1.Bray, F, Ferlay, J, Soerjomataram, I, et al. (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68, 394–424.
2.World Cancer Research Fund/American Institute for Cancer Research (2018) Continuous Update Project Expert Report. Diet, Nutrition, Physical Activity and Cancer: a Global Perspective. London: World Cancer Research Fund International.
3.Rock, CL, Doyle, C, Demark-Wahnefried, W, et al. (2012) Nutrition and physical activity guidelines for cancer survivors. CA Cancer J Clin 62, 243–274.
4.Ulrich, CM, Himbert, C, Holowatyj, AN, et al. (2018) Energy balance and gastrointestinal cancer: risk, interventions, outcomes and mechanisms. Nat Rev Gastroenterol Hepatol 15, 683–698.
5.van Zutphen, M, Kampman, E, Giovannucci, EL, et al. (2017) Lifestyle after colorectal cancer diagnosis in relation to survival and recurrence: a review of the literature. Curr Colorectal Cancer Rep 13, 370–401.
6.Ait Ouakrim, D, Pizot, C, Boniol, M, et al. (2015) Trends in colorectal cancer mortality in Europe: retrospective analysis of the WHO mortality database. BMJ 351, h4970.
7.Drew, DA, Cao, Y & Chan, AT (2016) Aspirin and colorectal cancer: the promise of precision chemoprevention. Nat Rev Cancer 16, 173–186.
8.Ullman, TA & Itzkowitz, SH (2011) Intestinal inflammation and cancer. Gastroenterology 140, 1807–1816.
9.Ulrich, CM, Bigler, J & Potter, JD (2006) Non-steroidal anti-inflammatory drugs for cancer prevention: promise, perils and pharmacogenetics. Nat Rev Cancer 6, 130–140.
10.Toriola, AT & Ulrich, CM (2011) Is there a potential use for C-reactive protein as a diagnostic and prognostic marker for colorectal cancer? Future Oncol 7, 1125–1128.
11.Landskron, G, De la Fuente, M, Thuwajit, P, et al. (2014) Chronic inflammation and cytokines in the tumor microenvironment. J Immunol Res 2014, 19.
12.Albini, A, Bruno, A, Noonan, DM, et al. (2018) Contribution to tumor angiogenesis from innate immune cells within the tumor microenvironment: implications for immunotherapy. Front Immunol 9, 527.
13.Tonini, T, Rossi, F & Claudio, PP (2003) Molecular basis of angiogenesis and cancer. Oncogene 22, 6549.
14.Locasale, JW (2013) Serine, glycine and one-carbon units: cancer metabolism in full circle. Nat Rev Cancer 13, 572.
15.Abbenhardt, C, Miller, JW, Song, X, et al. (2014) Biomarkers of one-carbon metabolism are associated with biomarkers of inflammation in women. J Nutr 144, 714–721.
16.Mayne, ST, Ferrucci, LM & Cartmel, B (2012) Lessons learned from randomized clinical trials of micronutrient supplementation for cancer prevention. Annu Rev Nutr 32, 369–390.
17.Lochhead, P, Nishihara, R, Qian, ZR, et al. (2015) Postdiagnostic intake of one-carbon nutrients and alcohol in relation to colorectal cancer survival. Am J Clin Nutr 102, 1134–1141.
18.Zschabitz, S, Cheng, TY, Neuhouser, ML, et al. (2013) B vitamin intakes and incidence of colorectal cancer: results from the Women’s Health Initiative Observational Study cohort. Am J Clin Nutr 97, 332–343.
19.Friso, S, Jacques, PF, Wilson, PW, et al. (2001) Low circulating vitamin B(6) is associated with elevation of the inflammation marker C-reactive protein independently of plasma homocysteine levels. Circulation 103, 2788–2791.
20.Shen, J, Lai, CQ, Mattei, J, et al. (2010) Association of vitamin B-6 status with inflammation, oxidative stress, and chronic inflammatory conditions: the Boston Puerto Rican Health Study. Am J Clin Nutr 91, 337–342.
21.Gigic, B, Boeing, H, Toth, R, et al. (2018) Associations between dietary patterns and longitudinal quality of life changes in colorectal cancer patients: the ColoCare Study. Nutr Cancer 70, 51–60.
22.Liesenfeld, DB, Grapov, D, Fahrmann, JF, et al. (2015) Metabolomics and transcriptomics identify pathway differences between visceral and subcutaneous adipose tissue in colorectal cancer patients: the ColoCare study. Am J Clin Nutr 102, 433–443.
23.Ulrich, CM, Gigic, B, Böhm, J, et al. (2018) The ColoCare Study - A paradigm of transdisciplinary science in colorectal cancer outcomes. Cancer Epidemiol Biomarkers Prev 28, 591–601.
24.Gryfe, R (2009) Inherited colorectal cancer syndromes. Clin Colon Rectal Surg 22, 198–208.
25.Labayle, D, Fischer, D, Vielh, P, et al. (1991) Sulindac causes regression of rectal polyps in familial adenomatous polyposis. Gastroenterology 101, 635–639.
26.Burn, J, Gerdes, AM, Macrae, F, et al. (2011) Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial. Lancet 378, 2081–2087.
27.Himbert, C, Ose, J, Nattenmüller, J, et al. (2019) Body fatness, adipose tissue compartments, and biomarkers of inflammation and angiogenesis in colorectal cancer: the ColoCare Study. Cancer Epidemiol Biomarkers Prev 28, 76–82.
28.Midttun, O, Kvalheim, G & Ueland, PM (2013) High-throughput, low-volume, multianalyte quantification of plasma metabolites related to one-carbon metabolism using HPLC-MS/MS. Anal Bioanal Chem 405, 2009–2017.
29.Institute of Medicine (2006) Dietary Reference Intakes, The Essential Guide to Nutrient Requirements. Washington, DC: National Academies Press.
30.Ueland, PM, McCann, A, Midttun, Ø, et al. (2017) Inflammation, vitamin B6 and related pathways. Mol Aspects Med 53, 10–27.
31.Ulvik, A, Midttun, O, Pedersen, ER, et al. (2014) Evidence for increased catabolism of vitamin B-6 during systemic inflammation. Am J Clin Nutr 100, 250–255.
32.Ulvik, A, Theofylaktopoulou, D, Midttun, O, et al. (2013) Substrate product ratios of enzymes in the kynurenine pathway measured in plasma as indicators of functional vitamin B-6 status. Am J Clin Nutr 98, 934–940.
33.Krumsiek, J, Suhre, K, Illig, T, et al. (2011) Gaussian graphical modeling reconstructs pathway reactions from high-throughput metabolomics data. BMC Syst Biol 5, 21.
34.Benjamini, Y & Hochberg, Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Statist Soc B 57, 289–300.
35.Kushner, I, Rzewnicki, D & Samols, D (2006) What does minor elevation of C-reactive protein signify? Am J Med 119, 166.e117–166.e128.
36.Gylling, B, Myte, R, Schneede, J, et al. (2017) Vitamin B-6 and colorectal cancer risk: a prospective population-based study using 3 distinct plasma markers of vitamin B-6 status. Am J Clin Nutr 105, 897–904.
37.Larsson, SC, Orsini, N & Wolk, A (2010) Vitamin B6 and risk of colorectal cancer: a meta-analysis of prospective studies. JAMA 303, 1077–1083.
38.Je, Y, Lee, JE, Ma, J, et al. (2013) Prediagnostic plasma vitamin B6 (pyridoxal 5'-phosphate) and survival in patients with colorectal cancer. Cancer Causes Control 24, 719–729.
39.Hvas, AM, Juul, S, Bech, P, et al. (2004) Vitamin B6 level is associated with symptoms of depression. Psychother Psychosom 73, 340–343.
40.Saibeni, S, Cattaneo, M, Vecchi, M, et al. (2003) Low vitamin B(6) plasma levels, a risk factor for thrombosis, in inflammatory bowel disease: role of inflammation and correlation with acute phase reactants. Am J Gastroenterol 98, 112–117.
41.Huang, SC, Wei, JC, Wu, DJ, et al. (2010) Vitamin B(6) supplementation improves pro-inflammatory responses in patients with rheumatoid arthritis. Eur J Clin Nutr 64, 1007–1013.
42.Morris, MS, Sakakeeny, L, Jacques, PF, et al. (2010) Vitamin B-6 intake is inversely related to, and the requirement is affected by, inflammation status. J Nutr 140, 103–110.
43.Paul, L, Ueland, PM & Selhub, J (2013) Mechanistic perspective on the relationship between pyridoxal 5'-phosphate and inflammation. Nutr Rev 71, 239–244.
44.Zhang, P, Tsuchiya, K, Kinoshita, T, et al. (2016) Vitamin B6 prevents IL-1beta protein production by inhibiting NLRP3 inflammasome activation. J Biol Chem 291, 24517–24527.
45.Abbas, T, Dutta, A (2009) p21 in cancer: intricate networks and multiple activities. Nat Rev Cancer 9, 400–414.
46.Zhang, P, Suidasari, S, Hasegawa, T, et al. (2014) Vitamin B(6) activates p53 and elevates p21 gene expression in cancer cells and the mouse colon. Oncol Rep 31, 2371–2376.
47.Bessler, H & Djaldetti, M (2016) Vitamin B6 modifies the immune cross-talk between mononuclear and colon carcinoma cells. Folia Biol 62, 47–52.
48.Park, J, Morley, TS, Kim, M, et al. (2014) Obesity and cancer – mechanisms underlying tumour progression and recurrence. Nat Rev Endocrinol 10, 455–465.
49.Shoelson, SE, Herrero, L & Naaz, A (2007) Obesity, inflammation, and insulin resistance. Gastroenterology 132, 2169–2180.
50.Nicklas, BJ, Ambrosius, W, Messier, SP, et al. (2004) Diet-induced weight loss, exercise, and chronic inflammation in older, obese adults: a randomized controlled clinical trial. Am J Clin Nutr 79, 544–551.
51.Zuo, H, Tell, GS, Ueland, PM, et al. (2018) The PAr index, an indicator reflecting altered vitamin B-6 homeostasis, is associated with long-term risk of stroke in the general population: the Hordaland Health Study (HUSK). Am J Clin Nutr 107, 105–112.
52.Zuo, H, Ueland, PM, Midttun, Ø, et al. (2018) Results from the European prospective investigation into cancer and nutrition link vitamin B6 catabolism and lung cancer risk. Cancer Res 78, 302.
53.Ulvik, A, Pedersen, ER, Svingen, GFT, et al. (2016) Vitamin B-6 catabolism and long-term mortality risk in patients with coronary artery disease. Am J Clin Nutr 103, 1417–1425.
54.Cianciolo, G, La Manna, G, Coli, L, et al. (2008) 5-methyltetrahydrofolate administration is associated with prolonged survival and reduced inflammation in ESRD patients. Am J Nephrol 28, 941–948.
55.Hannisdal, R, Svardal, A & Ueland, PM (2008) Measurement of folate in fresh and archival serum samples as p-amobenzoylglutamate equivalents. Clin Chem 54, 665–672.
56.Fatahi, S, Pezeshki, M, Mousavi, SM, et al. (2018) The effects of folic acid supplementation on C-reactive protein: a systematic review and meta-analysis of randomized controlled trials. Nutr Metab Cardiovasc Dis 29, 432–439.
57.Ho, GYF, Xue, X, Cushman, M, et al. (2009) Antagonistic effects of aspirin and folic acid on inflammation markers and subsequent risk of recurrent colorectal adenomas. J Natl Cancer Inst 101, 1650–1654.
58.Suh, JR, Herbig, AK & Stover, PJ (2001) New perspectives on folate catabolism. Annu Rev Nutr 21, 255–282.
59.Kim, Y-I (2008) Folic acid supplementation and cancer risk: point. Cancer Epidemiol Biomarkers Prev 17, 2220–2225.
60.Luebeck, EG, Moolgavkar, SH, Liu, AY, et al. (2008) Does folic acid supplementation prevent or promote colorectal cancer? Results from model-based predictions. Cancer Epidemiol Biomarkers Prev 17, 1360–1367.
61.Miller, JW & Ulrich, CM (2013) Folic acid and cancer – where are we today? Lancet 381, 974–976.
62.Ulrich, CM (2007) Folate and cancer prevention: a closer look at a complex picture. Am J Clin Nutr 86, 271–273.
63.Ulrich, CM & Potter, JD (2007) Folate and cancer – timing is everything. JAMA 297, 2408–2409.
64.Ebbing, M, Bonaa, KH, Nygard, O, et al. (2009) Cancer incidence and mortality after treatment with folic acid and vitamin B12. JAMA 302, 2119–2126.
65.Matsubara, K, Mori, M, Matsuura, Y, et al. (2001) Pyridoxal 5'-phosphate and pyridoxal inhibit angiogenesis in serum-free rat aortic ring assay. Int J Mol Med 8, 505–508.
66.Matsubara, K, Mori, M, Akagi, R, et al. (2004) Anti-angiogenic effect of pyridoxal 5'-phosphate, pyridoxal and pyridoxamine on embryoid bodies derived from mouse embryonic stem cells. Int J Mol Med 14, 819–823.
67.George, ML, Tutton, MG, Janssen, F, et al. (2001) VEGF-A, VEGF-C, and VEGF-D in colorectal cancer progression. Neoplasia 3, 420–427.
68.Zastre, JA, Sweet, RL, Hanberry, BS, et al. (2013) Linking vitamin B1 with cancer cell metabolism. Cancer Metab 1, 16.
69.Alaei-Shahmiri, F, Soares, MJ, Zhao, Y, et al. (2015) The impact of thiamine supplementation on blood pressure, serum lipids and C-reactive protein in individuals with hyperglycemia: a randomised, double-blind cross-over trial. Diabetes Metab Syndr 9, 213–217.
70.González-Ortiz, M, Martínez-Abundis, E, Robles-Cervantes, JA, et al. (2011) Effect of thiamine administration on metabolic profile, cytokines and inflammatory markers in drug-naïve patients with type 2 diabetes. Eur J Nutr 50, 145–149.
71.Page, GL, Laight, D & Cummings, MH (2011) Thiamine deficiency in diabetes mellitus and the impact of thiamine replacement on glucose metabolism and vascular disease. Int J Clin Pract 65, 684–690.
72.de Andrade, JAA, Gayer, CRM, Nogueira, NPdA, et al. (2014) The effect of thiamine deficiency on inflammation, oxidative stress and cellular migration in an experimental model of sepsis. J Inflamm 11, 11.
73.Menezes, RR, Godin, AM, Rodrigues, FF, et al. (2017) Thiamine and riboflavin inhibit production of cytokines and increase the anti-inflammatory activity of a corticosteroid in a chronic model of inflammation induced by complete Freund’s adjuvant. Pharmacol Rep 69, 1036–1043.
74.Yadav, UCS, Kalariya, NM, Srivastava, SK, et al. (2010) Protective role of benfotiamine, a fat-soluble vitamin B1 analogue, in lipopolysaccharide-induced cytotoxic signals in murine macrophages. Free Radical Biol Med 48, 1423–1434.
75.Ross, R (1999) Atherosclerosis – an inflammatory disease. N Engl J Med 340, 115–126.
76.Araki, A, Hosoi, T, Orimo, H, et al. (2005) Association of plasma homocysteine with serum interleukin-6 and C-peptide levels in patients with type 2 diabetes. Metabolism 54, 809–814.
77.Gori, AM, Corsi, AM, Fedi, S, et al. (2005) A proinflammatory state is associated with hyperhomocysteinemia in the elderly. Am J Clin Nutr 82, 335–341.
78.Scheller, J, Chalaris, A, Schmidt-Arras, D, et al. (2011) The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta 1813, 878–888.
79.Schett, G (2018) Physiological effects of modulating the interleukin-6 axis. Rheumatology 57, ii43–ii50.
80.Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate OBV, and Choline (1998) Vitamin B6. In Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academies Press.
81.Evans, C, Morrison, I, Heriot, AG, et al. (2006) The correlation between colorectal cancer rates of proliferation and apoptosis and systemic cytokine levels; plus their influence upon survival. Br J Cancer 94, 1412–1419.