Skip to main content
Top
Published in: BMC Cancer 1/2009

Open Access 01-12-2009 | Study protocol

A study protocol to investigate the relationship between dietary fibre intake and fermentation, colon cell turnover, global protein acetylation and early carcinogenesis: the FACT study

Authors: Bernard M Corfe, Elizabeth A Williams, Jonathan P Bury, Stuart A Riley, Lisa J Croucher, Daphne YL Lai, Caroline A Evans

Published in: BMC Cancer | Issue 1/2009

Login to get access

Abstract

Background

A number of studies, notably EPIC, have shown a descrease in colorectal cancer risk associated with increased fibre consumption. Whilst the underlying mechanisms are likely to be multifactorial, production of the short-chain fatty-acid butyrate fro butyratye is frequently cited as a major potential contributor to the effect. Butyrate inhibits histone deacetylases, which work on a wide range of proteins over and above histones. We therefore hypothesized that alterations in the acetylated proteome may be associated with a cancer risk phenotype in the colorectal mucosa, and that such alterations are candidate biomarkers for effectiveness of fibre interventions in cancer prevention.

Methods an design

There are two principal arms to this study: (i) a cross-sectional study (FACT OBS) of 90 subjects recruited from gastroenterology clinics and; (ii) an intervention trial in 40 subjects with an 8 week high fibre intervention. In both studies the principal goal is to investigate a link between fibre intake, SCFA production and global protein acetylation. The primary measure is level of faecal butyrate, which it is hoped will be elevated by moving subjects to a high fibre diet. Fibre intakes will be estimated in the cross-sectional group using the EPIC Food Frequency Questionnaire. Subsidiary measures of the effect of butyrate on colon mucosal function and pre-cancerous phenotype will include measures of apoptosis, apoptotic regulators cell cycle and cell division.

Discussion

This study will provide a new level of mechanistic data on alterations in the functional proteome in response to the colon microenvironment which may underwrite the observed cancer preventive effect of fibre. The study may yield novel candidate biomarkers of fibre fermentation and colon mucosal function.

Trial Registration

Trial Registration Number: ISRCTN90852168
Appendix
Available only for authorised users
Literature
1.
go back to reference Burkitt DP: Related disease - related cause?. Lancet. 1969, 2 (7632): 1229-1231. 10.1016/S0140-6736(69)90757-0.CrossRefPubMed Burkitt DP: Related disease - related cause?. Lancet. 1969, 2 (7632): 1229-1231. 10.1016/S0140-6736(69)90757-0.CrossRefPubMed
2.
go back to reference World Cancer Research Fund/American Institute for Cancer Research: Food, nutrition, physical activity and the prevention of cancer: a global perspective. 2007, Washington DC: AICR World Cancer Research Fund/American Institute for Cancer Research: Food, nutrition, physical activity and the prevention of cancer: a global perspective. 2007, Washington DC: AICR
3.
go back to reference Bonithon-Kopp C, Kronborg O, Giacosa A, Räth U, Faivre J: Calcium and fibre supplementation in prevention of colorectal adenoma recurrence: a randomised intervention trial. European Cancer Prevention Organisation Study Group. Lancet. 2000, 356: 1300-6. 10.1016/S0140-6736(00)02813-0.CrossRefPubMed Bonithon-Kopp C, Kronborg O, Giacosa A, Räth U, Faivre J: Calcium and fibre supplementation in prevention of colorectal adenoma recurrence: a randomised intervention trial. European Cancer Prevention Organisation Study Group. Lancet. 2000, 356: 1300-6. 10.1016/S0140-6736(00)02813-0.CrossRefPubMed
4.
go back to reference Schatzkin A, Lanza E, Corle D, Lance P, Iber F, Caan B, Shike M, Weissfeld J, Burt R, Cooper MR, Kikendall JW, Cahill J: Lack of effect of a low-fat, high-fiber diet on the recurrence of colorectal adenomas. Polyp Prevention Trial Study Group. N Engl J Med. 2000, 342: 1149-55. 10.1056/NEJM200004203421601.CrossRefPubMed Schatzkin A, Lanza E, Corle D, Lance P, Iber F, Caan B, Shike M, Weissfeld J, Burt R, Cooper MR, Kikendall JW, Cahill J: Lack of effect of a low-fat, high-fiber diet on the recurrence of colorectal adenomas. Polyp Prevention Trial Study Group. N Engl J Med. 2000, 342: 1149-55. 10.1056/NEJM200004203421601.CrossRefPubMed
5.
go back to reference Hill MJ: Vegetables, fruits, fibre and colorectal cancer. Eur J Cancer Prev. 2002, 11: 1-2. 10.1097/00008469-200202000-00001.CrossRefPubMed Hill MJ: Vegetables, fruits, fibre and colorectal cancer. Eur J Cancer Prev. 2002, 11: 1-2. 10.1097/00008469-200202000-00001.CrossRefPubMed
7.
go back to reference McIntyre A, Gibson PR, Young GP: Butyrate production from dietary fibre and protection against large bowel cancer in a rat model. Gut. 1993, 34: 386-91. 10.1136/gut.34.3.386.CrossRefPubMedPubMedCentral McIntyre A, Gibson PR, Young GP: Butyrate production from dietary fibre and protection against large bowel cancer in a rat model. Gut. 1993, 34: 386-91. 10.1136/gut.34.3.386.CrossRefPubMedPubMedCentral
8.
go back to reference Roediger WE: Utilization of nutrients by isolated epithelial cells of the rat colon. Gastroenterology. 1982, 83: 424-9.PubMed Roediger WE: Utilization of nutrients by isolated epithelial cells of the rat colon. Gastroenterology. 1982, 83: 424-9.PubMed
9.
go back to reference Toscani A, Soprano DR, Soprano KJ: Molecular analysis of sodium butyrate-induced growth arrest. Oncogene Res. 1988, 3: 223-38.PubMed Toscani A, Soprano DR, Soprano KJ: Molecular analysis of sodium butyrate-induced growth arrest. Oncogene Res. 1988, 3: 223-38.PubMed
10.
go back to reference Hofmanová J, Vaculová A, Koubková Z, Hýžd'alová M, Kozubík A: Human fetal colon cells and colon cancer cells respond differently to butyrate and PUFAs. Mol Nutr Food Res. 2009, 53: S102-113.CrossRefPubMed Hofmanová J, Vaculová A, Koubková Z, Hýžd'alová M, Kozubík A: Human fetal colon cells and colon cancer cells respond differently to butyrate and PUFAs. Mol Nutr Food Res. 2009, 53: S102-113.CrossRefPubMed
11.
go back to reference Prais AL, Dive C, Corfe BM: Butyrate-mediated cell cycle arrest of HCT116 colon carcinoma cells is accompanied by hyperploidy. Proceedings of Hydrocolloids as Gums and Stabilisers in the Food Industry 12. Edited by: Williams PA, Phillips GO. 2004, Royal Society of Chemistry, Cambridge Prais AL, Dive C, Corfe BM: Butyrate-mediated cell cycle arrest of HCT116 colon carcinoma cells is accompanied by hyperploidy. Proceedings of Hydrocolloids as Gums and Stabilisers in the Food Industry 12. Edited by: Williams PA, Phillips GO. 2004, Royal Society of Chemistry, Cambridge
12.
go back to reference Ruemmele FM, Dionne S, Qureshi I, Sarma DS, Levy E, Seidman EG: Butyrate mediates Caco-2 cell apoptosis via up-regulation of pro-apoptotic BAK and inducing caspase-3 mediated cleavage of poly-(ADP-ribose) polymerase (PARP). Cell Death Differ. 1999, 6: 729-35. 10.1038/sj.cdd.4400545.CrossRefPubMed Ruemmele FM, Dionne S, Qureshi I, Sarma DS, Levy E, Seidman EG: Butyrate mediates Caco-2 cell apoptosis via up-regulation of pro-apoptotic BAK and inducing caspase-3 mediated cleavage of poly-(ADP-ribose) polymerase (PARP). Cell Death Differ. 1999, 6: 729-35. 10.1038/sj.cdd.4400545.CrossRefPubMed
13.
go back to reference Ruemmele FM, Schwartz S, Seidman EG, Dionne S, Levy E, Lentze MJ: Butyrate induced Caco-2 cell apoptosis is mediated via the mitochondrial pathway. Gut. 2003, 52: 94-100. 10.1136/gut.52.1.94.CrossRefPubMedPubMedCentral Ruemmele FM, Schwartz S, Seidman EG, Dionne S, Levy E, Lentze MJ: Butyrate induced Caco-2 cell apoptosis is mediated via the mitochondrial pathway. Gut. 2003, 52: 94-100. 10.1136/gut.52.1.94.CrossRefPubMedPubMedCentral
14.
go back to reference Chirakkal H, Leech SH, Brookes KE, Prais AL, Waby JS, Corfe BM: Upregulation of BAK by butyrate in the colon is associated with increased Sp3 binding. Oncogene. 2006, 25: 7192-200. 10.1038/sj.onc.1209702.CrossRefPubMed Chirakkal H, Leech SH, Brookes KE, Prais AL, Waby JS, Corfe BM: Upregulation of BAK by butyrate in the colon is associated with increased Sp3 binding. Oncogene. 2006, 25: 7192-200. 10.1038/sj.onc.1209702.CrossRefPubMed
15.
go back to reference Inagaki A, Sakata T: Dose-dependent stimulatory and inhibitory effects of luminal and serosal n-butyric acid on epithelial cell proliferation of pig distal colonic mucosa. J Nutr Sci Vitaminol (Tokyo). 2005, 51: 156-60.CrossRef Inagaki A, Sakata T: Dose-dependent stimulatory and inhibitory effects of luminal and serosal n-butyric acid on epithelial cell proliferation of pig distal colonic mucosa. J Nutr Sci Vitaminol (Tokyo). 2005, 51: 156-60.CrossRef
16.
go back to reference Sakata T, von Engelhardt W: Stimulatory effect of short chain fatty acids on the epithelial cell proliferation in rat large intestine. Comp Biochem Physiol A Comp Physiol. 1983, 74: 459-62. 10.1016/0300-9629(83)90631-X.CrossRefPubMed Sakata T, von Engelhardt W: Stimulatory effect of short chain fatty acids on the epithelial cell proliferation in rat large intestine. Comp Biochem Physiol A Comp Physiol. 1983, 74: 459-62. 10.1016/0300-9629(83)90631-X.CrossRefPubMed
17.
go back to reference Sakata T, Kojima T, Fujeida M, Takahashi M, Michibata T: Influences of probiotic bacteria on organic acids production by pig caecal bacteria in vitro. Proc Nutr Soc. 2003, 62: 73-80. 10.1079/PNS2002211.CrossRefPubMed Sakata T, Kojima T, Fujeida M, Takahashi M, Michibata T: Influences of probiotic bacteria on organic acids production by pig caecal bacteria in vitro. Proc Nutr Soc. 2003, 62: 73-80. 10.1079/PNS2002211.CrossRefPubMed
18.
go back to reference Hass R, Busche R, Luciano L, Reale E, Engelhardt WV: Lack of butyrate is associated with induction of Bax and subsequent apoptosis in the proximal colon of guinea pig. Gastroenterology. 1997, 112: 875-81. 10.1053/gast.1997.v112.pm9041249.CrossRefPubMed Hass R, Busche R, Luciano L, Reale E, Engelhardt WV: Lack of butyrate is associated with induction of Bax and subsequent apoptosis in the proximal colon of guinea pig. Gastroenterology. 1997, 112: 875-81. 10.1053/gast.1997.v112.pm9041249.CrossRefPubMed
19.
go back to reference Cole JW, Holden WD: Postcolectomy regression of adenomatous polyps of the rectum. Arch Surg. 1959, 79: 385-92.CrossRefPubMed Cole JW, Holden WD: Postcolectomy regression of adenomatous polyps of the rectum. Arch Surg. 1959, 79: 385-92.CrossRefPubMed
20.
go back to reference Scheppach W, Sommer H, Kirchner T, Paganelli GM, Bartram P, Christl S, Richter F, Dusel G, Kasper H: Effect of butyrate enemas on the colonic mucosa in distal ulcerative colitis. Gastroenterology. 1992, 103: 51-6.CrossRefPubMed Scheppach W, Sommer H, Kirchner T, Paganelli GM, Bartram P, Christl S, Richter F, Dusel G, Kasper H: Effect of butyrate enemas on the colonic mucosa in distal ulcerative colitis. Gastroenterology. 1992, 103: 51-6.CrossRefPubMed
21.
go back to reference Le Leu RK, Hu Y, Young GP: Effects of resistant starch and nonstarch polysaccharides on colonic luminal environment and genotoxin-induced apoptosis in the rat. Carcinogenesis. 2002, 23: 713-9. 10.1093/carcin/23.5.713.CrossRefPubMed Le Leu RK, Hu Y, Young GP: Effects of resistant starch and nonstarch polysaccharides on colonic luminal environment and genotoxin-induced apoptosis in the rat. Carcinogenesis. 2002, 23: 713-9. 10.1093/carcin/23.5.713.CrossRefPubMed
22.
go back to reference Le Leu RK, Brown IL, Hu Y, Young GP: Effect of resistant starch on genotoxin-induced apoptosis, colonic epithelium, and lumenal contents in rats. Carcinogenesis. 2003, 24: 1347-52. 10.1093/carcin/bgg098.CrossRefPubMed Le Leu RK, Brown IL, Hu Y, Young GP: Effect of resistant starch on genotoxin-induced apoptosis, colonic epithelium, and lumenal contents in rats. Carcinogenesis. 2003, 24: 1347-52. 10.1093/carcin/bgg098.CrossRefPubMed
23.
go back to reference Sealy L, Chalkley R: The effect of sodium butyrate on histone modification. Cell. 1978, 14: 115-21. 10.1016/0092-8674(78)90306-9.CrossRefPubMed Sealy L, Chalkley R: The effect of sodium butyrate on histone modification. Cell. 1978, 14: 115-21. 10.1016/0092-8674(78)90306-9.CrossRefPubMed
24.
go back to reference Seigneurin-Berny D, Verdel A, Curtet S, Lemercier C, Garin J, Rousseaux S, Khochbin S: Identification of components of the murine histone deacetylase 6 complex: link between acetylation and ubiquitination signaling pathways. Mol Cell Biol. 2001, 21: 8035-44. 10.1128/MCB.21.23.8035-8044.2001.CrossRefPubMedPubMedCentral Seigneurin-Berny D, Verdel A, Curtet S, Lemercier C, Garin J, Rousseaux S, Khochbin S: Identification of components of the murine histone deacetylase 6 complex: link between acetylation and ubiquitination signaling pathways. Mol Cell Biol. 2001, 21: 8035-44. 10.1128/MCB.21.23.8035-8044.2001.CrossRefPubMedPubMedCentral
25.
go back to reference Sun JM, Spencer VA, Chen HY, Li L, Davie JR: Measurement of histone acetyltransferase and histone deacetylase activities and kinetics of histone acetylation. Methods. 2003, 31: 12-23. 10.1016/S1046-2023(03)00083-5.CrossRefPubMed Sun JM, Spencer VA, Chen HY, Li L, Davie JR: Measurement of histone acetyltransferase and histone deacetylase activities and kinetics of histone acetylation. Methods. 2003, 31: 12-23. 10.1016/S1046-2023(03)00083-5.CrossRefPubMed
26.
go back to reference Dwarakanath BS, Verma A, Bhatt AN, Parmar VS, Raj HG: Targeting protein acetylation for improving cancer therapy. Indian J Med Res. 2008, 128: 13-21.PubMed Dwarakanath BS, Verma A, Bhatt AN, Parmar VS, Raj HG: Targeting protein acetylation for improving cancer therapy. Indian J Med Res. 2008, 128: 13-21.PubMed
27.
go back to reference North BJ, Marshall BL, Borra MT, Denu JM, Verdin E: The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase. Mol Cell. 2003, 11: 437-44. 10.1016/S1097-2765(03)00038-8.CrossRefPubMed North BJ, Marshall BL, Borra MT, Denu JM, Verdin E: The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase. Mol Cell. 2003, 11: 437-44. 10.1016/S1097-2765(03)00038-8.CrossRefPubMed
28.
go back to reference Leech SH, Evans CA, Shaw L, Wong CH, Connolly J, Griffiths JR, Whetton AD, Corfe BM: Proteomic analyses of intermediate filaments reveals cytokeratin8 is highly acetylated--implications for colorectal epithelial homeostasis. Proteomics. 2008, 8: 279-88. 10.1002/pmic.200700404.CrossRefPubMed Leech SH, Evans CA, Shaw L, Wong CH, Connolly J, Griffiths JR, Whetton AD, Corfe BM: Proteomic analyses of intermediate filaments reveals cytokeratin8 is highly acetylated--implications for colorectal epithelial homeostasis. Proteomics. 2008, 8: 279-88. 10.1002/pmic.200700404.CrossRefPubMed
29.
go back to reference Seal CJ, Mathers JC: Comparative gastrointestinal and plasma cholesterol responses of rats fed on cholesterol-free diets supplemented with guar gum and sodium alginate. Br J Nutr. 2001, 85: 317-24. 10.1079/BJN2000250.CrossRefPubMed Seal CJ, Mathers JC: Comparative gastrointestinal and plasma cholesterol responses of rats fed on cholesterol-free diets supplemented with guar gum and sodium alginate. Br J Nutr. 2001, 85: 317-24. 10.1079/BJN2000250.CrossRefPubMed
30.
go back to reference Kim SC, Sprung R, Chen Y, Xu Y, Ball H, Pei J, Cheng T, Kho Y, Xiao H, Xiao L, Grishin NV, White M, Yang XJ, Zhao Y: Substrate and Functional Diversity of Lysine Acetylation Revealed by a Proteomics Survey. Mol Cell. 2006, 23: 607-618. 10.1016/j.molcel.2006.06.026.CrossRefPubMed Kim SC, Sprung R, Chen Y, Xu Y, Ball H, Pei J, Cheng T, Kho Y, Xiao H, Xiao L, Grishin NV, White M, Yang XJ, Zhao Y: Substrate and Functional Diversity of Lysine Acetylation Revealed by a Proteomics Survey. Mol Cell. 2006, 23: 607-618. 10.1016/j.molcel.2006.06.026.CrossRefPubMed
31.
go back to reference Karp NA, Feret R, Rubtsov DV, Lilley KS: Comparison of DIGE and post-stained gel electrophoresis with both traditional and SameSpots analysis for quantitative proteomics. Proteomics. 2008, 8: 948-60. 10.1002/pmic.200700812.CrossRefPubMed Karp NA, Feret R, Rubtsov DV, Lilley KS: Comparison of DIGE and post-stained gel electrophoresis with both traditional and SameSpots analysis for quantitative proteomics. Proteomics. 2008, 8: 948-60. 10.1002/pmic.200700812.CrossRefPubMed
32.
go back to reference Glen A, Gan CS, Hamdy FC, Eaton CL, Cross SS, Catto JW, Wright PC, Rehman I: iTRAQ-facilitated proteomic analysis of human prostate cancer cells identifies proteins associated with progression. J Proteome Res. 2008, 7: 897-907. 10.1021/pr070378x.CrossRefPubMed Glen A, Gan CS, Hamdy FC, Eaton CL, Cross SS, Catto JW, Wright PC, Rehman I: iTRAQ-facilitated proteomic analysis of human prostate cancer cells identifies proteins associated with progression. J Proteome Res. 2008, 7: 897-907. 10.1021/pr070378x.CrossRefPubMed
33.
go back to reference Alferez D, Goodlad RA: To best measure cell proliferation in samples from the intestine. Cell Prolif. 2007, 40: 231-40. 10.1111/j.1365-2184.2007.00427.x.CrossRefPubMed Alferez D, Goodlad RA: To best measure cell proliferation in samples from the intestine. Cell Prolif. 2007, 40: 231-40. 10.1111/j.1365-2184.2007.00427.x.CrossRefPubMed
34.
go back to reference Goodlad RA, Levi S, Lee CY, Mandir N, Hodgson H, Wright NA: Morphometry and cell proliferation in endoscopic biopsies: evaluation of a technique. Gastroenterology. 1991, 101: 1235-41.CrossRefPubMed Goodlad RA, Levi S, Lee CY, Mandir N, Hodgson H, Wright NA: Morphometry and cell proliferation in endoscopic biopsies: evaluation of a technique. Gastroenterology. 1991, 101: 1235-41.CrossRefPubMed
35.
go back to reference Croucher L, Norwood H, Riley S, Williams E, Corfe B, Bury J: Assessing proliferation in colorectal biopsies: a comparison of Ki-67 immunohistochemistry with counting mitoses in whole crypts. J Pathol. 2007, 213: 9A- Croucher L, Norwood H, Riley S, Williams E, Corfe B, Bury J: Assessing proliferation in colorectal biopsies: a comparison of Ki-67 immunohistochemistry with counting mitoses in whole crypts. J Pathol. 2007, 213: 9A-
36.
go back to reference Hanahan D, Weinberg RA: The hallmarks of cancer. Cell. 2000, 100: 57-70. 10.1016/S0092-8674(00)81683-9.CrossRefPubMed Hanahan D, Weinberg RA: The hallmarks of cancer. Cell. 2000, 100: 57-70. 10.1016/S0092-8674(00)81683-9.CrossRefPubMed
Metadata
Title
A study protocol to investigate the relationship between dietary fibre intake and fermentation, colon cell turnover, global protein acetylation and early carcinogenesis: the FACT study
Authors
Bernard M Corfe
Elizabeth A Williams
Jonathan P Bury
Stuart A Riley
Lisa J Croucher
Daphne YL Lai
Caroline A Evans
Publication date
01-12-2009
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2009
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-9-332

Other articles of this Issue 1/2009

BMC Cancer 1/2009 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine