Between Colonoscopy and Colorectal Cancer Mortality in a US Cohort According to Site of Cancer and Colonoscopist Specialty","volume":"30","author":"Baxter","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1053\/j.gastro.2005.06.012","article-title":"AGA Future trends committee report: CRC: A Qualitative review of emerging screening and diagnostic technologies","volume":"129","author":"Regueiro","year":"2005","journal-title":"Gastroenterology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1053\/j.gastro.2008.12.007","article-title":"A Pooled Analysis of Advanced Colorectal Neoplasia Diagnoses After Colonoscopic Polypectomy","volume":"136","author":"Baron","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1038\/ajg.2010.423","article-title":"The ACG Emily Couric Lecture- The adenoma-carcinoma sequence revisited: Has the era of genetic tailoring finally arrived?","volume":"106","author":"Ahnen","year":"2011","journal-title":"Am. J. Gastroenterol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"22","DOI":"10.7326\/0003-4819-154-1-201101040-00004","article-title":"Protection from Colorectal Cancer After Colonoscopy: A Population-Based, Case\u2013Control Study","volume":"154","author":"Brenner","year":"2011","journal-title":"Ann. Intern. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/S1542-3565(04)00012-6","article-title":"Small early tubular adenomas and mixed colonic polyps found on screening flexible sigmoidoscopy do not predict proximal neoplasia in males","volume":"2","author":"Ullah","year":"2004","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2242","DOI":"10.1111\/j.1572-0241.2004.40131.x","article-title":"Hyperplastic polyps, serrated adenomas, and the serrated polyp neoplasia pathway","volume":"99","author":"Huang","year":"2004","journal-title":"Am. J. Gastroenterol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1097\/01.pas.0000213313.36306.85","article-title":"Comparison of Microsatellite Instability, CpG Island Methylation Phenotype, BRAF and KRAS Status in Serrated Polyps and Traditional Adenomas Indicates Separate Pathways to Distinct Colorectal Carcinoma End Points","volume":"30","author":"Yang","year":"2006","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.gtc.2007.12.014","article-title":"Sporadic and syndromic hyperplastic polyps and serrated adenomas of the colon: Classification, molecular genetics, natural history, and clinical management","volume":"37","author":"East","year":"2008","journal-title":"Gastroenterol. Clin. N. Am."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1038\/nm0995-902","article-title":"Microallelotyping defines the sequence and tempo of allelic losses at tumour suppressor gene loci during colorectal cancer progression","volume":"9","author":"Boland","year":"1995","journal-title":"Nat. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1038\/s41418-020-00672-0","article-title":"Identification and functional characterization of new missense SNPs in the coding region of the TP53 gene","volume":"28","author":"Doffe","year":"2020","journal-title":"Cell Death Differ."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1007\/s10620-014-3443-5","article-title":"Screening for Colorectal Cancer in African Americans: Determinants and Rationale for an Earlier Age to Commence Screening","volume":"60","author":"Carethers","year":"2014","journal-title":"Dig. Dis. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40246-024-00603-x","article-title":"Altered skin microbiome, inflammation, and JAK\/STAT signaling in Southeast Asian ichthyosis patients","volume":"18","author":"Ho","year":"2024","journal-title":"Hum. Genom."},{"key":"ref_24","first-page":"1","article-title":"The JAK\/STAT signaling pathway: From bench to clinic","volume":"6","author":"Hu","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.chom.2020.03.005","article-title":"Structure of the Mucosal and Stool Microbiome in Lynch Syndrome","volume":"27","author":"Yan","year":"2020","journal-title":"Cell Host Microbe"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e32194","DOI":"10.1097\/MD.0000000000032194","article-title":"How is gut microbiome of patients with familial adenomatous polyposis different from healthy people?","volume":"101","author":"Kim","year":"2022","journal-title":"Medicine"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1023\/A:1013713920805","article-title":"Colorectal cancer risk: The impact of evidence of a field effect of carcinogenesis on blinded diagnosis using an anti-adenoma antibody test performed on colonoscopic effluent","volume":"47","author":"Tobi","year":"2002","journal-title":"Dig. Dis. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.canlet.2005.03.042","article-title":"Fecal Adnab-9 binding as a risk marker for colorectal neoplasia","volume":"235","author":"Yuan","year":"2006","journal-title":"Cancer Lett."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1023\/A:1021727608133","article-title":"Correlation of Ki-67, p53, and Adnab-9 immunohistochemical staining and ploidy with clinical and histopathologic features of severely dysplastic colorectal adenomas. Dig","volume":"48","author":"Sheikh","year":"2003","journal-title":"Dis. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1038\/onc.2015.150","article-title":"Targeting JAK kinase in solid tumors: Emerging opportunities and challenges","volume":"35","author":"Buchert","year":"2016","journal-title":"Oncogene"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1007\/BF02234324","article-title":"Molecular markers are predictors of recurrence and survival in patients with Dukes B and Dukes C colorectal adenocarcinoma","volume":"44","author":"Bhatavdekar","year":"2001","journal-title":"Dis. Colon. Rectum."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1385\/IJGC:29:3:141","article-title":"Prognostic Significance of the Labeling of Adnab-9 in Pancreatic Intraductal Papillary Mucinous Neoplasms","volume":"29","author":"Tobi","year":"2001","journal-title":"J. Gastrointest. Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1007\/s10620-012-2387-x","article-title":"Prospective Markers for Early Diagnosis and Prognosis of Sporadic Pancreatic Ductal Adenocarcinoma","volume":"58","author":"Tobi","year":"2012","journal-title":"Dig. Dis. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1056\/NEJMp1600448","article-title":"Colorectal Cancer on the Decline Why Screening Can\u2019t Explain It All","volume":"374","author":"Welch","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"587","DOI":"10.3892\/ijo.2014.2469","article-title":"Differential expression of miRNAs in colon cancer between African and Caucasian Americans: Implications for cancer racial health disparities","volume":"45","author":"Li","year":"2014","journal-title":"Int. J. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1158\/1541-7786.MCR-13-0286-T","article-title":"Transcriptomes and shRNA Suppressors in a TP53 Allele specific Model of Early-onset Colon Cancer in African Americans","volume":"12","author":"Weige","year":"2014","journal-title":"Mol. Cancer Res."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Kuracha, M.R., Govindarajan, V., Loggie, B.W., Tobi, M., and McVicker, B.L. (2023). Pictilisib-Induced Resistance Is Mediated through FOXO1-Dependent Activation of Receptor Tyrosine Kinases in Mucinous Colorectal Adenocarcinoma Cells. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241512331"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Jovov, B., Araujo-Perez, F., Sigel, C.S., Stratford, J.K., McCoy, A.N., Yeh, J.J., and Keku, T. (2012). Differential Gene Expression between African American and European American Colorectal Cancer Patients. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0030168"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1593\/neo.81006","article-title":"Blocking of p53-Snail binding, promoted by oncogenic K-Ras, recovers p53 expression and function","volume":"11","author":"Lee","year":"2009","journal-title":"Neoplasia"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1002\/oby.20702","article-title":"BMI and the risk of colorectal adenoma in African-Americans","volume":"22","author":"Ashktorab","year":"2014","journal-title":"Obesity"},{"key":"ref_41","first-page":"320","article-title":"Effect of Targeting Janus Kinase 3 on the Development of Intestinal Tumors in the Adenomatous Polyposis Colimin Mouse Model of Familial Adenomatous Polyposis","volume":"57","author":"Uckun","year":"2007","journal-title":"Arzneimittelforschung"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1158\/1535-7163.MCT-21-0943","article-title":"Low-Dose JAK3 Inhibition Improves Antitumor T-Cell Immunity and Immunotherapy Efficacy","volume":"21","author":"Dammeijer","year":"2022","journal-title":"Mol. Cancer Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"440","DOI":"10.2174\/1871520622666220609112816","article-title":"Novel Potent EGFR-JAK3 Dual-Target Inhibitor that Overcomes KRAS Mutation Resistance in Colorectal Cancer","volume":"23","author":"Chen","year":"2023","journal-title":"Anti-Cancer Agents Med. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1097\/00000478-200312000-00008","article-title":"Analysis of Protein Expression and Gene Mutation of c-kit in Colorectal Neuroendocrine Carcinomas","volume":"27","author":"Pfeifer","year":"2003","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1111\/ajco.12603","article-title":"Prognostic significance of KITexon 11 deletion mutation in intermediate-risk gastrointestinal stromal tumor","volume":"13","author":"Quek","year":"2016","journal-title":"Asia-Pacific J. Clin. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/s00253-015-6978-2","article-title":"Targeting c-kit receptor in neuroblastomas and colorectal cancers using stem cell factor (SCF)-based recombinant bacterial toxins","volume":"100","author":"Choudhary","year":"2016","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_47","first-page":"1","article-title":"KIT promotes tumor stroma formation and counteracts tumor-suppressive TGF\u03b2 signaling in colorectal cancer","volume":"13","author":"Peters","year":"2022","journal-title":"Cell Death Dis."}],"container-title":["Gastrointestinal Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2624-5647\/6\/2\/34\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:55:24Z","timestamp":1760108124000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2624-5647\/6\/2\/34"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,7]]},"references-count":47,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["gidisord6020034"],"URL":"https:\/\/doi.org\/10.3390\/gidisord6020034","relation":{},"ISSN":["2624-5647"],"issn-type":[{"type":"electronic","value":"2624-5647"}],"subject":[],"published":{"date-parts":[[2024,6,7]]}}}