Imperial College London

Professor Sir Huw Thomas

Faculty of MedicineDepartment of Surgery & Cancer

Professor
 
 
 
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Contact

 

+44 (0)20 8235 4266huw.thomas

 
 
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Location

 

St Marks HospitalNorthwick Park and St Marks Site

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Summary

 

Publications

Publication Type
Year
to

134 results found

Monahan KJ, Lincoln A, East JE, Benton S, Burn J, DeSouza B, Hanson H, Lalloo F, McVeigh T, Rutter MD, Snape K, Thomas HJW, Sasieni Pet al., 2020, Management strategies for the colonoscopic surveillance of people with Lynch syndrome during the COVID-19 pandemic, Gut, ISSN: 0017-5749

Journal article

Burn J, Sheth H, Elliott F, Reed L, Macrae F, Mecklin J-P, Möslein G, McRonald FE, Bertario L, Evans DG, Gerdes A-M, Ho JWC, Lindblom A, Morrison PJ, Rashbass J, Ramesar R, Seppälä T, Thomas HJW, Pylvänäinen K, Borthwick GM, Mathers JC, Bishop DT, CAPP2 Investigatorset al., 2020, Cancer prevention with aspirin in hereditary colorectal cancer (Lynch syndrome), 10-year follow-up and registry-based 20-year data in the CAPP2 study: a double-blind, randomised, placebo-controlled trial, The Lancet, Vol: 395, Pages: 1855-1863, ISSN: 0140-6736

BACKGROUND: Lynch syndrome is associated with an increased risk of colorectal cancer and with a broader spectrum of cancers, especially endometrial cancer. In 2011, our group reported long-term cancer outcomes (mean follow-up 55·7 months [SD 31·4]) for participants with Lynch syndrome enrolled into a randomised trial of daily aspirin versus placebo. This report completes the planned 10-year follow-up to allow a longer-term assessment of the effect of taking regular aspirin in this high-risk population. METHODS: In the double-blind, randomised CAPP2 trial, 861 patients from 43 international centres worldwide (707 [82%] from Europe, 112 [13%] from Australasia, 38 [4%] from Africa, and four [<1%] from The Americas) with Lynch syndrome were randomly assigned to receive 600 mg aspirin daily or placebo. Cancer outcomes were monitored for at least 10 years from recruitment with English, Finnish, and Welsh participants being monitored for up to 20 years. The primary endpoint was development of colorectal cancer. Analysis was by intention to treat and per protocol. The trial is registered with the ISRCTN registry, number ISRCTN59521990. FINDINGS: Between January, 1999, and March, 2005, 937 eligible patients with Lynch syndrome, mean age 45 years, commenced treatment, of whom 861 agreed to be randomly assigned to the aspirin group or placebo; 427 (50%) participants received aspirin and 434 (50%) placebo. Participants were followed for a mean of 10 years approximating 8500 person-years. 40 (9%) of 427 participants who received aspirin developed colorectal cancer compared with 58 (13%) of 434 who received placebo. Intention-to-treat Cox proportional hazards analysis revealed a significantly reduced hazard ratio (HR) of 0·65 (95% CI 0·43-0·97; p=0·035) for aspirin versus placebo. Negative binomial regression to account for multiple primary events gave an incidence rate ratio of 0·58 (0·39-0·87; p=0·0085). P

Journal article

Monahan KJ, Bradshaw N, Dolwani S, Desouza B, Dunlop MG, East JE, Ilyas M, Kaur A, Lalloo F, Latchford A, Rutter MD, Tomlinson I, Thomas HJW, Hill J, Hereditary CRC guidelines eDelphi consensus groupet al., 2020, Guidelines for the management of hereditary colorectal cancer from the British Society of Gastroenterology (BSG)/Association of Coloproctology of Great Britain and Ireland (ACPGBI)/United Kingdom Cancer Genetics Group (UKCGG), Gut, Vol: 69, Pages: 411-444, ISSN: 0017-5749

Heritable factors account for approximately 35% of colorectal cancer (CRC) risk, and almost 30% of the population in the UK have a family history of CRC. The quantification of an individual's lifetime risk of gastrointestinal cancer may incorporate clinical and molecular data, and depends on accurate phenotypic assessment and genetic diagnosis. In turn this may facilitate targeted risk-reducing interventions, including endoscopic surveillance, preventative surgery and chemoprophylaxis, which provide opportunities for cancer prevention. This guideline is an update from the 2010 British Society of Gastroenterology/Association of Coloproctology of Great Britain and Ireland (BSG/ACPGBI) guidelines for colorectal screening and surveillance in moderate and high-risk groups; however, this guideline is concerned specifically with people who have increased lifetime risk of CRC due to hereditary factors, including those with Lynch syndrome, polyposis or a family history of CRC. On this occasion we invited the UK Cancer Genetics Group (UKCGG), a subgroup within the British Society of Genetic Medicine (BSGM), as a partner to BSG and ACPGBI in the multidisciplinary guideline development process. We also invited external review through the Delphi process by members of the public as well as the steering committees of the European Hereditary Tumour Group (EHTG) and the European Society of Gastrointestinal Endoscopy (ESGE). A systematic review of 10 189 publications was undertaken to develop 67 evidence and expert opinion-based recommendations for the management of hereditary CRC risk. Ten research recommendations are also prioritised to inform clinical management of people at hereditary CRC risk.

Journal article

Burn J, Alsina D, Hill J, Rees C, Tischkowitz M, Monahan K, Thomas H, Rutter M, Fearnhead N, Evans G, Lalloo F, Atkin Wet al., 2017, Response: A clinical consensus on improving the colonoscopic screening and surveillance of people with Lynch syndrome in England, British Medical Journal, Vol: 356, ISSN: 0959-8138

Journal article

Monahan KJ, Alsina D, Bach S, Buchanan J, Burn J, Clark S, Dawson P, De Souza B, Din FVN, Dolwani S, Dunlop MG, East J, Evans DG, Fearnhead N, Frayling IM, Glynne-Jones R, Hill J, Houlston R, Hull M, Lalloo F, Latchford A, Lishman S, Quirke P, Rees C, Rutter M, Sasieni P, Senapati A, Speake D, Thomas H, Tomlinson Iet al., 2017, Urgent improvements needed to diagnose and manage Lynch syndrome, BMJ-BRITISH MEDICAL JOURNAL, Vol: 356, ISSN: 1756-1833

Journal article

Movahedi M, Bishop DT, Macrae F, Mecklin J-P, Moeslein G, Olschwang S, Eccles D, Evans DG, Maher ER, Bertario L, Bisgaard M-L, Dunlop MG, Ho JWC, Hodgson SV, Lindblom A, Lubinski J, Morrison PJ, Murday V, Ramesar RS, Side L, Scott RJ, Thomas HJW, Vasen HF, Burn J, Mathers JCet al., 2015, Obesity, aspirin, and risk of colorectal cancer in carriers of hereditary colorectal cancer: a prospective investigation in the CAPP2 study, Journal of Clinical Oncology, Vol: 33, Pages: 3591-3597, ISSN: 0732-183X

PurposeIn the general population, increased adiposity is a significant risk factor for colorectal cancer (CRC), but whether obesity has similar effects in those with hereditary CRC is uncertain. This prospective study investigated the association between body mass index and cancer risk in patients with Lynch syndrome (LS).Patients and MethodsParticipants with LS were recruited to the CAPP2 study, in which they were randomly assigned to receive aspirin 600 mg per day or aspirin placebo, plus resistant starch 30 g per day or starch placebo (2 × 2 factorial design). Mean intervention period was 25.0 months, and mean follow-up was 55.7 months.ResultsDuring follow-up, 55 of 937 participants developed CRC. For obese participants, CRC risk was 2.41× (95% CI, 1.22 to 4.85) greater than for underweight and normal-weight participants (reference group), and CRC risk increased by 7% for each 1-kg/m2 increase in body mass index. The risk of all LS-related cancers in obese people was 1.77× (95% CI, 1.06 to 2.96; P = .03) greater than for the reference group. In subgroup analysis, obesity was associated with 3.72× (95% CI, 1.41 to 9.81) greater CRC risk in patients with LS with MLH1 mutation, but no excess risk was observed in those with MSH2 or MSH6 mutation (P = .5). The obesity-related excess CRC risk was confined to those randomly assigned to the aspirin placebo group (adjusted hazard ratio, 2.75; 95% CI, 1.12 to 6.79; P = .03).ConclusionObesity is associated with substantially increased CRC risk in patients with LS, but this risk is abrogated in those taking aspirin. Such patients are likely to benefit from obesity prevention and/or regular aspirin.

Journal article

Cheng THT, Gorman M, Martin L, Barclay E, Casey G, Saunders B, Thomas H, Clark S, Tomlinson Iet al., 2015, Common colorectal cancer risk alleles contribute to the multiple colorectal adenoma phenotype, but do not influence colonic polyposis in FAP, EUROPEAN JOURNAL OF HUMAN GENETICS, Vol: 23, Pages: 260-263, ISSN: 1018-4813

Journal article

Davis H, Irshad S, Bansal M, Rafferty H, Boitsova T, Bardella C, Jaeger E, Lewis A, Freeman-Mills L, Giner FC, Rodenas-Cuadrado P, Mallappa S, Clark S, Thomas H, Jeffery R, Poulsom R, Rodriguez-Justo M, Novelli M, Chetty R, Silver A, Sansom OJ, Greten FR, Wang LM, East JE, Tomlinson I, Leedham SJet al., 2015, Aberrant epithelial GREM1 expression initiates colonic tumorigenesis from cells outside the stem cell niche, Nature Medicine, Vol: 21, Pages: 62-70, ISSN: 1546-170X

Hereditary mixed polyposis syndrome (HMPS) is characterized by the development of mixed-morphology colorectal tumors and is caused by a 40-kb genetic duplication that results in aberrant epithelial expression of the gene encoding mesenchymal bone morphogenetic protein antagonist, GREM1. Here we use HMPS tissue and a mouse model of the disease to show that epithelial GREM1 disrupts homeostatic intestinal morphogen gradients, altering cell fate that is normally determined by position along the vertical epithelial axis. This promotes the persistence and/or reacquisition of stem cell properties in Lgr5-negative progenitor cells that have exited the stem cell niche. These cells form ectopic crypts, proliferate, accumulate somatic mutations and can initiate intestinal neoplasia, indicating that the crypt base stem cell is not the sole cell of origin of colorectal cancer. Furthermore, we show that epithelial expression of GREM1 also occurs in traditional serrated adenomas, sporadic premalignant lesions with a hitherto unknown pathogenesis, and these lesions can be considered the sporadic equivalents of HMPS polyps.

Journal article

Mesher D, Dove-Edwin I, Sasieni P, Vasen H, Bernstein I, Royer-Pokora B, Holinski-Feder E, Lalloo F, Evans DG, Forsberg A, Lindblom A, Thomas Het al., 2014, A pooled analysis of the outcome of prospective colonoscopic surveillance for familial colorectal cancer, INTERNATIONAL JOURNAL OF CANCER, Vol: 134, Pages: 939-947, ISSN: 0020-7136

Journal article

Saunders BP, Tsiamoulos ZP, Thomas H, Warusavitarne Jet al., 2013, Rectal Endoscopic Submucosal Dissection Made Easy: A Solution to the Retraction Problem, GASTROENTEROLOGY, Vol: 145, Pages: 939-941, ISSN: 0016-5085

Journal article

Vasen HFA, Blanco I, Aktan-Collan K, Gopie JP, Alonso A, Aretz S, Bernstein I, Bertario L, Burn J, Capella G, Colas C, Engel C, Frayling IM, Genuardi M, Heinimann K, Hes FJ, Hodgson SV, Karagiannis JA, Lalloo F, Lindblom A, Mecklin J-P, Moller P, Myrhoj T, Nagengast FM, Parc Y, de Leon MP, Renkonen-Sinisalo L, Sampson JR, Stormorken A, Sijmons RH, Tejpar S, Thomas HJW, Rahner N, Wijnen JT, Jaervinen HJ, Moeslein Get al., 2013, Revised guidelines for the clinical management of Lynch syndrome (HNPCC): recommendations by a group of European experts, GUT, Vol: 62, Pages: 812-823, ISSN: 0017-5749

Journal article

Palles C, Cazier J-B, Howarth KM, Domingo E, Jones AM, Broderick P, Kemp Z, Spain SL, Almeida EG, Salguero I, Sherborne A, Chubb D, Carvajal-Carmona LG, Ma Y, Kaur K, Dobbins S, Barclay E, Gorman M, Martin L, Kovac MB, Humphray S, Lucassen A, Holmes CC, Bentley D, Donnelly P, Taylor J, Petridis C, Roylance R, Sawyer EJ, Kerr DJ, Clark S, Grimes J, Kearsey SE, Thomas HJW, McVean G, Houlston RS, Tomlinson Iet al., 2013, Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas, NATURE GENETICS, Vol: 45, Pages: 136-144, ISSN: 1061-4036

Journal article

Tomlinson I, Jaeger E, Leedham S, Thomas Het al., 2013, The classification of intestinal polyposis Reply, NATURE GENETICS, Vol: 45, Pages: 2-3, ISSN: 1061-4036

Journal article

Mathers JC, Movahedi M, Macrae F, Mecklin J-P, Moeslein G, Olschwang S, Eccles D, Evans G, Maher ER, Bertario L, Bisgaard M-L, Dunlop M, Ho JWC, Hodgson S, Lindblom A, Lubinski J, Morrison PJ, Murday V, Ramesar R, Side L, Scott RJ, Thomas HJW, Vasen H, Gerdes A-M, Barker G, Crawford G, Elliott F, Pylvanainen K, Wijnen J, Fodde R, Lynch H, Bishop DT, Burn Jet al., 2012, Long-term effect of resistant starch on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial, LANCET ONCOLOGY, Vol: 13, Pages: 1242-1249, ISSN: 1470-2045

Journal article

Nayagam S, Selvapatt N, Auguste JL, Williams HRT, Orchard TR, Thomas HJW, Teare JP, Hoare Jet al., 2012, QUALITY OF COLONOSCOPIC PROCEDURES AMONG INDEPENDENTLY PRACTISING GASTROENTEROLOGY TRAINEES IN A NW LONDON COHORT: ARE THEY REACHING NATIONAL STANDARDS?, GUT, Vol: 61, Pages: A59-A60, ISSN: 0017-5749

Journal article

Jaeger E, Leedham S, Lewis A, Segditsas S, Becker M, Cuadrado PR, Davis H, Kaur K, Heinimann K, Howarth K, East J, Taylor J, Thomas H, Tomlinson Iet al., 2012, Hereditary mixed polyposis syndrome is caused by a 40-kb upstream duplication that leads to increased and ectopic expression of the BMP antagonist GREM1, NATURE GENETICS, Vol: 44, Pages: 699-U127, ISSN: 1061-4036

Journal article

Burn J, Gerdes A-M, Macrae F, Mecklin J-P, Moeslein G, Olschwang S, Eccles D, Evans DG, Maher ER, Bertario L, Bisgaard M-L, Dunlop MG, Ho JWC, Hodgson SV, Lindblom A, Lubinski J, Morrison PJ, Murday V, Ramesar R, Side L, Scott RJ, Thomas HJW, Vasen HF, Barker G, Crawford G, Elliott F, Movahedi M, Pylvanainen K, Wijnen JT, Fodde R, Lynch HT, Mathers JC, Bishop DTet 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, Vol: 378, Pages: 2081-2087, ISSN: 0140-6736

Journal article

Walker DG, Williams HRT, Kane SP, Mawdsley JE, Arnold J, McNeil I, Thomas HJW, Teare JP, Hart AL, Pitcher MCL, Walters JRF, Marshall SE, Orchard TRet al., 2011, Differences in Inflammatory Bowel Disease Phenotype between South Asians and Northern Europeans Living in North West London, UK, AMERICAN JOURNAL OF GASTROENTEROLOGY, Vol: 106, Pages: 1281-1289, ISSN: 0002-9270

Journal article

Houlston RS, Cheadle J, Dobbins SE, Tenesa A, Jones AM, Howarth K, Spain SL, Broderick P, Domingo E, Farrington S, Prendergast JGD, Pittman AM, Theodoratou E, Smith CG, Olver B, Walther A, Barnetson RA, Churchman M, Jaeger EEM, Penegar S, Barclay E, Martin L, Gorman M, Mager R, Johnstone E, Midgley R, Niittymaki I, Tuupanen S, Colley J, Idziaszczyk S, Thomas HJW, Lucassen AM, Evans DGR, Maher ER, Maughan T, Dimas A, Dermitzakis E, Cazier J-B, Aaltonen LA, Pharoah P, Kerr DJ, Carvajal-Carmona LG, Campbell H, Dunlop MG, Tomlinson IPMet al., 2010, Meta-analysis of three genome-wide association studies identifies susceptibility loci for colorectal cancer at 1q41, 3q26.2, 12q13.13 and 20q13.33, NATURE GENETICS, Vol: 42, Pages: 973-U89, ISSN: 1061-4036

Journal article

Beggs AD, Latchford AR, Vasen HFA, Moslein G, Alonso A, Aretz S, Bertario L, Blanco I, Bulow S, Burn J, Capella G, Colas C, Friedl W, Moller P, Hes FJ, Jarvinen H, Mecklin J-P, Nagengast FM, Parc Y, Phillips RKS, Hyer W, de Leon MP, Renkonen-Sinisalo L, Sampson JR, Stormorken A, Tejpar S, Thomas HJW, Wijnen JT, Clark SK, Hodgson SVet al., 2010, Peutz-Jeghers syndrome: a systematic review and recommendations for management, GUT, Vol: 59, Pages: 975-986, ISSN: 0017-5749

Journal article

Vasen HFA, Moeslein G, Alonso A, Aretz S, Bernstein I, Bertario L, Blanco I, Bulow S, Burn J, Capella G, Colas C, Engel C, Frayling I, Rahner N, Hes FJ, Hodgson S, Mecklin J-P, Moller P, Myrhoj T, Nagengast FM, Parc Y, de Leon MP, Renkonen-Sinisalo L, Sampson JR, Stormorken A, Tejpar S, Thomas HJW, Wijnen J, Lubinski J, Jarvinen H, Claes E, Heinimann K, Karagiannis JA, Lindblom A, Dove-Edwin I, Mueller Het al., 2010, Recommendations to improve identification of hereditary and familial colorectal cancer in Europe, FAMILIAL CANCER, Vol: 9, Pages: 109-115, ISSN: 1389-9600

Journal article

Cairns SR, Scholefield JH, Steele RJ, Dunlop MG, Thomas HJW, Evans GD, Eaden JA, Rutter MD, Atkin WP, Saunders BP, Lucassen A, Jenkins P, Fairclough PD, Woodhouse CRJet al., 2010, Guidelines for colorectal cancer screening and surveillance in moderate and high risk groups (update from 2002), GUT, Vol: 59, Pages: 666-689, ISSN: 0017-5749

Journal article

Williams HRT, Cox IJ, Walker DG, North BV, Patel VM, Marshall SE, Jewell DP, Ghosh S, Thomas HJ, Teare JP, Jakobovits S, Zeki S, Welsh KI, Taylor-Robinson SD, Orchard TRet al., 2009, Erratum: Characterization of inflammatory bowel disease with urinary metabolic profiling (American Journal of Gastroenterology (2009) 104 (1435-1444) DOI: 10.1038 / ajg.2009.175), American Journal of Gastroenterology, Vol: 104, ISSN: 0002-9270

Journal article

Williams HRT, Cox IJ, Walker DG, North BV, Patel VM, Marshall SE, Jewell DP, Ghosh S, Thomas HJW, Teare JP, Jakobovits S, Zeki S, Welsh KI, Taylor-Robinson SD, Orchard TRet al., 2009, Characterization of Inflammatory Bowel Disease With Urinary Metabolic Profiling (vol 104, pg 1435, 2009), AMERICAN JOURNAL OF GASTROENTEROLOGY, Vol: 104, Pages: 1894-1894, ISSN: 0002-9270

Journal article

Williams HRT, Cox IJ, Walker DG, North BV, Patel VM, Marshall SE, Jewell DP, Ghosh S, Thomas HJW, Teare JP, Jakobovits S, Zeki S, Welsh KI, Taylor-Robinson SD, Orchard TRet al., 2009, Characterization of Inflammatory Bowel Disease With Urinary Metabolic Profiling, AMERICAN JOURNAL OF GASTROENTEROLOGY, Vol: 104, Pages: 1435-1444, ISSN: 0002-9270

Journal article

Monahan KJ, Spain S, Thomas HJW, Tomlinson IPet al., 2009, AN ASSOCIATION STUDY OF A MITOCHONDRIAL TUMOUR SUPPRESSOR 1 COPY NUMBER POLYMORPHISM AND COLORECTAL CANCER, Annual Meeting of the British-Society-of-Gastroenterology, Publisher: B M J PUBLISHING GROUP, Pages: A88-A88, ISSN: 0017-5749

Conference paper

Walker DG, Williams HRT, Padaruth S, Milestone AN, Arnold J, Kane S, Thomas HJW, Teare JP, Hart A, Jewell DP, Orchard TRet al., 2009, INFLAMMATORY BOWEL DISEASE IN CAUCASIAN AND UK SOUTH ASIAN PATIENTS: DIFFERENCE IN CLINICAL PHENOTYPE, Annual Meeting of the British-Society-of-Gastroenterology, Publisher: B M J PUBLISHING GROUP, Pages: A60-A60, ISSN: 0017-5749

Conference paper

Burn J, Bishop DT, Mecklin J-P, Macrae F, Moeslein G, Olschwang S, Bisgaard M-L, Ramesar R, Eccles D, Maher ER, Bertario L, Jarvinen HJ, Lindblom A, Evans DG, Lubinski J, Morrison PJ, Ho JWC, Vasen HFA, Side L, Thomas HJW, Scott RJ, Dunlop M, Barker G, Elliott F, Jass JR, Fodde R, Lynch HT, Mathers JCet al., 2008, Effect of Aspirin or Resistant Starch on Colorectal Neoplasia in the Lynch Syndrome, NEW ENGLAND JOURNAL OF MEDICINE, Vol: 359, Pages: 2567-2578, ISSN: 0028-4793

Journal article

Pittman AM, Webb E, Carvajal-Carmona L, Howarth K, Di Bernardo MC, Broderick P, Spain S, Walther A, Price A, Sullivan K, Twiss P, Fielding S, Rowan A, Jaeger E, Vijayakrishnan J, Chandler I, Penegar S, Qureshi M, Lubbe S, Domingo E, Kemp Z, Barclay E, Wood W, Martin L, Gorman M, Thomas H, Peto J, Bishop T, Gray R, Maher ER, Lucassen A, Kerr D, Evans GR, van Wezel T, Morreau H, Wijnen JT, Hopper JL, Southey MC, Giles GG, Severi G, Castellvi-Bel S, Ruiz-Ponte C, Carracedo A, Castells A, Foersti A, Hemminki K, Vodicka P, Naccarati A, Lipton L, Ho JWC, Cheng KK, Sham PC, Luk J, Agundez JAG, Ladero JM, de la Hoya M, Caldes T, Niitymaki I, Tuupanen S, Karhu A, Aaltonen LA, Cazier J-B, Tomlinson IPM, Houlston RSet al., 2008, Refinement of the basis and impact of common 11q23.1 variation to the risk of developing colorectal cancer, HUMAN MOLECULAR GENETICS, Vol: 17, Pages: 3720-3727, ISSN: 0964-6906

Journal article

East JE, Suzuki N, Bassett P, Stavrinidis M, Thomas HJW, Guenther T, Tekkis PP, Saunders BPet al., 2008, Narrow band imaging with magnification for the characterization of small and diminutive colonic polyps: pit pattern and vascular pattern intensity, ENDOSCOPY, Vol: 40, Pages: 811-817, ISSN: 0013-726X

Journal article

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