Cancer

There is a joint programme of cancer genetic research delivered by the University of Manchester and the Trust. We conduct translational research covering a number of inherited cancers and related syndromic conditions, from basic science through observational studies to clinical trials.

Gene discovery. Work has been carried out over a number of years and has been fundamental in discovering the genetic basis of a range of conditions including SMARCE1 meningioma predisposition (2013), and LZTR1 schwannomatosis (2015).
Clinical diagnostics. We have a widely recognized multidisciplinary team providing top level clinical and diagnostic services for patients with inherited cancer predisposing disorders including breast and ovarian cancer (BRCA1, BRCA2), inherited bowel cancer and polyposis syndromes (MSH2, MLH1, MSH6, APC, MYH1), inherited endocrine tumour conditions (MEN1, MEN2, vHL, SDHD, SDHB) and neurofibromatosis including NF1, NF2, schwannomatosis and SMARCE1 meningioma predisposition.
From discovery to translation. The translation of such discoveries into improved health provision is a major aspect of our work. Our team has developed next-generation sequencing (NGS) panels including BRCA1 and BRCA2, MSH2, MLH1, MSH6, APC, MYH1 and recently discovered genes SMARCE1, LZTR1 and SMARCB1, as well as offering highly sensitive RNA testing for NF1.
We work closely with patient groups especially the Hereditary Breast Cancer Help line, Lynch syndrome UK, Bowel cancer UK and Prevent Breast cancer to ensure our work is relevant to patient needs.

The team also provides direct support to the joint genetics and other specialist clinics including Risk reducing mastectomy MDTs at Wythenshawe (monthly), Gorlin MDTs at Christie (monthly) and endocrine MDTs.

Team Members

MCGM Clinical & Research

Name	Role
Professor D. Gareth Evans	Consultant in Genetics & Cancer Epidemiology
Dr Fiona Lalloo	Consultant in Medical Genetics
Dr Emma Woodward	Consultant in Medical Genetics
Helen Byers	Research Assistant (UoM)

MCGM Laboratory

Name	Role
Dr Andrew Wallace	Consultant Clinical Scientist
Helene Schlecht	Principal Clinical Scientist
Naomi Bowers	Clinical Scientist
Philip Smith	Clinical Scientist

University of Manchester

Name	Role
Professor William Newman	Consultant in Medical Genetics
Dr. Miriam Smith	Lecturer in Cancer Genomics

Patient Groups

Partner Institutions

Funding Partners

Research Projects

Predicting the risk of Cancer at Screening (PROCAS), NIHR 2009-15):
Predicting the risk of Cancer at Screening2 (PROCAS2), NIHR 2017-20):
FH02 breast screening study (Breast Cancer Now 2009-17)
CaPP3: a randomised double blind dose non-inferiority trial of aspirin in Lynch syndrome. (CR-UK 2014-)
Determination of uptake and response to preventive treatment with tamoxifen or raloxifene in women at moderate or high risk of breast cancer. (Breast Cancer Now 2014-18)
Development of Risk Prediction Models for Breast, Ovarian, Prostate and Other Cancers. (Cancer Research UK Programme Grant 2016-20)
Lynch Syndrome-Associated Endometrial Cancer: Prevention, Screening and Prognosis. MRC 2015-18
Biomedical research centre Manchester. NIHR programme. Cancer Prevention and Early Detection Evans Theme lead.
PROTECTOR (Preventing Ovarian Cancer through early Excision of Tubes and late Ovarian Removal) study Barts Charity 2017-20
MyPeBS (My Personal Breast Screening): Randomized Comparison Of Risk-Stratified versus Standard Breast Cancer Screening In European Women Aged 40-74. EU Horizon 2020 2018-2023
Epidemiological Study of BRCA1 and BRCA2 mutation carriers (EMBRACE) Cancer Research UK (2006-2023)

Publications

Ballinger ML, Best A, Mai PL, Khincha PP, Loud JT, Peters JA, Achatz MI, Chojniak R, Balieiro da Costa A, Santiago KM, Garber J, O’Neill AF, Eeles RA, Evans DG, Bleiker E, Sonke GS, Ruijs M, Loo C, Schiffman J, Naumer A, Kohlmann W, Strong LC, Bojadzieva J, Malkin D, Rednam SP, Stoffel EM, Koeppe E, Weitzel JN, Slavin TP, Nehoray B, Robson M, Walsh M, Manelli L, Villani A, Thomas DM, Savage SA. Baseline Surveillance in Li-Fraumeni Syndrome Using Whole-Body Magnetic Resonance Imaging: A Meta-analysis. JAMA Oncol. 2017 Aug 3. doi: 10.1001/jamaoncol.2017.1968. [Epub ahead of print]
Ryan NAJ, Morris J, Green K, Lalloo F, Woodward ER, Hill J, Crosbie EJ, Evans DG. Association of Mismatch Repair Mutation With Age at Cancer Onset in Lynch Syndrome: Implications for Stratified Surveillance Strategies. JAMA Oncol. 2017 Aug 3. doi: 10.1001/jamaoncol.2017.0619.
Evans DG, Harkness EF, Plaskocinska I, Wallace AJ, Clancy T, Woodward ER, Howell TA, Tischkowitz M, Lalloo F. Pathology update to the Manchester Scoring System based on testing in over 4000 families. J Med Genet. 2017; 54(10):674-681 May 10. pii: jmedgenet-2017-104584. doi: 10.1136/jmedgenet-2017
Ryan NA, Evans DG, Green K, Crosbie EJ. Pathological features and clinical behavior of Lynch syndrome-associated ovarian cancer. Gynecol Oncol. 2017 Jan 5. pii: S0090-8258(17)30042-2
Ferner RE, Shaw A, Evans DG, McAleer D, Halliday D, Parry A, Raymond FL, Durie-Gair J, Hanemann CO, Hornigold R, Axon P, Golding JF. Longitudinal evaluation of quality of life in 288 patients with neurofibromatosis 2. J Neurol. 2014; 261(5): 963-9 Mar 12.
Evans DG, Astley S, Stavrinos P, Harkness E, Donnelly LS, Dawe S, Jacob I, Harvie M, Cuzick J, Brentnall A, Wilson M, Harrison F, Payne K, Howell A. Improvement in risk prediction, early detection and prevention of breast cancer in the NHS Breast Screening Programme and family history clinics: a dual cohort study. Southampton (UK): NIHR Journals Library; 2016 Aug.
Møller P, Seppälä T, Bernstein I, Holinski-Feder E, Sala P, Evans DG, Lindblom A, Macrae F, Blanco I, Sijmons R, Jeffries J, Vasen H, Burn J, Nakken S, Hovig E, Rødland EA, Tharmaratnam K, de Vos Tot Nederveen Cappel WH, Hill J, Wijnen J, Jenkins M, Green K, Lalloo F, Sunde L, Mints M, Bertario L, Pineda M, Navarro M, Morak M, Renkonen-Sinisalo L, Frayling IM, Plazzer JP, Pylvanainen K, Genuardi M, Mecklin JP, Möslein G, Sampson JR, Capella G; Mallorca Group (http://mallorca-group.org). Incidence of and survival after subsequent cancers in carriers of pathogenic MMR variants with previous cancer: a report from the prospective Lynch syndrome database. Gut. 2016 Jun 3. pii: gutjnl-2016-311403. doi: 10.1136/gutjnl-2016-311403. [Epub ahead of print]
Byers H, Wallis Y, van Veen EM, Lalloo F, Reay K, Smith P, Wallace AJ, Bowers N, Newman WG, Evans DG. Sensitivity of BRCA1/2 testing in high-risk breast/ovarian/male breast cancer families: little contribution of comprehensive RNA/NGS panel testing. Eur J Hum Genet. 2016; 24(11):1591-1597
Evans DG, Lalloo F, Howell S, Verhoef S, Woodward ER, Howell A. Low prevalence of HER2 positivity amongst BRCA1 and BRCA2 mutation carriers and in primary BRCA screens. Breast Cancer Res Treat. 2016;155(3):597-601
Evans DG, Donnelly L, Astley S, Stavrinos P, Dawe S, Fox L, Harkness E, Sergeant J, Ingham S, Harvie M, Wilson M, Beetles U, Buchan I, Brentnall AR, French D, Cuzick J, Howell A. Identifying and informing women about their risk of breast cancer at screening: feedback in women at high and low risk in the first 50,000 women in the Predicting the Risk of Cancer at Screening (PROCAS) cohort study. Brit J Cancer 2016;114(9):1045-52.
Brentnall AR, Harkness E, Astley S, Donnelly L, Stavrinos P, Sampson S, Fox L, Sergeant J, Harvie M, Wilson M, Beetles U, Gadde S; Lim Y; Jain A; Bundred S; Barr N; Reece V; Howell A, Cuzick J, Evans DG. Mammographic density adds accuracy to both the Tyrer-Cuzick and Gail breast cancer risk models in a prospective UK screening cohort. Breast Cancer Res 2015; 17(1):147
Evans DG, Kotre CJ, Harkness E, Wilson M, Maxwell A, Howell A. No strong evidence for increased risk of breast cancer 8 to 26 years after multiple mammograms in their thirties in women at moderate and high familial risk. Brit J Radiol 2016; Mar;89(1059):20150960
Evans DG, Wisely J, Clancy T, Lalloo F, Wilson M, Johnson R, Duncan J, Barr L, Gandhi A, Howell A. Longer term effects of the Angelina Jolie effect: increased risk-reducing mastectomy rates in BRCA carriers and other high-risk women. Breast Cancer Res. 2015 Nov 25;17(1):143
Easton DF, Pharoah PD, Antoniou AC, Tischkowitz M, Tavtigian SV, Nathanson KL, Devilee P, Meindl A, Couch FJ, Southey M, Goldgar DE, Evans DG, Chenevix-Trench G, Rahman N, Robson M, Domchek SM, Foulkes WD. Gene-Panel Sequencing and the Prediction of Breast-Cancer Risk. N Engl J Med. 2015;372(23):2243-57
Møller P, Tharmaratnam K, Howell A, Stavrinos P, Sampson S, Wallace A, Maxwell AJ, Hagen AI, Evans DG. Tumour characteristics and survival in familial breast cancer prospectively diagnosed by annual mammography. Breast Cancer Res Treat. 2015; 152(1):87-94
Harkness EF, Barrow E, Newton K, Green K, Clancy T, Lalloo F, Hill J, Evans DG. Lynch syndrome caused by MLH1 mutations is associated with an increased risk of breast cancer: a cohort study. J Med Genet. 2015; 52(8):553-6
Smith MJ, Beetz C, Williams SG, Bhaskar SS, O’Sullivan J, Anderson B, Daly SB, Urquhart JE, Bholah Z, Oudit D, Cheesman E, Kelsey A, McCabe MG, Newman WG, Evans DG. Germline Mutations in SUFU Cause Gorlin Syndrome-Associated Childhood Medulloblastoma and Redefine the Risk Associated With PTCH1 Mutations. J Clin Oncol. 2014;32(36):4155-61 Nov 17. pii: JCO.2014.58.2569
Evans DG, Barwell J, Eccles DM, Collins A, Izatt L, Jacobs C, Donaldson A, Brady AF, Cuthbert A, Harrison R, Thomas S, Howell A, The FH02 Study Group, RGC teams, Miedzybrodzka Z, Murray A. The Angelina Jolie effect: How high celebrity profile can have a major impact on provision of cancer related services. Breast Cancer Research 2014:16 (5), 442
Newton K, Jorgensen NM, Wallace AJ, Buchanan DD, Lalloo F, McMahon RF, Hill J, Evans DG. Tumour MLH1 promoter region methylation testing is an effective prescreen for Lynch Syndrome (HNPCC). J Med Genet. 2014: 51(12):789-96
Evans DG, Brentnall AR, Harvie M, Dawe S, Sergeant JC, Stavrinos P, Astley SM, Wilson M, Ainsworth J, Cuzick J, Buchan I, Donnelly S, Howell A. Breast cancer risk in young women in the National Breast Screening Programme: implications for applying NICE guidelines for additional screening and chemoprevention. Cancer Prevention Research 2014; 7(10):993-1001
Evans DG, Harkness E, Lalloo F, Howell A. Long-term prospective clinical follow-up after BRCA1/2 presymptomatic testing: BRCA2 risks higher than in adjusted retrospective studies. J Med Genet. 2014;51(9):573-80.

Research

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