Research Biographies

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PROFESSOR MALCOLM DUNLOP, MD FRCS FMedSci FRSE

Colon Cancer Genetics Group and Academic Coloproctology

Head of Colon Cancer Genetics


Malcolm Dunlop

Contact Details

E-mail address: malcolm.dunlop@igmm.ed.ac.uk
Telephone: +44 (0)131 332 2471
Fax: +44 (0)131 467 8456
Address: MRC Human Genetics Unit MRC IGMM, University of Edinburgh Western General Hospital, Crewe Road, Edinburgh EH4 2XU
Research Programme: Colon Cancer Genetics and Chemoprevention

 


Research Areas

My primary research focus is on the genetic basis of colorectal cancer in order to shed new light on disease causation and to combat the disease through preventative approaches and early detection.  Genetic studies include investigation of the effect and contribution of known susceptibility alleles as well as to identify novel cancer predisposition genes. Genetics of colorectal cancer is a major theme of the group. We are engaged in population-based studies amounting to several thousand patients and controls from Scotland, cancer families and highly enriched patient groups with extreme phenotype colorectal cancer. We have undertaken a genome-wide scan for low penetrance alleles in colorectal cancer and this has led to identification of novel genes, and we are pursuing the basis of cancer susceptibility through functional studies for a number of these associations.


Cancer chemoprevention is another central theme of the group, focussed primarily on the effect of aspirin and other nonsteroidal anti-inflammatory drugs on NF-kappa-B signalling as a key mechanism of the anti-tumour effect of these agents. The work involves basic molecular and cell biology, animal studies and clinical translational studies in patients with rectal cancer, premalignant and also in patients at high risk of colorectal cancer due genetic predisposition.


Cancer screening in the general population and also in high risk groups is another focus of research activity. I was involved in the initiation of the UK Colorectal Cancer Screening Pilot Schemes as well as contributing to the assessment of outcome measures. I lead the UK initiative for developing surveillance guidelines for high risk genetic groups and published under the auspices of the British Society of Gastroenterology and the Association of Coloproctology of GB and Ireland.

 

Recent/Selected Publications


  • Kottgen A, Albrecht E, Teumer A, Vitart V, Krumsiek J, Hundertmark C, Pistis G, Ruggiero D, …….Hayward C, Zemunik T, Huffman J, ……...Hastie N, Balkau B,....Rivadeneira F, …………, Schurmann C, Budde K, Ernst F, Farrington SM, ....... …… Campbell H, Rudan I, ….., Deary IJ, …….Schipf S, Dunlop MG, Tonjes A, Ripatti S, Soranzo N, Toniolo D, Chasman DI, .....Caulfield M, Bochud M, and Gieger C. Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. Nat. Genet. 45: 145-154. 2013
    PubMed Abstract
  • Davies JL, Cazier JB, Dunlop MG, Houlston RS, Tomlinson IP, and Holmes CC. A novel test for gene-ancestry interactions in genome-wide association data. PLoS. One. 7: e48687. 2012
    PubMed Abstract
  • Theodoratou E, Montazeri Z, Hawken S, Allum GC, Gong J, Tait V, Kirac I, Tazari M, Farrington SM, Demarsh A, Zgaga L, Landry D, Benson HE, Read SH, Rudan I, Tenesa A, Dunlop MG, Campbell H, Little J: Systematic meta-analyses and field synopsis of genetic association studies in colorectal cancer. J Natl Cancer Inst 104:1433-1457, 2012.
    PubMed Abstract
  • Kinnersley B, Migliorini G, Broderick P, Whiffin N, Dobbins SE, Casey G, Hopper J, Sieber O, Lipton L, Kerr DJ, Dunlop MG, Tomlinson IP, Houlston RS: The TERT variant rs2736100 is associated with colorectal cancer risk. Br J Cancer 107:1001-1008, 2012.
    PubMed Abstract
  • Zgaga L, Theodoratou E, Kyle J, Farrington SM, Agakov F, Tenesa A, Walker M, McNeill G, Wright AF, Rudan I, Dunlop MG, Campbell H: The association of dietary intake of purine-rich vegetables, sugar-sweetened beverages and dairy with plasma urate, in a cross-sectional study.
    PLoS One 7:e38123, 2012.
    PubMed Abstract
  • Theodoratou E, Palmer T, Zgaga L, Farrington SM, McKeigue P, Din FV, Tenesa A, Davey-Smith G, Dunlop MG, Campbell H: Instrumental variable estimation of the causal effect of plasma 25-hydroxy-vitamin d on colorectal cancer risk: a mendelian randomization analysis
    PLoS One 7:e37662, 2012.
    PubMed Abstract
  • Hingorani AD, Casas JP: The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis
    Lancet 379:1214-1224, 2012.
    PubMed Abstract
  • Dunlop MG, Tenesa A, Farrington SM, Ballereau S, Brewster DH, Koessler T, Pharoah P, Schafmayer C, Hampe J, Volzke H, Chang-Claude J, Hoffmeister M, Brenner H, von HS, Picelli S, Lindblom A, Jenkins MA, Hopper JL, Casey G, Duggan D, Newcomb PA, Abuli A, Bessa X, Ruiz-Ponte C, Castellvi-Bel S, Niittymaki I, Tuupanen S, Karhu A, Aaltonen L, Zanke B, Hudson T, Gallinger S, Barclay E, Martin L, Gorman M, Carvajal-Carmona L, Walther A, Kerr D, Lubbe S, Broderick P, Chandler I, Pittman A, Penegar S, Campbell H, Tomlinson I, Houlston RS: Cumulative impact of common genetic variants and other risk factors on colorectal cancer risk in 42 103 individuals
    Gut 2012.
    PubMed Abstract
  • Dunlop MG, Dobbins SE, Farrington SM, Jones AM, Palles C, Whiffin N, Tenesa A, Spain S, Broderick P, Ooi LY, Domingo E, Smillie C, Henrion M, Frampton M, Martin L, Grimes G, Gorman M, Semple C, Ma YP, Barclay E, Prendergast J, Polychronis A, ..................PD, Potter V, Jephcott C, McAdam K, Wrigley J, Osborne R, Muthuramalingam S, O'Callaghan A, Bridgewater J, Melcher L, Braconi C, Geh JI, Palmer D, Narayana P, Steven N, Gaya A: Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk
    Nat Genet 2012.
    PubMed Abstract
  • Din FV, Valanciute A, Houde VP, Zibrova D, Green KA, Sakamoto K, Alessi DR, Dunlop MG: Aspirin Inhibits mTOR Signaling, Activates AMP-Activated Protein Kinase, and Induces Autophagy in Colorectal Cancer Cells
    Gastroenterology 142:1504-1515, 2012.
    PubMed Abstract
  • Turnbull CL, Bacon AL, Dunlop MG, Farrington SM: In vitro stability of APC gene sequences and the influence of DNA repair status
    Mutagenesis 27:233-238, 2012
    PubMed Abstract
  • Tomlinson IP, Houlston RS, Montgomery GW, Sieber OM, Dunlop MG: Investigation of the effects of DNA repair gene polymorphisms on the risk of colorectal cancer. Mutagenesis 27:219-223, 2012.
    PubMed Abstract
  • Spain SL, Carvajal-Carmona LG, Howarth KM, Jones AM, Su Z, Cazier JB, Williams J, Aaltonen LA, Pharoah P, Kerr DJ, Cheadle J, Li L, Casey G, Vodicka P, Sieber O, Lipton L, Gibbs P, Martin NG, Montgomery GW, Young J, Baird PN, Morreau H, van WT, Ruiz-Ponte C, Fernandez-Rozadilla C, Carracedo A, Castells A, Castellvi-Bel S, Dunlop M, Houlston RS, Tomlinson IP: Refinement of the associations between risk of colorectal cancer and polymorphisms on chromosomes 1q41 and 12q13.13 Hum Mol Genet 21:934-946, 2012. PubMed Abstract
  • Brush J, Boyd K, Chappell F, Crawford F, Dozier M, Fenwick E, Glanville J, McIntosh H, Renehan A, Weller D, Dunlop M: The value of FDG positron emission tomography/computerised tomography (PET/CT) in pre-operative staging of colorectal cancer: a systematic review and economic evaluation
    Health Technol Assess 15:1-iv, 2011.
    PubMed Abstract
  • Zgaga L, Theodoratou E, Farrington SM, Agakov F, Tenesa A, Walker M, Knox S, Wallace AM, Cetnarskyj R, McNeill G, Kyle J, Porteous ME, Dunlop MG, Campbell H: Diet, environmental factors, and lifestyle underlie the high prevalence of vitamin D deficiency in healthy adults in Scotland, and supplementation reduces the proportion that are severely deficient. J Nutr 141:1535-1542, 2011.
    PubMed Abstract
  • Aldhous MC, Soo K, Stark LA, Ulanicka AA, Easterbrook JE, Dunlop MG, Satsangi J: Cigarette smoke extract (CSE) delays NOD2 expression and affects NOD2/RIPK2 interactions in intestinal epithelial cells PLoS One 6:e24715, 2011PubMed Abstract
  • Burn, S.F.; Webb, A.; Berry, R.L.; Davies, J.A.; Ferrer-Vaquer, A.; Hadjantonakis, A.K.; Hastie, N.D. and Hohenstein, P. Calcium/NFAT signalling promotes early nephrogenesis. Dev.Biol. 352(2):288-98, 2011 PubMed Abstract
  • Tomlinson IP, Carvajal-Carmona LG, Dobbins SE, Tenesa A, Jones AM, Howarth K, Palles C, Broderick P, Jaeger EE, Farrington S, Lewis A, Prendergast JG, Pittman AM, Theodoratou E, Olver B, Walker M, Penegar S, Barclay E, Whiffin N, Martin L, Ballereau S, Lloyd A, Gorman M, Lubbe S, Howie B, Marchini J, Ruiz-Ponte C, Fernandez-Rozadilla C, Castells A, Carracedo A, Castellvi-Bel S, Duggan D, Conti D, Cazier JB, Campbell H, Sieber O, Lipton L, Gibbs P, Martin NG, Montgomery GW, Young J, Baird PN, Gallinger S, Newcomb P, Hopper J, Jenkins MA, Aaltonen LA, Kerr DJ, Cheadle J, Pharoah P, Casey G, Houlston RS, Dunlop MG: Multiple common susceptibility variants near BMP pathway loci GREM1, BMP4, and BMP2 explain part of the missing heritability of colorectal cancer
    9. PLoS Genet 7:e1002105, 2011. PubMed Abstract

Selected Recent Chemoprevention Papers

  1. Burn, J.; Bishop, D.T.; Mecklin, J.P.; Macrae, F.; Moslein, G.; Olschwang, S.; Bisgaard, M.L.; Ramesar, R.; Eccles, D.; Maher, E.R.; Bertario, L.; Jarvinen, H.J.; Lindblom, A.; Evans, D.G.; Lubinski, J.; Morrison, P.J.; Ho, J.W.; Vasen, H.F.; Side, L.; Thomas, H.J.; Scott, R.J.; Dunlop, M.; Barker, G.; Elliott, F.; Jass, J.R.; Fodde, R.; Lynch, H.T. and Mathers, J.C. Effect of aspirin or resistant starch on colorectal neoplasia in the Lynch syndrome. N Engl J Med 359(24):2567-2578, 2008 PubMed Abstract
  2. Loveridge, C.J.; MacDonald, A.D.; Thoms, H.C.; Dunlop, M.G. and Stark, L.A. The proapoptotic effects of sulindac, sulindac sulfone and indomethacin are mediated by nucleolar translocation of the RelA(p65) subunit of NF-kappaB. Oncogene 27(18):2648-2655, 2008 PubMed Abstract
  3. Thoms, H.C.; Dunlop, M.G. and Stark, L.A. CDK4 inhibitors and apoptosis: a novel mechanism requiring nucleolar targeting of RelA. Cell Cycle 6(11):1293-1297, 2007 PubMed Abstract
  4. Thoms, H.C.; Dunlop, M.G. and Stark, L.A. p38-mediated inactivation of cyclin D1/cyclin-dependent kinase 4 stimulates nucleolar translocation of RelA and apoptosis in colorectal cancer cells. Cancer Res 67(4):1660-1669, 2007 PubMed Abstract
  5. Stark, L.A.; Reid, K.; Sansom, O.J.; Din, F.V.; Guichard, S.; Mayer, I.; Jodrell, D.I.; Clarke, A.R. and Dunlop, M.G. Aspirin activates the NF-{kappa}B signalling pathway and induces apoptosis in intestinal neoplasia in two in vivo models of human colorectal cancer. Carcinogenesis 28(5):968-976, 2007 PubMed Abstract
  6. Stark, L.A. and Dunlop, M.G. Nucleolar sequestration of RelA (p65) regulates NF-kappaB-driven transcription and apoptosis. Mol Cell Biol 25(14):5985-6004, 2005 PubMed Abstract