The role of biomarkers to increase the detection of early-onset colorectal cancer
Main Article Content
Abstract
Colorectal cancer is the third most diagnosed cancer worldwide with an estimated 1.93 million cases diagnosed in 2020. Over the past few decades there has been a dramatic rise in the incidence of early onset colorectal cancer, defined as colorectal cancer diagnosed in those aged under 50 years. The largest predictor of survival is early stage at diagnosis, therefore ways to improve prompt diagnosis of early onset colorectal cancer at an early stage is an effective way of managing the impact of this rising disease. Diagnosing colorectal cancer in younger patients has unique challenges with patients falling outside the age of most screening programs and early symptoms of colorectal cancer being common, non-specific and initially intermittent.
While colonoscopy remains the gold standard investigation, it is a limited and expensive resource, and current patterns of practice result in large numbers of patients being scoped unnecessarily. The development and use of new and novel non-invasive biomarkers may help (either alone or in combination) identify either symptomatic patients in primary care, or aid with screening asymptomatic patients to focus resources where they are needed most. This review discusses challenges around diagnosing early onset colorectal cancer, with an overview of both current and future methods that might help overcome these challenges. These include increased assessment of familial risk, and the measurement of different biomarkers including faecal haemoglobin, markers of inflammation, gut microbiota, and selected metabolites.
Keywords:
early-onset colorectal cancer, diagnosis, biomarkers, screening.
Article Details
How to Cite
WADDELL, Oliver; FRIZELLE, Frank A.; KEENAN, Jacqueline I..
The role of biomarkers to increase the detection of early-onset colorectal cancer.
Medical Research Archives, [S.l.], v. 11, n. 11, nov. 2023.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/4690>. Date accessed: 16 may 2024.
doi: https://doi.org/10.18103/mra.v11i11.4690.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Ferlay J, Colombet M, Soerjomataram I, et al. Cancer statistics for the year 2020: An overview. Int J Cancer. 2021;149(4):778-789. doi:10.1002/IJC.33588
2. Chittleborough TJ, Gutlic I, Pearson JF, et al. Increasing incidence of young-onset colorectal carcinoma A 3-country population analysis. Dis Colon Rectum. 2020;63(7):903-910. doi:10.1097/DCR.0000000000001631
3. Siegel RL, Wagle NS, Cercek A, Smith RA, Jemal A. Colorectal cancer statistics, 2023. CA Cancer J Clin. Published online May 2023. doi:10.3322/CAAC.21772
3. Bailey CE, Hu CY, You YN, et al. Increasing disparities in age-related incidence of colon and rectal cancer in the United States, 1975-2010. JAMA Surg. 2015;150(1)
doi:10.1001/ jamasurg.2014.1756.
4. Zaborowski AM, Abdile A, Adamina M, et al. Characteristics of Early-Onset vs Late-Onset Colorectal Cancer. JAMA Surg. 2021;156(9):865-874. doi:10.1001/jamasurg.2021.2380
5. Keenan JI, Frizelle FA. Toxigenic gut bacteria, diet and colon carcinogenesis. J R Soc N Z. 2020;50(3):418-433.
doi:10.1080/03036758.2019.1695636
6. Carr PR, Weigl K, Jansen L, et al. Healthy Lifestyle Factors Associated With Lower Risk of Colorectal Cancer Irrespective of Genetic Risk. Gastroenterology. 2018;155(6):1805-1815.e5. doi:10.1053/J.GASTRO.2018.08.044
8. Sinicrope FA. Increasing Incidence of Early-Onset Colorectal Cancer. New England Journal of Medicine. 2022;386(16):1547-1558. doi:10.1056/nejmra2200869
9. Scott RB, Rangel LE, Osler TM, Hyman NH. Rectal cancer in patients under the age of 50 years: the delayed diagnosis. The American Journal of Surgery. 2016;211(6):1014-1018. doi:10.1016/J.AMJSURG.2015.08.031
10. Abdelsattar ZM, Wong SL, Regenbogen SE, Jomaa DM, Hardiman KM, Hendren S. Colorectal cancer outcomes and treatment patterns in patients too young for average-risk screening. Cancer. 2016;122(6):929-934. doi:10.1002/CNCR.29716
11. Levin B, Lieberman DA, McFarland B, et al. 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. CA Cancer J Clin. 2008;58(3):130-160. doi:10.3322/CA.2007.0018
12. Gupta S, Bharti B, Ahnen DJ, et al. Potential impact of family history-based screening guidelines on the detection of early-onset colorectal cancer. Cancer. 2020;126(13):3013-3020. doi:10.1002/CNCR.32851
13. Sifri RD, Wender R, Paynter N, Philadelphia BS. Cancer risk assessment from family history: Gaps in primary care practice. Journal of family practice. 2002;51(10).
14. Sassano M, Mariani M, Quaranta G, Pastorino R, Boccia S. Polygenic risk prediction models for colorectal cancer: a systematic review. BMC Cancer. 2022;22(1). doi:10.1186/S12885-021-09143-2
15. Fritz CDL, Otegbeye EE, Zong X, et al. Red-flag signs and symptoms for earlier diagnosis of early-onset colorectal cancer. JNCI: Journal of the National Cancer Institute. 2023;115(8):909-916. doi:10.1093/JNCI/DJAD068
16. Yen T, Patel SG. Symptoms and early-onset colorectal cancer: red flags are common flags! J Natl Cancer Inst. 2023;115(8). doi:10.1093/JNCI/DJAD093
17. Loktionov A. Biomarkers for detecting colorectal cancer non-invasively: DNA, RNA or proteins? World J Gastrointest Oncol. 2020;12(2):124-148. doi:10.4251/WJGO.V12.I2.124
18. Keenan JI, Frizelle FA. Biomarkers to Detect Early-Stage Colorectal Cancer. Biomedicines. 2022;10(2).
doi:10.3390/BIOMEDICINES10020255
19. Srivastava S, Koay EJ, Borowsky AD, et al. Cancer overdiagnosis: a biological challenge and clinical dilemma. Nat Rev Cancer. 2019;19(6):349-358.
doi:10.1038/S41568-019-0142-8
20. Farshidfar F, Kopciuk KA, Hilsden R, et al. A quantitative multimodal metabolomic assay for colorectal cancer. BMC Cancer. 2018;18(1). doi:10.1186/S12885-017-3923-Z
21. Keenan JI, Aitchison A, Frizelle FA, Hock BD. Detection of Chitinase 3-Like 1 in Symptomatic Primary Care Patient Faecal Samples is Not a Reliable Biomarker of Colonic Lesions. Asian Pac J Cancer Prev. 2023;24(7):2289-2293. doi:10.31557/APJCP.2023.24.7.2289
22. Widlak MM, Thomas CL, Thomas MG, et al. Diagnostic accuracy of faecal biomarkers in detecting colorectal cancer and adenoma in symptomatic patients. Aliment Pharmacol Ther. 2017;45(2):354-363. doi:10.1111/APT.13865
23. Loktionov A, Soubieres A, Bandaletova T, et al. Biomarker measurement in non-invasively sampled colorectal mucus as a novel approach to colorectal cancer detection: screening and triage implications. Br J Cancer. 2020;123(2):252-260. doi:10.1038/S41416-020-0893-8
24. Patel NR, McPhail MJW, Shariff MIF, Keun HC, Taylor-Robinson SD. Biofluid metabonomics using (1)H NMR spectroscopy: the road to biomarker discovery in gastroenterology and hepatology. Expert Rev Gastroenterol Hepatol. 2012;6(2):239-251.
doi:10.1586/EGH.12.1
25. Garcia-Perez I, Posma JM, Gibson R, et al. Objective assessment of dietary patterns by use of metabolic phenotyping: a randomised, controlled, crossover trial. Lancet Diabetes Endocrinol. 2017;5(3):184-195.
doi:10.1016/S2213-8587(16)30419-3
26. Issaq HJ, Waybright TJ, Veenstra TD. Cancer biomarker discovery: Opportunities and pitfalls in analytical methods. Electrophoresis. 2011;32(9):967-975.
doi:10.1002/ELPS.201000588
27. Young GP, Symonds EL, Allison JE, et al. Advances in Fecal Occult Blood Tests: the FIT revolution. Dig Dis Sci. 2015;60(3):609-622. doi:10.1007/S10620-014-3445-3
28. Fraser CG. Interpretation of faecal haemoglobin concentration data in colorectal cancer screening and in assessment of symptomatic patients. J Lab Precis Med. 2017;2(12):96-96. doi:10.21037/JLPM.2017.11.01
29. Godber IM, Todd LM, Fraser CG, MacDonald LR, Younes H Ben. Use of a faecal immunochemical test for haemoglobin can aid in the investigation of patients with lower abdominal symptoms. Clin Chem Lab Med. 2016;54(4):595-602.
doi:10.1515/CCLM-2015-0617
30. Mowat C, Digby J, Strachan JA, et al. Faecal haemoglobin and faecal calprotectin as indicators of bowel disease in patients presenting to primary care with bowel symptoms. Gut. 2016;65(9):1463-1469.
doi:10.1136/GUTJNL-2015-309579
31. Widlak MM, Neal M, Daulton E, et al. Risk stratification of symptomatic patients suspected of colorectal cancer using faecal and urinary markers. Colorectal Dis. 2018;20(12):O335-O342. doi:10.1111/CODI.14431
32. Mowat C, Digby J, Strachan JA, et al. Impact of introducing a faecal immunochemical test (FIT) for haemoglobin into primary care on the outcome of patients with new bowel symptoms: a prospective cohort study. BMJ Open Gastroenterol. 2019;6(1).
doi:10.1136/BMJGAST-2019-000293
33. Navarro M, Hijos G, Ramirez T, Omella I, Fuentes PC Las, Lanas A. Fecal Hemoglobin Concentration, a Good Predictor of Risk of Advanced Colorectal Neoplasia in Symptomatic and Asymptomatic Patients. Front Med (Lausanne). 2019;6(APR):91. doi:10.3389/FMED.2019.00091
34. Nicholson BD, James T, Paddon M, et al. Faecal immunochemical testing for adults with symptoms of colorectal cancer attending English primary care: a retrospective cohort study of 14 487 consecutive test requests. Aliment Pharmacol Ther. 2020;52(6):1031-1041. doi:10.1111/APT.15969
35. Souza DD’. GI cancer Faecal immunochemical test is superior to symptoms in predicting pathology in patients with suspected colorectal cancer symptoms referred on a 2WW pathway: a diagnostic accuracy study The NICE FIT Steering Group. Gut. 2020;0:1-9. doi:10.1136/gutjnl-2020-321956
36. MacDonald S, MacDonald L, Godwin J, Macdonald A, Thornton M. The diagnostic accuracy of the faecal immunohistochemical test in identifying significant bowel disease in a symptomatic population. Colorectal Dis. 2022;24(3):257-263. doi:10.1111/CODI.15994
37. National Institute for Health and Care Excellence (NICE). NICE. Quantitative faecal immunochemical tests to guide referral for colorectal cancer in primary care [DG30]. Published online 2017.
38. Chapman C, Bunce J, Oliver S, et al. Service evaluation of faecal immunochemical testing and anaemia for risk stratification in the 2‐week‐wait pathway for colorectal cancer. BJS Open. 2019;3(3):395.
doi:10.1002/BJS5.50131
39. Cross AJ, Wooldrage K, Robbins EC, et al. Whole-colon investigation vs. flexible sigmoidoscopy for suspected colorectal cancer based on presenting symptoms and signs: a multicentre cohort study. British Journal of Cancer 2018;120(2):154-164.
doi:10.1038/s41416-018-0335-z
40. D’Souza N, Monahan K, Benton SC, et al. Finding the needle in the haystack: the diagnostic accuracy of the faecal immunochemical test for colorectal cancer in younger symptomatic patients. Colorectal Dis. 2021;23(10):2539-2549.
doi:10.1111/CODI.15786
41. Hicks G, D’Souza N, Georgiou Delisle T, Chen M, Benton SC, Abulafi M. Using the faecal immunochemical test in patients with rectal bleeding: evidence from the NICE FIT study. Colorectal Disease. 2021;23(7):1630-1638. doi:10.1111/CODI.15593
42. D’Souza N, Delisle TG, Chen M, et al. Faecal immunochemical testing in symptomatic patients to prioritize investigation: diagnostic accuracy from NICE FIT Study. British Journal of Surgery. 2021;108(7):804-810.
doi:10.1093/BJS/ZNAA132
43. Barnett KN, Clark GRC, Steele RJC, Fraser CG. Faecal Haemoglobin Estimated by Faecal Immunochemical Tests—An Indicator of Systemic Inflammation with Real Clinical Potential. Diagnostics 2021;11(11):2093.
doi:10.3390/DIAGNOSTICS11112093
44. Keenan J, Aitchison A, Leaman J, Pearson J, Frizelle F. Faecal biomarkers do not always identify pre-cancerous lesions in patients who present in primary care with bowel symptoms. N Z Med J. 2019;132(1501):48-56. Accessed September 20, 2023.
https://pubmed.ncbi.nlm.nih.gov/31465327/
45. Røseth AG, Kristinsson J, Fagerhol MK, et al. Faecal calprotectin: a novel test for the diagnosis of colorectal cancer? Scand J Gastroenterol. 1993;28(12):1073-1076.
doi:10.3109/00365529309098312
46. Tibble J, Sigthorsson G, Foster R, Sherwood R, Fagerhol M, Bjarnason I. Faecal calprotectin and faecal occult blood tests in the diagnosis of colorectal carcinoma and adenoma. Gut. 2001;49(3):402.
doi:10.1136/GUT.49.3.402
47. Summerton CB, Longlands MG, Wiener K, Shreeve DR. Faecal calprotectin: a marker of inflammation throughout the intestinal tract. Eur J Gastroenterol Hepatol.
2002;14(8):841-845.
doi:10.1097/00042737-200208000-00005
48. Kan YM, Chu SY, Loo CK. Diagnostic accuracy of fecal calprotectin in predicting significant gastrointestinal diseases. JGH Open.
2021;5(6):647. doi:10.1002/JGH3.12548
49. Johansen JS, Christensen IJ, Jørgensen LN, et al. Serum YKL-40 in risk assessment for colorectal cancer: a prospective study of 4,496 subjects at risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev. 2015;24(3):621-626.
doi:10.1158/1055-9965.EPI-13-1281
50. Mizoguchi E. Chitinase 3-like-1 exacerbates intestinal inflammation by enhancing bacterial adhesion and invasion in colonic epithelial cells. Gastroenterology. 2006;130(2):398-411. doi:10.1053/J.GASTRO.2005.12.007
51. Turvill J, Aghahoseini A, Sivarajasingham N, et al. Faecal calprotectin in patients with suspected colorectal cancer: a diagnostic accuracy study. The British Journal of General Practice. 2016;66(648):e499.
doi:10.3399/BJGP16X685645
52. Lué A, Hijos G, Sostres C, et al. The combination of quantitative faecal occult blood test and faecal calprotectin is a cost-effective strategy to avoid colonoscopies in symptomatic patients without relevant pathology. Therap Adv Gastroenterol. 2020;13. doi:10.1177/1756284820920786
53. National Institute of Health Care and Excellence (NICE). NICE Suspected cancer: recognition and referral [NG12]. Suspected cancer: recognition and referral. Published online December 15, 2015. Accessed September 20, 2023.
https://www.ncbi.nlm.nih.gov/books/NBK555330/
54. Chuter C, Keding A, Holmes H, Turnock D, Turvill J. Getting the best out of faecal immunochemical tests and faecal calprotectin. Frontline Gastroenterol. 2020;11(5):414.
doi:10.1136/FLGASTRO-2019-101381
55. Sears CL. Enterotoxigenic Bacteroides fragilis: a rogue among symbiotes. Clin Microbiol Rev. 2009;22(2):349-369.
doi:10.1128/CMR.00053-08
56. Rhee KJ, Wu S, Wu X, et al. Induction of persistent colitis by a human commensal, enterotoxigenic Bacteroides fragilis, in wild-type C57BL/6 mice. Infect Immun. 2009;77(4): 1708-1718. doi:10.1128/IAI.00814-08
57. Purcell R V, Pearson J, Aitchison A, Dixon L, Frizelle FA, Keenan JI. Colonization with enterotoxigenic Bacteroides fragilis is associated with early-stage colorectal neoplasia. PLoS One. 2017 Feb 2;12(2):e0171602.
doi:10.1371/journal.pone.0171602
58. Ulger Toprak N, Yagci A, Gulluoglu BM, et al. A possible role of Bacteroides fragilis enterotoxin in the aetiology of colorectal cancer. Clin Microbiol Infect. 2006;12(8):782-786. doi:10.1111/J.1469-0691.2006.01494.X
59. Keenan JI, Aitchison A, Purcell R V., Greenlees R, Pearson JF, Frizelle FA. Screening for enterotoxigenic Bacteroides fragilis in stool samples. Anaerobe. 2016;40:50-53. doi:10.1016/J.ANAEROBE.2016.05.004
60. Tjalsma H, Boleij A, Marchesi JR, Dutilh BE. A bacterial driver-passenger model for colorectal cancer: beyond the usual suspects. Nat Rev Microbiol. 2012;10(8):575-582.
doi:10.1038/NRMICRO2819
61. Garza DR, Taddese R, Wirbel J, et al. Metabolic models predict bacterial passengers in colorectal cancer. Cancer Metab. 2020;8(1). doi:10.1186/S40170-020-0208-9
62. Shen XJ, Rawls JF, Randall T, et al. Molecular characterization of mucosal adherent bacteria and associations with colorectal adenomas. Gut Microbes. 2010;1(3):138. doi:10.4161/GMIC.1.3.12360
63. Hale VL, Chen J, Johnson S, et al. Shifts in the Fecal Microbiota Associated with Adenomatous Polyps. Cancer Epidemiol Biomarkers Prev. 2017;26(1):85-94.
doi:10.1158/1055-9965.EPI-16-0337
64. Feng Q, Liang S, Jia H, et al. Gut microbiome development along the colorectal adenoma-carcinoma sequence. Nat Commun. 2015;6. doi:10.1038/NCOMMS7528
65. Nakatsu G, Li X, Zhou H, et al. Gut mucosal microbiome across stages of colorectal carcinogenesis. Nat Commun. 2015;6. doi:10.1038/NCOMMS9727
66. Weir TL, Manter DK, Sheflin AM, Barnett BA, Heuberger AL, Ryan EP. Stool microbiome and metabolome differences between colorectal cancer patients and healthy adults. PLoS One. 2013;8(8). doi:10.1371/JOURNAL.PONE.0070803
67. Wishart DS. Is Cancer a Genetic Disease or a Metabolic Disease? EBioMedicine. 2015;2(6):478. doi:10.1016/J.EBIOM.2015.05.022
68. Chan ECY, Koh PK, Mal M, et al. Metabolic profiling of human colorectal cancer using high-resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy and gas chromatography mass spectrometry (GC/MS). J Proteome Res. 2009;8(1):352-361. doi:10.1021/PR8006232/ASSET/IMAGES/LARGE/PR-2008-006232_0003.JPEG
69. Sonoda H, Kohnoe S, Yamazato T, et al. Colorectal cancer screening with odour material by canine scent detection. Gut.
2011;60(6):814-819. doi:10.1136/GUT.2010.218305
70. Altomare DF, Di Lena M, Porcelli F, et al. Exhaled volatile organic compounds identify patients with colorectal cancer. British Journal of Surgery. 2012;100(1):144-150.
doi:10.1002/BJS.8942
71. Wang C, Ke C, Wang X, et al. Noninvasive detection of colorectal cancer by analysis of exhaled breath. Anal Bioanal Chem. 2014;406(19):4757-4763. doi:10.1007/S00216-014-7865-X
72. Amal H, Leja M, Funka K, et al. Breath testing as potential colorectal cancer screening tool. Int J Cancer. 2016;138(1):229-236.
doi:10.1002/IJC.29701
73. Arasaradnam RP, Mcfarlane MJ, Ryan-Fisher C, et al. Detection of Colorectal Cancer (CRC) by Urinary Volatile Organic Compound Analysis. PLoS One. 2014;9(9):e108750. doi:10.1371/JOURNAL.PONE.0108750
74. Westenbrink E, Arasaradnam RP, O’Connell N, et al. Development and application of a new electronic nose instrument for the detection of colorectal cancer. Biosens Bioelectron. 2015;67:733-738.
doi:10.1016/J.BIOS.2014.10.044
75. Wang C, Li P, Lian A, et al. Blood volatile compounds as biomarkers for colorectal cancer. Cancer Biol Ther. 2014;15(2):200-206. doi:10.4161/CBT.26723
76. De Meij TG, Larbi I Ben, Van Der Schee MP, et al. Electronic nose can discriminate colorectal carcinoma and advanced adenomas by fecal volatile biomarker analysis: proof of principle study. Int J Cancer.
2014;134(5):1132-1138. doi:10.1002/IJC.28446
77. Batty CA, Cauchi M, Lourenço C, Hunter JO, Turner C. Use of the Analysis of the Volatile Faecal Metabolome in Screening for Colorectal Cancer. PLoS One.
2015;10(6):e0130301. doi:10.1371/JOURNAL.PONE.0130301
78. Ishibe A, Ota M, Takeshita A, et al. Detection of gas components as a novel diagnostic method for colorectal cancer. Ann Gastroenterol Surg. 2018;2(2):147.
doi:10.1002/AGS3.12056
79. Bond A, Greenwood R, Lewis S, et al. Volatile organic compounds emitted from faeces as a biomarker for colorectal cancer. Aliment Pharmacol Ther. 2019;49(8):1005-1012. doi:10.1111/APT.15140
80. Erben V, Bhardwaj M, Schrotz-King P, Brenner H. Metabolomics Biomarkers for Detection of Colorectal Neoplasms: A Systematic Review. Cancers (Basel). 2018;10(8). doi:10.3390/CANCERS10080246
81. Roager HM, Hansen LBS, Bahl MI, et al. Colonic transit time is related to bacterial metabolism and mucosal turnover in the gut. Nature Microbiology 2016 1:9. 2016;1(9):1-9. doi:10.1038/nmicrobiol.2016.93
82. Cross AJ, Boca S, Freedman ND, et al. Metabolites of tobacco smoking and colorectal cancer risk. Carcinogenesis. 2014;35(7):1516. doi:10.1093/CARCIN/BGU071
83. Thévenot EA, Roux A, Xu Y, Ezan E, Junot C. Analysis of the Human Adult Urinary Metabolome Variations with Age, Body Mass Index, and Gender by Implementing a Comprehensive Workflow for Univariate and OPLS Statistical Analyses. J Proteome Res. 2015;14(8):3322-3335. doi:10.1021/ACS.JPROTEOME.5B00354
84. Mallafré‐muro C, Llambrich M, Cumeras R, et al. Comprehensive volatilome and metabolome signatures of colorectal cancer in urine: A systematic review and meta‐analysis. Cancers (Basel). 2021;13(11):2534.
doi:10.3390/CANCERS13112534/S1
85. Farshidfar F, Weljie AM, Kopciuk KA, et al. A validated metabolomic signature for colorectal cancer: exploration of the clinical value of metabolomics. Br J Cancer. 2016;115
(7):848-857. doi:10.1038/BJC.2016.243
86. Uchiyama K, Yagi N, Mizushima K, et al. Serum metabolomics analysis for early detection of colorectal cancer. J Gastroenterol.
2017;52(6):677-694.
doi:10.1007/S00535-016-1261-6
87. van Keulen KE, Jansen ME, Schrauwen RWM, Kolkman JJ, Siersema PD. Volatile organic compounds in breath can serve as a non-invasive diagnostic biomarker for the detection of advanced adenomas and colorectal cancer. Aliment Pharmacol Ther. 2020;51(3):334-346. doi:10.1111/APT.15622
88. Zheng X, Hur J, Nguyen LH, et al. Comprehensive Assessment of Diet Quality and Risk of Precursors of Early-Onset Colorectal Cancer. J Natl Cancer Inst. 2021 May 4;113(5):543-552.
doi:10.1093/jnci/djaa164
89. Louis P, Hold GL, Flint HJ. The gut microbiota, bacterial metabolites and colorectal cancer. Nat Rev Microbiol. 2014;12(10):661-672. doi:10.1038/NRMICRO3344
90. Cipolla BG, Havouis R, Moulinoux JP. Polyamine contents in current foods: a basis for polyamine reduced diet and a study of its long term observance and tolerance in prostate carcinoma patients. Amino Acids. 2007;33(2):203-212.
doi:10.1007/S00726-007-0524-1
91. Pegg AE. Toxicity of polyamines and their metabolic products. Chem Res Toxicol. 2013; 26(12):1782-1800. doi:10.1021/TX400316S
92. Battaglia V, DeStefano Shields C, Murray-Stewart T, Casero RA. Polyamine catabolism in carcinogenesis: Potential targets for chemotherapy and chemoprevention. Amino Acids. 2014;46(3):511-519.
doi:10.1007/S00726-013-1529-6/FIGURES/2
93. Wang Y, Hacker A, Murray-Stewart T, Fleischer JG, Woster PM, Casero RA. Induction of human spermine oxidase SMO(PAOh1) is regulated at the levels of new mRNA synthesis, mRNA stabilization and newly synthesized protein. Biochemical Journal. 2005;386(Pt 3):543.
doi:10.1042/BJ20041084
94. Goodwin AC, Destefano Shields CE, Wu S, et al. Polyamine catabolism contributes to enterotoxigenic Bacteroides fragilis-induced colon tumorigenesis. Proc Natl Acad Sci U S A. 2011;108(37):15354-15359.
doi:10.1073/PNAS.1010203108
95. Hiramatsu K, Takahashi K, Yamaguchi T, et al. N1,N12-Diacetylspermine as a Sensitive and Specific Novel Marker for Early- and Late-Stage Colorectal and Breast Cancers. Clinical Cancer Research. 2005;11(8):2986-2990.
doi:10.1158/1078-0432.CCR-04-2275
96. Zeevi D, Korem T, Zmora N, et al. Personalized Nutrition by Prediction of Glycemic Responses. Cell. 2015;163(5):1079-1094. doi:10.1016/j.cell.2015.11.001
97. Vulcan A, Manjer J, Ohlsson B. High blood glucose levels are associated with higher risk of colon cancer in men: a cohort study. BMC Cancer. 2017;17(1).
doi:10.1186/S12885-017-3874-4
98. Yu X, Chen C, Song X, et al. Glycosylated Hemoglobin as an Age-Specific Predictor and Risk Marker of Colorectal Adenomas in Non-Diabetic Adults. Front Endocrinol (Lausanne). 2021;12:1. doi:10.3389/FENDO.2021.774519
99. Yuan C, Joh HK, Wang QL, et al. Sugar-sweetened beverage and sugar consumption and colorectal cancer incidence and mortality according to anatomic subsite. Am J Clin Nutr. 2022;115(6):1481-1489.
doi:10.1093/AJCN/NQAC040
100. Hur J, Otegbeye E, Joh HK, et al. Sugar-sweetened beverage intake in adulthood and adolescence and risk of early-onset colorectal cancer among women. Gut.
2021;70(12):2330-2336.
doi:10.1136/gutjnl-2020-323450
101. Sieri S, Agnoli C, Pala V, et al. Dietary glycemic index, glycemic load, and cancer risk: results from the EPIC-Italy study. Sci Rep. 2017;7(1). doi:10.1038/S41598-017-09498-2
102. Korpela K. Diet, Microbiota, and Metabolic Health: Trade-Off Between Saccharolytic and Proteolytic Fermentation. Annu Rev Food Sci Technol. 2018;9:65-84. doi:10.1146/ANNUREV-FOOD-030117012830
103. Laffin M, Fedorak R, Zalasky A, et al. A high-sugar diet rapidly enhances susceptibility to colitis via depletion of luminal short-chain fatty acids in mice. Scientific Reports 2019 9:1. 2019;9(1):1-11.
doi:10.1038/s41598-019-48749-2
104. Overbeeke A, Lang M, Hausmann B, et al. Impaired Mucosal Homeostasis in Short-Term Fiber Deprivation Is Due to Reduced Mucus Production Rather Than Overgrowth of Mucus-Degrading Bacteria. Nutrients. 2022;14(18). doi:10.3390/NU14183802
105. Zahra K, Dey T, Ashish, Mishra SP, Pandey U. Pyruvate Kinase M2 and Cancer: The Role of PKM2 in Promoting Tumorigenesis. Front Oncol. 2020;10:505842. doi:10.3389/FONC.2020.00159/BIBTEX
106. Schreuders EH, Ruco A, Rabeneck L, et al. Colorectal cancer screening: a global overview of existing programmes. Gut. 2015;64(10):1637-1649. doi:10.1136/GUTJNL-2014-309086
107. Patel SG, May FP, Anderson JC, et al. Updates on Age to Start and Stop Colorectal Cancer Screening: Recommendations From the U.S. Multi-Society Task Force on Colorectal Cancer. Gastroenterology. 2022;162(1):285-299. doi:10.1053/j.gastro.2021.10.007
108. Knudsen AB, Rutter CM, Peterse EFP, et al. Colorectal Cancer Screening: An Updated Decision Analysis for the U.S. Preventive Services Task Force. Colorectal Cancer Screening: An Updated Decision Analysis for the US Preventive Services Task Force. 2021;(AHRQ Publication No. 20-05271-EF-2). Accessed September 13, 2022.
https://www.ncbi.nlm.nih.gov/books/NBK570833/
109. De Klaver W, Wisse PHA, Van Wifferen F, et al. Clinical Validation of a Multitarget Fecal Immunochemical Test for Colorectal Cancer Screening. Ann Intern Med. 2021;174(9):1224-1231. doi:10.7326/M20-8270
2. Chittleborough TJ, Gutlic I, Pearson JF, et al. Increasing incidence of young-onset colorectal carcinoma A 3-country population analysis. Dis Colon Rectum. 2020;63(7):903-910. doi:10.1097/DCR.0000000000001631
3. Siegel RL, Wagle NS, Cercek A, Smith RA, Jemal A. Colorectal cancer statistics, 2023. CA Cancer J Clin. Published online May 2023. doi:10.3322/CAAC.21772
3. Bailey CE, Hu CY, You YN, et al. Increasing disparities in age-related incidence of colon and rectal cancer in the United States, 1975-2010. JAMA Surg. 2015;150(1)
doi:10.1001/ jamasurg.2014.1756.
4. Zaborowski AM, Abdile A, Adamina M, et al. Characteristics of Early-Onset vs Late-Onset Colorectal Cancer. JAMA Surg. 2021;156(9):865-874. doi:10.1001/jamasurg.2021.2380
5. Keenan JI, Frizelle FA. Toxigenic gut bacteria, diet and colon carcinogenesis. J R Soc N Z. 2020;50(3):418-433.
doi:10.1080/03036758.2019.1695636
6. Carr PR, Weigl K, Jansen L, et al. Healthy Lifestyle Factors Associated With Lower Risk of Colorectal Cancer Irrespective of Genetic Risk. Gastroenterology. 2018;155(6):1805-1815.e5. doi:10.1053/J.GASTRO.2018.08.044
8. Sinicrope FA. Increasing Incidence of Early-Onset Colorectal Cancer. New England Journal of Medicine. 2022;386(16):1547-1558. doi:10.1056/nejmra2200869
9. Scott RB, Rangel LE, Osler TM, Hyman NH. Rectal cancer in patients under the age of 50 years: the delayed diagnosis. The American Journal of Surgery. 2016;211(6):1014-1018. doi:10.1016/J.AMJSURG.2015.08.031
10. Abdelsattar ZM, Wong SL, Regenbogen SE, Jomaa DM, Hardiman KM, Hendren S. Colorectal cancer outcomes and treatment patterns in patients too young for average-risk screening. Cancer. 2016;122(6):929-934. doi:10.1002/CNCR.29716
11. Levin B, Lieberman DA, McFarland B, et al. 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. CA Cancer J Clin. 2008;58(3):130-160. doi:10.3322/CA.2007.0018
12. Gupta S, Bharti B, Ahnen DJ, et al. Potential impact of family history-based screening guidelines on the detection of early-onset colorectal cancer. Cancer. 2020;126(13):3013-3020. doi:10.1002/CNCR.32851
13. Sifri RD, Wender R, Paynter N, Philadelphia BS. Cancer risk assessment from family history: Gaps in primary care practice. Journal of family practice. 2002;51(10).
14. Sassano M, Mariani M, Quaranta G, Pastorino R, Boccia S. Polygenic risk prediction models for colorectal cancer: a systematic review. BMC Cancer. 2022;22(1). doi:10.1186/S12885-021-09143-2
15. Fritz CDL, Otegbeye EE, Zong X, et al. Red-flag signs and symptoms for earlier diagnosis of early-onset colorectal cancer. JNCI: Journal of the National Cancer Institute. 2023;115(8):909-916. doi:10.1093/JNCI/DJAD068
16. Yen T, Patel SG. Symptoms and early-onset colorectal cancer: red flags are common flags! J Natl Cancer Inst. 2023;115(8). doi:10.1093/JNCI/DJAD093
17. Loktionov A. Biomarkers for detecting colorectal cancer non-invasively: DNA, RNA or proteins? World J Gastrointest Oncol. 2020;12(2):124-148. doi:10.4251/WJGO.V12.I2.124
18. Keenan JI, Frizelle FA. Biomarkers to Detect Early-Stage Colorectal Cancer. Biomedicines. 2022;10(2).
doi:10.3390/BIOMEDICINES10020255
19. Srivastava S, Koay EJ, Borowsky AD, et al. Cancer overdiagnosis: a biological challenge and clinical dilemma. Nat Rev Cancer. 2019;19(6):349-358.
doi:10.1038/S41568-019-0142-8
20. Farshidfar F, Kopciuk KA, Hilsden R, et al. A quantitative multimodal metabolomic assay for colorectal cancer. BMC Cancer. 2018;18(1). doi:10.1186/S12885-017-3923-Z
21. Keenan JI, Aitchison A, Frizelle FA, Hock BD. Detection of Chitinase 3-Like 1 in Symptomatic Primary Care Patient Faecal Samples is Not a Reliable Biomarker of Colonic Lesions. Asian Pac J Cancer Prev. 2023;24(7):2289-2293. doi:10.31557/APJCP.2023.24.7.2289
22. Widlak MM, Thomas CL, Thomas MG, et al. Diagnostic accuracy of faecal biomarkers in detecting colorectal cancer and adenoma in symptomatic patients. Aliment Pharmacol Ther. 2017;45(2):354-363. doi:10.1111/APT.13865
23. Loktionov A, Soubieres A, Bandaletova T, et al. Biomarker measurement in non-invasively sampled colorectal mucus as a novel approach to colorectal cancer detection: screening and triage implications. Br J Cancer. 2020;123(2):252-260. doi:10.1038/S41416-020-0893-8
24. Patel NR, McPhail MJW, Shariff MIF, Keun HC, Taylor-Robinson SD. Biofluid metabonomics using (1)H NMR spectroscopy: the road to biomarker discovery in gastroenterology and hepatology. Expert Rev Gastroenterol Hepatol. 2012;6(2):239-251.
doi:10.1586/EGH.12.1
25. Garcia-Perez I, Posma JM, Gibson R, et al. Objective assessment of dietary patterns by use of metabolic phenotyping: a randomised, controlled, crossover trial. Lancet Diabetes Endocrinol. 2017;5(3):184-195.
doi:10.1016/S2213-8587(16)30419-3
26. Issaq HJ, Waybright TJ, Veenstra TD. Cancer biomarker discovery: Opportunities and pitfalls in analytical methods. Electrophoresis. 2011;32(9):967-975.
doi:10.1002/ELPS.201000588
27. Young GP, Symonds EL, Allison JE, et al. Advances in Fecal Occult Blood Tests: the FIT revolution. Dig Dis Sci. 2015;60(3):609-622. doi:10.1007/S10620-014-3445-3
28. Fraser CG. Interpretation of faecal haemoglobin concentration data in colorectal cancer screening and in assessment of symptomatic patients. J Lab Precis Med. 2017;2(12):96-96. doi:10.21037/JLPM.2017.11.01
29. Godber IM, Todd LM, Fraser CG, MacDonald LR, Younes H Ben. Use of a faecal immunochemical test for haemoglobin can aid in the investigation of patients with lower abdominal symptoms. Clin Chem Lab Med. 2016;54(4):595-602.
doi:10.1515/CCLM-2015-0617
30. Mowat C, Digby J, Strachan JA, et al. Faecal haemoglobin and faecal calprotectin as indicators of bowel disease in patients presenting to primary care with bowel symptoms. Gut. 2016;65(9):1463-1469.
doi:10.1136/GUTJNL-2015-309579
31. Widlak MM, Neal M, Daulton E, et al. Risk stratification of symptomatic patients suspected of colorectal cancer using faecal and urinary markers. Colorectal Dis. 2018;20(12):O335-O342. doi:10.1111/CODI.14431
32. Mowat C, Digby J, Strachan JA, et al. Impact of introducing a faecal immunochemical test (FIT) for haemoglobin into primary care on the outcome of patients with new bowel symptoms: a prospective cohort study. BMJ Open Gastroenterol. 2019;6(1).
doi:10.1136/BMJGAST-2019-000293
33. Navarro M, Hijos G, Ramirez T, Omella I, Fuentes PC Las, Lanas A. Fecal Hemoglobin Concentration, a Good Predictor of Risk of Advanced Colorectal Neoplasia in Symptomatic and Asymptomatic Patients. Front Med (Lausanne). 2019;6(APR):91. doi:10.3389/FMED.2019.00091
34. Nicholson BD, James T, Paddon M, et al. Faecal immunochemical testing for adults with symptoms of colorectal cancer attending English primary care: a retrospective cohort study of 14 487 consecutive test requests. Aliment Pharmacol Ther. 2020;52(6):1031-1041. doi:10.1111/APT.15969
35. Souza DD’. GI cancer Faecal immunochemical test is superior to symptoms in predicting pathology in patients with suspected colorectal cancer symptoms referred on a 2WW pathway: a diagnostic accuracy study The NICE FIT Steering Group. Gut. 2020;0:1-9. doi:10.1136/gutjnl-2020-321956
36. MacDonald S, MacDonald L, Godwin J, Macdonald A, Thornton M. The diagnostic accuracy of the faecal immunohistochemical test in identifying significant bowel disease in a symptomatic population. Colorectal Dis. 2022;24(3):257-263. doi:10.1111/CODI.15994
37. National Institute for Health and Care Excellence (NICE). NICE. Quantitative faecal immunochemical tests to guide referral for colorectal cancer in primary care [DG30]. Published online 2017.
38. Chapman C, Bunce J, Oliver S, et al. Service evaluation of faecal immunochemical testing and anaemia for risk stratification in the 2‐week‐wait pathway for colorectal cancer. BJS Open. 2019;3(3):395.
doi:10.1002/BJS5.50131
39. Cross AJ, Wooldrage K, Robbins EC, et al. Whole-colon investigation vs. flexible sigmoidoscopy for suspected colorectal cancer based on presenting symptoms and signs: a multicentre cohort study. British Journal of Cancer 2018;120(2):154-164.
doi:10.1038/s41416-018-0335-z
40. D’Souza N, Monahan K, Benton SC, et al. Finding the needle in the haystack: the diagnostic accuracy of the faecal immunochemical test for colorectal cancer in younger symptomatic patients. Colorectal Dis. 2021;23(10):2539-2549.
doi:10.1111/CODI.15786
41. Hicks G, D’Souza N, Georgiou Delisle T, Chen M, Benton SC, Abulafi M. Using the faecal immunochemical test in patients with rectal bleeding: evidence from the NICE FIT study. Colorectal Disease. 2021;23(7):1630-1638. doi:10.1111/CODI.15593
42. D’Souza N, Delisle TG, Chen M, et al. Faecal immunochemical testing in symptomatic patients to prioritize investigation: diagnostic accuracy from NICE FIT Study. British Journal of Surgery. 2021;108(7):804-810.
doi:10.1093/BJS/ZNAA132
43. Barnett KN, Clark GRC, Steele RJC, Fraser CG. Faecal Haemoglobin Estimated by Faecal Immunochemical Tests—An Indicator of Systemic Inflammation with Real Clinical Potential. Diagnostics 2021;11(11):2093.
doi:10.3390/DIAGNOSTICS11112093
44. Keenan J, Aitchison A, Leaman J, Pearson J, Frizelle F. Faecal biomarkers do not always identify pre-cancerous lesions in patients who present in primary care with bowel symptoms. N Z Med J. 2019;132(1501):48-56. Accessed September 20, 2023.
https://pubmed.ncbi.nlm.nih.gov/31465327/
45. Røseth AG, Kristinsson J, Fagerhol MK, et al. Faecal calprotectin: a novel test for the diagnosis of colorectal cancer? Scand J Gastroenterol. 1993;28(12):1073-1076.
doi:10.3109/00365529309098312
46. Tibble J, Sigthorsson G, Foster R, Sherwood R, Fagerhol M, Bjarnason I. Faecal calprotectin and faecal occult blood tests in the diagnosis of colorectal carcinoma and adenoma. Gut. 2001;49(3):402.
doi:10.1136/GUT.49.3.402
47. Summerton CB, Longlands MG, Wiener K, Shreeve DR. Faecal calprotectin: a marker of inflammation throughout the intestinal tract. Eur J Gastroenterol Hepatol.
2002;14(8):841-845.
doi:10.1097/00042737-200208000-00005
48. Kan YM, Chu SY, Loo CK. Diagnostic accuracy of fecal calprotectin in predicting significant gastrointestinal diseases. JGH Open.
2021;5(6):647. doi:10.1002/JGH3.12548
49. Johansen JS, Christensen IJ, Jørgensen LN, et al. Serum YKL-40 in risk assessment for colorectal cancer: a prospective study of 4,496 subjects at risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev. 2015;24(3):621-626.
doi:10.1158/1055-9965.EPI-13-1281
50. Mizoguchi E. Chitinase 3-like-1 exacerbates intestinal inflammation by enhancing bacterial adhesion and invasion in colonic epithelial cells. Gastroenterology. 2006;130(2):398-411. doi:10.1053/J.GASTRO.2005.12.007
51. Turvill J, Aghahoseini A, Sivarajasingham N, et al. Faecal calprotectin in patients with suspected colorectal cancer: a diagnostic accuracy study. The British Journal of General Practice. 2016;66(648):e499.
doi:10.3399/BJGP16X685645
52. Lué A, Hijos G, Sostres C, et al. The combination of quantitative faecal occult blood test and faecal calprotectin is a cost-effective strategy to avoid colonoscopies in symptomatic patients without relevant pathology. Therap Adv Gastroenterol. 2020;13. doi:10.1177/1756284820920786
53. National Institute of Health Care and Excellence (NICE). NICE Suspected cancer: recognition and referral [NG12]. Suspected cancer: recognition and referral. Published online December 15, 2015. Accessed September 20, 2023.
https://www.ncbi.nlm.nih.gov/books/NBK555330/
54. Chuter C, Keding A, Holmes H, Turnock D, Turvill J. Getting the best out of faecal immunochemical tests and faecal calprotectin. Frontline Gastroenterol. 2020;11(5):414.
doi:10.1136/FLGASTRO-2019-101381
55. Sears CL. Enterotoxigenic Bacteroides fragilis: a rogue among symbiotes. Clin Microbiol Rev. 2009;22(2):349-369.
doi:10.1128/CMR.00053-08
56. Rhee KJ, Wu S, Wu X, et al. Induction of persistent colitis by a human commensal, enterotoxigenic Bacteroides fragilis, in wild-type C57BL/6 mice. Infect Immun. 2009;77(4): 1708-1718. doi:10.1128/IAI.00814-08
57. Purcell R V, Pearson J, Aitchison A, Dixon L, Frizelle FA, Keenan JI. Colonization with enterotoxigenic Bacteroides fragilis is associated with early-stage colorectal neoplasia. PLoS One. 2017 Feb 2;12(2):e0171602.
doi:10.1371/journal.pone.0171602
58. Ulger Toprak N, Yagci A, Gulluoglu BM, et al. A possible role of Bacteroides fragilis enterotoxin in the aetiology of colorectal cancer. Clin Microbiol Infect. 2006;12(8):782-786. doi:10.1111/J.1469-0691.2006.01494.X
59. Keenan JI, Aitchison A, Purcell R V., Greenlees R, Pearson JF, Frizelle FA. Screening for enterotoxigenic Bacteroides fragilis in stool samples. Anaerobe. 2016;40:50-53. doi:10.1016/J.ANAEROBE.2016.05.004
60. Tjalsma H, Boleij A, Marchesi JR, Dutilh BE. A bacterial driver-passenger model for colorectal cancer: beyond the usual suspects. Nat Rev Microbiol. 2012;10(8):575-582.
doi:10.1038/NRMICRO2819
61. Garza DR, Taddese R, Wirbel J, et al. Metabolic models predict bacterial passengers in colorectal cancer. Cancer Metab. 2020;8(1). doi:10.1186/S40170-020-0208-9
62. Shen XJ, Rawls JF, Randall T, et al. Molecular characterization of mucosal adherent bacteria and associations with colorectal adenomas. Gut Microbes. 2010;1(3):138. doi:10.4161/GMIC.1.3.12360
63. Hale VL, Chen J, Johnson S, et al. Shifts in the Fecal Microbiota Associated with Adenomatous Polyps. Cancer Epidemiol Biomarkers Prev. 2017;26(1):85-94.
doi:10.1158/1055-9965.EPI-16-0337
64. Feng Q, Liang S, Jia H, et al. Gut microbiome development along the colorectal adenoma-carcinoma sequence. Nat Commun. 2015;6. doi:10.1038/NCOMMS7528
65. Nakatsu G, Li X, Zhou H, et al. Gut mucosal microbiome across stages of colorectal carcinogenesis. Nat Commun. 2015;6. doi:10.1038/NCOMMS9727
66. Weir TL, Manter DK, Sheflin AM, Barnett BA, Heuberger AL, Ryan EP. Stool microbiome and metabolome differences between colorectal cancer patients and healthy adults. PLoS One. 2013;8(8). doi:10.1371/JOURNAL.PONE.0070803
67. Wishart DS. Is Cancer a Genetic Disease or a Metabolic Disease? EBioMedicine. 2015;2(6):478. doi:10.1016/J.EBIOM.2015.05.022
68. Chan ECY, Koh PK, Mal M, et al. Metabolic profiling of human colorectal cancer using high-resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy and gas chromatography mass spectrometry (GC/MS). J Proteome Res. 2009;8(1):352-361. doi:10.1021/PR8006232/ASSET/IMAGES/LARGE/PR-2008-006232_0003.JPEG
69. Sonoda H, Kohnoe S, Yamazato T, et al. Colorectal cancer screening with odour material by canine scent detection. Gut.
2011;60(6):814-819. doi:10.1136/GUT.2010.218305
70. Altomare DF, Di Lena M, Porcelli F, et al. Exhaled volatile organic compounds identify patients with colorectal cancer. British Journal of Surgery. 2012;100(1):144-150.
doi:10.1002/BJS.8942
71. Wang C, Ke C, Wang X, et al. Noninvasive detection of colorectal cancer by analysis of exhaled breath. Anal Bioanal Chem. 2014;406(19):4757-4763. doi:10.1007/S00216-014-7865-X
72. Amal H, Leja M, Funka K, et al. Breath testing as potential colorectal cancer screening tool. Int J Cancer. 2016;138(1):229-236.
doi:10.1002/IJC.29701
73. Arasaradnam RP, Mcfarlane MJ, Ryan-Fisher C, et al. Detection of Colorectal Cancer (CRC) by Urinary Volatile Organic Compound Analysis. PLoS One. 2014;9(9):e108750. doi:10.1371/JOURNAL.PONE.0108750
74. Westenbrink E, Arasaradnam RP, O’Connell N, et al. Development and application of a new electronic nose instrument for the detection of colorectal cancer. Biosens Bioelectron. 2015;67:733-738.
doi:10.1016/J.BIOS.2014.10.044
75. Wang C, Li P, Lian A, et al. Blood volatile compounds as biomarkers for colorectal cancer. Cancer Biol Ther. 2014;15(2):200-206. doi:10.4161/CBT.26723
76. De Meij TG, Larbi I Ben, Van Der Schee MP, et al. Electronic nose can discriminate colorectal carcinoma and advanced adenomas by fecal volatile biomarker analysis: proof of principle study. Int J Cancer.
2014;134(5):1132-1138. doi:10.1002/IJC.28446
77. Batty CA, Cauchi M, Lourenço C, Hunter JO, Turner C. Use of the Analysis of the Volatile Faecal Metabolome in Screening for Colorectal Cancer. PLoS One.
2015;10(6):e0130301. doi:10.1371/JOURNAL.PONE.0130301
78. Ishibe A, Ota M, Takeshita A, et al. Detection of gas components as a novel diagnostic method for colorectal cancer. Ann Gastroenterol Surg. 2018;2(2):147.
doi:10.1002/AGS3.12056
79. Bond A, Greenwood R, Lewis S, et al. Volatile organic compounds emitted from faeces as a biomarker for colorectal cancer. Aliment Pharmacol Ther. 2019;49(8):1005-1012. doi:10.1111/APT.15140
80. Erben V, Bhardwaj M, Schrotz-King P, Brenner H. Metabolomics Biomarkers for Detection of Colorectal Neoplasms: A Systematic Review. Cancers (Basel). 2018;10(8). doi:10.3390/CANCERS10080246
81. Roager HM, Hansen LBS, Bahl MI, et al. Colonic transit time is related to bacterial metabolism and mucosal turnover in the gut. Nature Microbiology 2016 1:9. 2016;1(9):1-9. doi:10.1038/nmicrobiol.2016.93
82. Cross AJ, Boca S, Freedman ND, et al. Metabolites of tobacco smoking and colorectal cancer risk. Carcinogenesis. 2014;35(7):1516. doi:10.1093/CARCIN/BGU071
83. Thévenot EA, Roux A, Xu Y, Ezan E, Junot C. Analysis of the Human Adult Urinary Metabolome Variations with Age, Body Mass Index, and Gender by Implementing a Comprehensive Workflow for Univariate and OPLS Statistical Analyses. J Proteome Res. 2015;14(8):3322-3335. doi:10.1021/ACS.JPROTEOME.5B00354
84. Mallafré‐muro C, Llambrich M, Cumeras R, et al. Comprehensive volatilome and metabolome signatures of colorectal cancer in urine: A systematic review and meta‐analysis. Cancers (Basel). 2021;13(11):2534.
doi:10.3390/CANCERS13112534/S1
85. Farshidfar F, Weljie AM, Kopciuk KA, et al. A validated metabolomic signature for colorectal cancer: exploration of the clinical value of metabolomics. Br J Cancer. 2016;115
(7):848-857. doi:10.1038/BJC.2016.243
86. Uchiyama K, Yagi N, Mizushima K, et al. Serum metabolomics analysis for early detection of colorectal cancer. J Gastroenterol.
2017;52(6):677-694.
doi:10.1007/S00535-016-1261-6
87. van Keulen KE, Jansen ME, Schrauwen RWM, Kolkman JJ, Siersema PD. Volatile organic compounds in breath can serve as a non-invasive diagnostic biomarker for the detection of advanced adenomas and colorectal cancer. Aliment Pharmacol Ther. 2020;51(3):334-346. doi:10.1111/APT.15622
88. Zheng X, Hur J, Nguyen LH, et al. Comprehensive Assessment of Diet Quality and Risk of Precursors of Early-Onset Colorectal Cancer. J Natl Cancer Inst. 2021 May 4;113(5):543-552.
doi:10.1093/jnci/djaa164
89. Louis P, Hold GL, Flint HJ. The gut microbiota, bacterial metabolites and colorectal cancer. Nat Rev Microbiol. 2014;12(10):661-672. doi:10.1038/NRMICRO3344
90. Cipolla BG, Havouis R, Moulinoux JP. Polyamine contents in current foods: a basis for polyamine reduced diet and a study of its long term observance and tolerance in prostate carcinoma patients. Amino Acids. 2007;33(2):203-212.
doi:10.1007/S00726-007-0524-1
91. Pegg AE. Toxicity of polyamines and their metabolic products. Chem Res Toxicol. 2013; 26(12):1782-1800. doi:10.1021/TX400316S
92. Battaglia V, DeStefano Shields C, Murray-Stewart T, Casero RA. Polyamine catabolism in carcinogenesis: Potential targets for chemotherapy and chemoprevention. Amino Acids. 2014;46(3):511-519.
doi:10.1007/S00726-013-1529-6/FIGURES/2
93. Wang Y, Hacker A, Murray-Stewart T, Fleischer JG, Woster PM, Casero RA. Induction of human spermine oxidase SMO(PAOh1) is regulated at the levels of new mRNA synthesis, mRNA stabilization and newly synthesized protein. Biochemical Journal. 2005;386(Pt 3):543.
doi:10.1042/BJ20041084
94. Goodwin AC, Destefano Shields CE, Wu S, et al. Polyamine catabolism contributes to enterotoxigenic Bacteroides fragilis-induced colon tumorigenesis. Proc Natl Acad Sci U S A. 2011;108(37):15354-15359.
doi:10.1073/PNAS.1010203108
95. Hiramatsu K, Takahashi K, Yamaguchi T, et al. N1,N12-Diacetylspermine as a Sensitive and Specific Novel Marker for Early- and Late-Stage Colorectal and Breast Cancers. Clinical Cancer Research. 2005;11(8):2986-2990.
doi:10.1158/1078-0432.CCR-04-2275
96. Zeevi D, Korem T, Zmora N, et al. Personalized Nutrition by Prediction of Glycemic Responses. Cell. 2015;163(5):1079-1094. doi:10.1016/j.cell.2015.11.001
97. Vulcan A, Manjer J, Ohlsson B. High blood glucose levels are associated with higher risk of colon cancer in men: a cohort study. BMC Cancer. 2017;17(1).
doi:10.1186/S12885-017-3874-4
98. Yu X, Chen C, Song X, et al. Glycosylated Hemoglobin as an Age-Specific Predictor and Risk Marker of Colorectal Adenomas in Non-Diabetic Adults. Front Endocrinol (Lausanne). 2021;12:1. doi:10.3389/FENDO.2021.774519
99. Yuan C, Joh HK, Wang QL, et al. Sugar-sweetened beverage and sugar consumption and colorectal cancer incidence and mortality according to anatomic subsite. Am J Clin Nutr. 2022;115(6):1481-1489.
doi:10.1093/AJCN/NQAC040
100. Hur J, Otegbeye E, Joh HK, et al. Sugar-sweetened beverage intake in adulthood and adolescence and risk of early-onset colorectal cancer among women. Gut.
2021;70(12):2330-2336.
doi:10.1136/gutjnl-2020-323450
101. Sieri S, Agnoli C, Pala V, et al. Dietary glycemic index, glycemic load, and cancer risk: results from the EPIC-Italy study. Sci Rep. 2017;7(1). doi:10.1038/S41598-017-09498-2
102. Korpela K. Diet, Microbiota, and Metabolic Health: Trade-Off Between Saccharolytic and Proteolytic Fermentation. Annu Rev Food Sci Technol. 2018;9:65-84. doi:10.1146/ANNUREV-FOOD-030117012830
103. Laffin M, Fedorak R, Zalasky A, et al. A high-sugar diet rapidly enhances susceptibility to colitis via depletion of luminal short-chain fatty acids in mice. Scientific Reports 2019 9:1. 2019;9(1):1-11.
doi:10.1038/s41598-019-48749-2
104. Overbeeke A, Lang M, Hausmann B, et al. Impaired Mucosal Homeostasis in Short-Term Fiber Deprivation Is Due to Reduced Mucus Production Rather Than Overgrowth of Mucus-Degrading Bacteria. Nutrients. 2022;14(18). doi:10.3390/NU14183802
105. Zahra K, Dey T, Ashish, Mishra SP, Pandey U. Pyruvate Kinase M2 and Cancer: The Role of PKM2 in Promoting Tumorigenesis. Front Oncol. 2020;10:505842. doi:10.3389/FONC.2020.00159/BIBTEX
106. Schreuders EH, Ruco A, Rabeneck L, et al. Colorectal cancer screening: a global overview of existing programmes. Gut. 2015;64(10):1637-1649. doi:10.1136/GUTJNL-2014-309086
107. Patel SG, May FP, Anderson JC, et al. Updates on Age to Start and Stop Colorectal Cancer Screening: Recommendations From the U.S. Multi-Society Task Force on Colorectal Cancer. Gastroenterology. 2022;162(1):285-299. doi:10.1053/j.gastro.2021.10.007
108. Knudsen AB, Rutter CM, Peterse EFP, et al. Colorectal Cancer Screening: An Updated Decision Analysis for the U.S. Preventive Services Task Force. Colorectal Cancer Screening: An Updated Decision Analysis for the US Preventive Services Task Force. 2021;(AHRQ Publication No. 20-05271-EF-2). Accessed September 13, 2022.
https://www.ncbi.nlm.nih.gov/books/NBK570833/
109. De Klaver W, Wisse PHA, Van Wifferen F, et al. Clinical Validation of a Multitarget Fecal Immunochemical Test for Colorectal Cancer Screening. Ann Intern Med. 2021;174(9):1224-1231. doi:10.7326/M20-8270