Imperial College London

DrKevinMonahan

Faculty of MedicineDepartment of Surgery & Cancer

Honorary Clinical Senior Lecturer
 
 
 
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k.monahan Website

 
 
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Location

 

CRUKSt Marks HospitalNorthwick Park and St Marks Site

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Summary

 

Publications

Publication Type
Year
to

120 results found

Monahan KJ, Davies MM, Abulafi M, Banerjea A, Nicholson BD, Arasaradnam R, Barker N, Benton S, Booth R, Burling D, Carten RV, D'Souza N, East JE, Kleijnen J, Machesney M, Pettman M, Pipe J, Saker L, Sharp L, Stephenson J, Steele RJCet al., 2022, Faecal immunochemical testing (FIT) in patients with signs or symptoms of suspected colorectal cancer (CRC): a joint guideline from the Association of Coloproctology of Great Britain and Ireland (ACPGBI) and the British Society of Gastroenterology (BSG), GUT, ISSN: 0017-5749

Journal article

Woodfield G, Belluomo I, Laponogov I, Veselkov K, COBRA1 Working Group, Cross AJ, Hanna GB, Boshier PR, Lin GP, Myridakis A, Ayrton O, Španěl P, Vidal-Diez A, Romano A, Martin J, Marelli L, Groves C, Monahan K, Kontovounisios C, Saunders BPet al., 2022, Diagnostic performance of a non-invasive breath test for colorectal cancer: COBRA1 study, Gastroenterology, ISSN: 0016-5085

Journal article

Edwards P, Monahan KJ, 2022, Diagnosis and management of Lynch syndrome, Frontline Gastroenterology, Vol: 13, Pages: e80-e87, ISSN: 2041-4137

Lynch syndrome (LS) is a dominantly inherited cancer susceptibility syndrome defined by presence of pathogenic variants in DNA mismatch repair genes MLH1, MSH2, MSH6 and PMS2, or in deletions of the EPCAM gene. Although LS is present in about 1 in 400 people in the UK, it estimated that only 5% of people with this condition are aware of the diagnosis. Therefore, testing for LS in all new diagnoses of colorectal or endometrial cancers is now recommended in the UK, and gastroenterologists can offer ‘mainstreamed’ genetic testing for LS to patients with cancer. Because LS results in a high lifetime risk of colorectal, endometrial, gastric, ovarian, hepatobiliary, brain and other cancers, the lifelong care of affected individuals and their families requires a coordinated multidisciplinary approach. Interventions such as high-quality 2-yearly colonoscopy, prophylactic gynaecological surgery, and aspirin are proven to prevent and facilitate early diagnosis and prevention of cancers in this population, and improve patient outcomes. Recently, an appreciation of the mechanism of carcinogenesis in LS-associated cancers has contributed to the development of novel therapeutic and diagnostic approaches, with a gene-specific approach to disease management, with potential cancer-preventing vaccines in development. An adaptive approach to surgical or oncological management of LS-related cancers may be considered, including an important role for novel checkpoint inhibitor immunotherapy in locally advanced or metastatic disease. Therefore, a personalised approach to lifelong gene-specific management for people with LS provides many opportunities for cancer prevention and treatment which we outline in this review.

Journal article

Sun M, Moquet J, Ellender M, Bouffler S, Badie C, Baldwin-Cleland R, Monahan K, Latchford A, Lloyd D, Clark S, Anyamene NA, Ainsbury E, Burling Det al., 2022, Potential risks associated with the use of ionizing radiation for imaging and treatment of colorectal cancer in Lynch syndrome patients, Familial Cancer, ISSN: 1389-9600

The aim of this review is to investigate the literature pertaining to the potential risks of low-dose ionizing radiation to Lynch syndrome patients by use of computed tomography (CT), either diagnostic CT colonography (CTC), standard staging CT or CT surveillance. Furthermore, this review explores the potential risks of using radiotherapy for treatment of rectal cancer in these patients. No data or longitudinal observational studies of the impact of radiation exposure on humans with Lynch syndrome were identified. Limited experimental studies utilizing cell lines and primary cells exposed to both low and high radiation doses have been carried out to help determine radio-sensitivity associated with DNA mismatch repair gene deficiency, the defining feature of Lynch syndrome. On balance, these studies suggest that mismatch repair deficient cells may be relatively radio-resistant (particularly for low dose rate exposures) with higher mutation rates, albeit no firm conclusions can be drawn. Mouse model studies, though, showed an increased risk of developing colorectal tumors in mismatch repair deficient mice exposed to radiation doses around 2 Gy. With appropriate ethical approval, further studies investigating radiation risks associated with CT imaging and radiotherapy relevant doses using cells/tissues derived from confirmed Lynch patients or genetically modified animal models are urgently required for future clinical guidance.

Journal article

Ahmad A, Moorghen M, Wilson A, Stasinos I, Haycock A, Humphries A, Monahan K, Suzuki N, Thomas-Gibson S, Vance M, Thiruvilangam K, Dhillon A, Saunders BPet al., 2022, Implementation of optical diagnosis with a 'resect and discard strategy' in clinical practice: DISCARD3 study., Gastrointest Endosc

BACKGROUND AND AIMS: Optical diagnosis (OD) of polyps can be performed with advanced endoscopic imaging. For high confidence diagnoses, a "resect and discard" strategy could offer significant histopathology time and cost savings. The implementation threshold is a ≥90% OD-histology surveillance interval concordance. AIMS: assess OD learning curve and feasibility of "resect and discard" strategy for ≤5mm and <10mm polyps in a bowel cancer screening setting. METHODS: In this prospective feasibility study, 8 bowel cancer screening endoscopists completed a validated OD training module and performed procedures. All <10mm consecutive polyps had white-light and narrow-band images taken and were given high/low confidence diagnoses until 120 high confidence ≤5mm polyp diagnoses had been performed. All polyps had standard histology. High confidence OD error underwent root cause analysis. Histology and OD-derived surveillance intervals were calculated. RESULTS: 565 patients were invited with 525 patients included. 1560 <10mm polyps underwent OD and were resected and retrieved (1329 ≤5mm and 231 6-9mm). There were no <10mm polyp cancers. High confidence OD was accurate in 81.5% of ≤5mm and 92.8% of 6-9mm polyps. Sensitivity for OD of a ≤5mm adenoma was 93.0% with a PPV of 90.8%. OD-histology surveillance interval concordance for ≤5mm OD was 91.3% (209/229), 98.3% (225/229) and 98.7% (226/229) for US multi-society task force, ESGE and BSG guidelines respectively. CONCLUSIONS: A "resect and discard" strategy for high confidence ≤5mm polyp OD, in a group of bowel cancer screening colonoscopists, is feasible and safe with performance exceeding the 90% surveillance interval concordance required for implementation in clinical practice.

Journal article

Lincoln AG, Benton SC, Sasieni P, Monahan KJet al., 2022, Risk-stratified FIT for urgent colonoscopy in Lynch syndrome: A clinical service throughout the COVID-19 pandemic., Journal of Clinical Oncology, Vol: 40, Pages: 10606-10606, ISSN: 0732-183X

<jats:p> 10606 </jats:p><jats:p> Background: Lynch syndrome (LS) is an inherited disorder characterized by pathogenic variants within mismatch repair genes resulting in an increased risk of colorectal cancer (CRC). In England, the fecal immunochemical test for Haemoglobin (FIT) is currently used in non-LS symptomatic and screening populations to guide subsequent colonoscopy. Herein, we report results from a national emergency clinical service implemented during the COVID-19 pandemic which used FIT to prioritize colonoscopy in LS patients while endoscopy services were limited. Methods: Regional genetic and endoscopy services across England were invited to participate. Patient eligibility was determined by 1) Diagnosis of Lynch Syndrome 2) Planned colonoscopic surveillance between 1 March 2020 and 31 March 2021. Requests for FIT testing from participating NHS Trusts were sent to the NHS Bowel Cancer Screening South of England Hub’s Research Laboratory in Surrey. The Hub sent patients a FIT kit (OC-Sensor™ (Eiken, Japan)), instructions for use, a questionnaire, and a pre-paid return envelope. Lab reports with feecal haemoglobin (f-Hb) results were returned electronically for clinical action. LS patients were risk-stratified for colonoscopy based upon the following f-Hb thresholds: (1) f-Hb ≥10µg of Haemoglobin (Hb)/g (µg/g) faeces: triaged for colonoscopy via an urgent two-week wait (2WW) pathway, (2) f-Hb ≤10µg/g: schedule patients for colonoscopy within 6-12 weeks, where local endoscopy service availability permits. Results: Fifteen centers across England participated in the clinical service from 9<jats:sup>th</jats:sup> June 2020 to 31<jats:sup>st</jats:sup> March 2021. An uptake rate of 64% was observed from this cohort (375/588 invites), though 21 cases were removed from analysis due to repeat FITs, insufficient sample, missing clinical data, or FIT completed after colonoscopy. Of the re

Journal article

Morley O, Mavrou A, Pawa N, Monahan Ket al., 2022, P229 Post-colorectal cancer resection colonoscopy: factors associated with compliance, Abstracts of the BSG Annual Meeting, 20–23 June 2022, Publisher: BMJ Publishing Group Ltd and British Society of Gastroenterology

Conference paper

Ahmad A, Moorghen M, Wilson A, Stasinos I, Haycock A, Humphries A, Monahan K, Suzuki N, Thomas-Gibson S, Vance M, Thiruvilangam K, Dhillon A, Saunders BPet al., 2022, O52 Optical diagnosis of polyps &lt;10mm and impact on surveillance interval (DISCARD3), Abstracts of the BSG Annual Meeting, 20–23 June 2022, Publisher: BMJ Publishing Group Ltd and British Society of Gastroenterology

Conference paper

Ahmad A, Moorghen M, Wilson A, Stasinos I, Haycock A, Humphries A, Monahan K, Suzuki N, Thomas-Gibson S, Vance M, Thiruvilangam K, Dhillon A, Saunders BPet al., 2022, P132 Learning curve for optical diagnosis of small polyps at screening colonoscopy (DISCARD3), Abstracts of the BSG Annual Meeting, 20–23 June 2022, Publisher: BMJ Publishing Group Ltd and British Society of Gastroenterology

Conference paper

Perea J, Corchete LA, Monahan KJ, Spinelli A, Foppa C, Miranda NFD, Abdulrahman M, Palles C, Curley HM, Balaguer F, Alvarez MDLAD, Marti-Gallostra M, Verdaguer M, Vivas A, Latchford A, Faiz O, Pawa N, Aseem R, Tarnowski W, Szczepkowski M, Borycka-Kiciak K, Makkai-Popa S-T, Azagra JS, Garcia-Olmo D, Gonzalez-Sarmiento R, Holowatyj Aet al., 2022, 1144: EARLY-ONSET COLORECTAL CANCER: GEOGRAPHICAL DISPARITIES ACCORDING TO PHENOTYPE, Gastroenterology, Vol: 162, Pages: S-269, ISSN: 0016-5085

Journal article

Loong L, Cubuk C, Choi S, Allen S, Torr B, Garrett A, Loveday C, Durkie M, Callaway A, Burghel GJ, Drummond J, Robinson R, Berry IR, Wallace A, Eccles DM, Tischkowitz M, Ellard S, Ware JS, Hanson H, Turnbull C, CanVIG-UKet al., 2022, Quantifying prediction of pathogenicity for within-codon concordance (PM5) using 7541 functional classifications of BRCA1 and MSH2 missense variants, Genetics in Medicine, Vol: 24, Pages: 552-563, ISSN: 1098-3600

PURPOSE: Conditions and thresholds applied for evidence weighting of within-codon concordance (PM5) for pathogenicity vary widely between laboratories and expert groups. Because of the sparseness of available clinical classifications, there is little evidence for variation in practice. METHODS: We used as a truthset 7541 dichotomous functional classifications of BRCA1 and MSH2, spanning 311 codons of BRCA1 and 918 codons of MSH2, generated from large-scale functional assays that have been shown to correlate excellently with clinical classifications. We assessed PM5 at 5 stringencies with incorporation of 8 in silico tools. For each analysis, we quantified a positive likelihood ratio (pLR, true positive rate/false positive rate), the predictive value of PM5-lookup in ClinVar compared with the functional truthset. RESULTS: pLR was 16.3 (10.6-24.9) for variants for which there was exactly 1 additional colocated deleterious variant on ClinVar, and the variant under examination was equally or more damaging when analyzed using BLOSUM62. pLR was 71.5 (37.8-135.3) for variants for which there were 2 or more colocated deleterious ClinVar variants, and the variant under examination was equally or more damaging than at least 1 colocated variant when analyzed using BLOSUM62. CONCLUSION: These analyses support the graded use of PM5, with potential to use it at higher evidence weighting where more stringent criteria are met.

Journal article

Lincoln A, Benton SC, Sasieni P, Monahan KJet al., 2022, PTH-27 Risk-stratified FIT for urgent colonoscopy in Lynch Syndrome: A clinical service throughout the COVID-19 pandemic (vol 70, pg A184, 2021), GUT, Vol: 71, Pages: E3-E3, ISSN: 0017-5749

Journal article

Llach J, Pellisé M, Monahan K, 2022, Lynch syndrome; towards more personalized management?, Best Practice and Research: Clinical Gastroenterology, ISSN: 1521-6918

Lynch syndrome is the most common inherited cause of colorectal (lifetime risk up to 70%) and endometrial cancer. The diagnosis of Lynch syndrome facilitates preventive measures aimed at reducing the incidence and mortality of cancer. Colonoscopic surveillance for colorectal cancer, aspirin, and prophylactic hysterectomy and bilateral salpo-oopherectomy for endometrial and/or ovarian cancer have demonstrated to effectively reduce cancer mortality in this population. However, the lifetime risk of each cancer in people with Lynch syndrome is gene-specific and may be modified by environmental factors. Furthermore, the benefits of surveillance strategies need to be balanced against the risk of over-diagnosis and be supported by evidence of improved outcomes from cancer diagnosis in surveillance. Therefore, people with Lynch syndrome may benefit from a personalized management approach.

Journal article

Ahmad A, Wilson A, Thomas-Gibson S, Suzuki N, Humphries A, Haycock A, Monahan K, Vance M, Dhillon A, Saunders Bet al., 2021, PATIENT ACCEPTABILITY OF DIMINUTIVE POLYP OPTICAL DIAGNOSIS WITH RESECT AND DISCARD STRATEGY IN SCREENING COLONOSCOPY, Annual Meeting of the British-Society-of-Gastroenterology (BSG), Publisher: BMJ PUBLISHING GROUP, Pages: A48-A49, ISSN: 0017-5749

Conference paper

Ahmad A, Wilson A, Thomas-Gibson S, Suzuki N, Humphries A, Haycock A, Monahan K, Vance M, Dhillon A, Saunders Bet al., 2021, LEARNING CURVE OF OPTICAL DIAGNOSIS WITH A RESECT AND DISCARD STRATEGY FOR SCREENING COLONOSCOPY, Annual Meeting of the British-Society-of-Gastroenterology (BSG), Publisher: BMJ PUBLISHING GROUP, Pages: A48-A48, ISSN: 0017-5749

Conference paper

Ahmad A, Wilson A, Moorghen M, Dhillon A, Thomas-Gibson S, Suzuki N, Humphries A, Haycock A, Monahan K, Vance M, Saunders Bet al., 2021, OPTICAL DIAGNOSIS OF SMALL POLYPS AT COLONOSCOPY VERSUS HISTOPATHOLOGY: MOVING TOWARDS A NEW GOLD STANDARD?, Publisher: BMJ PUBLISHING GROUP, Pages: A28-A29, ISSN: 0017-5749

Conference paper

Mak S, Latchford A, Hawkins M, Cuthill V, Thomas H, Clark S, Monahan Ket al., 2021, DIAGNOSTIC YIELD OF CONSTITUTIONAL GENETIC TESTING IN PATIENTS WITH MULTIPLE COLORECTAL ADENOMAS (MCRA), Publisher: BMJ PUBLISHING GROUP, Pages: A16-A17, ISSN: 0017-5749

Conference paper

Ahmad A, Wilson A, Dhillon A, Thomas-Gibson S, Suzuki N, Humphries A, Haycock A, Monahan K, Vance M, Saunders Bet al., 2021, SMALL POLYPS AT COLONOSCOPY AND THE NICE CLASSIFICATION: LIKELY CAUSES OF OPTICAL DIAGNOSIS ERROR, Annual Meeting of the British-Society-of-Gastroenterology (BSG), Publisher: BMJ PUBLISHING GROUP, Pages: A47-A48, ISSN: 0017-5749

Conference paper

Ahmad A, Wilson A, Dhillon A, Thomas-Gibson S, Suzuki N, Humphries A, Haycock A, Monahan K, Vance M, Saunders Bet al., 2021, NO SURVEILLANCE INTERVAL CHANGE WITH OPTICAL DIAGNOSIS OF SMALL POLYPS DURING BOWEL CANCER SCREENING COLONOSCOPY, Annual Meeting of the British-Society-of-Gastroenterology (BSG), Publisher: BMJ PUBLISHING GROUP, Pages: A51-A52, ISSN: 0017-5749

Conference paper

Aggarwal N, Quaglia A, McPhail MJW, Monahan KJet al., 2021, Systematic review and meta-analysis of tumour microsatellite-instability status as a predictor of response to fluorouracil-based adjuvant chemotherapy in colorectal cancer, INTERNATIONAL JOURNAL OF COLORECTAL DISEASE, Vol: 37, Pages: 35-46, ISSN: 0179-1958

Journal article

Ryan NAJ, Snowsill T, McKenzie E, Monahan KJ, Nebgen Det al., 2021, Should women with Lynch syndrome be offered gynaecological cancer surveillance?, BMJ, Vol: 374, Pages: 1-4, ISSN: 1759-2151

Journal article

Alexander J, Johnston B, Smith T, Yong KK, Marshall S, Fawkes J, Martin J, Seward E, Saunders B, Monahan Ket al., 2021, Low referral rates for genetic assessment of patients with multiple adenomas in United Kingdom Bowel Cancer Screening Programmes, Diseases of the Colon and Rectum, Vol: 64, Pages: 1058-1063, ISSN: 0012-3706

Background:Approximately one in twenty cases of colorectal cancer are caused by monogenic syndromes. Published guidelines recommend that patients with ten or more adenomas be referred for genetic testing, based on evidence that colorectal cancer risk is associated with adenoma multiplicity. Objective:The aim of this study was to determine adherence to guidelines on referral for genetic screening in patients with ten or more adenomas.Design:A cross-sectional study was performed of prospectively collected data from the United Kingdom Bowel Cancer Screening Program between May 2007 & June 2018. Only histologically confirmed adenomas were included. Clinicopathological data were recorded from patient records and referrals to clinical genetics services were ascertained. Setting:Data were obtained from three centres in London, United Kingdom.Patients:A total of 17,450 subjects underwent colonoscopy following an abnormal faecal occult blood test. Main outcome measures:We quantified patients with ten or more adenomas and the proportion referred for genetic screening.Results:The adenoma detection rate was 50.6% amongst 17,450 patients who underwent colonoscopy (8,831 had one or more adenomas). 347 patients (2.0%) had 10 or more adenomas. Patients with 10 or more adenomas were more likely to be male than those with less than 10 adenomas (76.9% vs. 53.4%; p<0.0001). A family history was collected in 37.8% of the multiple adenoma population. Of 347 patients with 10 or more adenomas, 28 (8.1%) were referred for genetic assessment.Limitations:All three screening centres were in a single city. No genetic outcome data were available to permit analysis of actual rates of inherited cancer syndromes in this population.Conclusions:In this study, almost one in fifty patients had ten or more adenomas. Despite guidelines advising genetic testing in this group, referral rates are low. A referral pathway and management strategies should be established to address this patient popula

Journal article

D'Souza N, Monahan K, Benton SC, Wilde L, Abulafi Met al., 2021, Finding the needle in the haystack: the diagnostic accuracy of the faecal immunochemical test for colorectal cancer in younger symptomatic patients, Colorectal Disease, Vol: 23, Pages: 2539-2549, ISSN: 1462-8910

AimDetection of early onset colorectal cancer is challenging, and remains a rare diagnosis amongst younger people with gastrointestinal symptoms. We investigated whether faecal immunochemical testing (FIT) could identify younger patients at higher risk of colorectal cancer or serious bowel disease including colorectal cancer, inflammatory bowel disease or advanced adenomas.MethodsA subgroup analysis was performed of symptomatic patients under 50 years of age (<50) from the NICE FIT study, a multicentre, prospective diagnostic accuracy study of FIT conducted between October 2017 and December 2019. The diagnostic accuracy of FIT for colorectal cancer and serious bowel disease was investigated in younger patients at different faecal haemoglobin (f-Hb) cut-offs of 2, 10 and 150 µg blood/g faeces (µg/g).ResultsEarly onset colorectal cancer was diagnosed in 1.5% (16/1103) of younger symptomatic patients. The sensitivity of FIT for younger patients aged <50 was 87.5% (95% CI 61.7%–98.4%), 81.3% (54.4%–96.0%) and 68.8% (41.3%–89.0%) at f-Hb cut-offs of 2, 10 and 150 µg/g, respectively. The positive predictive value for colorectal cancer increased from 4.2% (2.3%–6.9%) to 11.5% (5.9%–19.6%) at cut-offs of 2 and 150 µg/g, while the positive predictive value for serious bowel disease increased from 31.3% (26.3%–36.5%) to 65.6% (55.2%–75.0%) at the same cut-offs. The negative predictive value of FIT for colorectal cancer remained above 99.5% at all cut-offs.ConclusionDetectable f-Hb on FIT in symptomatic younger patients may indicate referral for investigation of colorectal cancer and serious bowel disease.

Journal article

Win AK, Dowty JG, Reece JC, Lee G, Templeton AS, Plazzer J-P, Buchanan DD, Akagi K, Aksoy S, Alonso A, Alvarez K, Amor DJ, Ankathil R, Aretz S, Arnold JL, Aronson M, Austin R, Backman A-S, Bajwa-ten Broeke SW, Barca-Tierno V, Barwell J, Bernstein I, Berthet P, Betz B, Bignon Y-J, Boisjoli T, Bonadona V, Briollais L, Brunet J, Bucksch K, Buecher B, Buettner R, Burn J, Caldés T, Capella G, Caron O, Casey G, Chew MH, Choi Y-H, Church J, Clendenning M, Colas C, Cops EJ, Coupier I, Cruz-Correa M, de la Chapelle A, de Wind N, Dębniak T, Della Valle A, Delnatte C, Dhooge M, Dominguez-Valentin M, Drouet Y, Duijkers FA, Engel C, Esperon P, Evans DG, Falcón de Vargas A, Figueiredo JC, Foulkes W, Fourme E, Frebourg T, Gallinger S, Garre P, Genuardi M, Gerdes A-M, Gima LM, Giraud S, Goodwin A, Görgens H, Green K, Guillem J, Guillén-Ponce C, Guimbaud R, Guindalini RSC, Half EE, Hall MJ, Hampel H, Hansen TVO, Heinimann K, Hes FJ, Hill J, Ho JWC, Holinski-Feder E, Hoogerbrugge N, Hüneburg R, Huntley V, James PA, Jensen UB, John T, Juhari WKW, Kalady M, Kastrinos F, Kloor M, Kohonen-Corish MRJ, Krogh LN, Kupfer SS, Ladabaum U, Lagerstedt-Robinson K, Lalloo F, Lasset C, Latchford A, Laurent-Puig P, Lautrup CK, Leggett BA, Lejeune S, LeMarchand L, Ligtenberg M, Lindor N, Loeffler M, Longy M, Lopez F, Lowery J, Lubiński J, Lucassen AM, Lynch PM, Malińska K, Matsubara N, Mecklin J-P, Møller P, Monahan K, Morrison PJ, Nattermann J, Navarro M, Neffa F, Neklason D, Newcomb PA, Ngeow J, Nichols C, Nielsen M, Nixon DM, Nogues C, Okkels H, Olschwang S, Pachter N, Pai RK, Palmero EI, Pande M, Parry S, Patel SG, Pearlman R, Perne C, Pineda M, Poplawski NK, Pylvänäinen K, Qiu J, Rahner N, Ramesar R, Rasmussen LJ, Redler S, Reis RM, Ricciardiello L, Rogoża-Janiszewska E, Rosty C, Samadder NJ, Sampson JR, Schackert HK, Schmiegel W, Schulmann K, Schuster H, Scott R, Senter L, Seppälä TT, Shtoyerman R, Sijmons RH, Snyder C, Solomon IB, Soto JL, Southey MC, Spigelman A, Spirandelli F, Spurdle AB, Stet al., 2021, Variation in the risk of colorectal cancer in families with Lynch syndrome: a retrospective cohort study, The Lancet Oncology, ISSN: 1470-2045

BackgroundExisting clinical practice guidelines for carriers of pathogenic variants of DNA mismatch repair genes (Lynch syndrome) are based on the mean age-specific cumulative risk (penetrance) of colorectal cancer for all carriers of pathogenic variants in the same gene. We aimed to estimate the variation in the penetrance of colorectal cancer between carriers of pathogenic variants in the same gene by sex and continent of residence.MethodsIn this retrospective cohort study, we sourced data from the International Mismatch Repair Consortium, which comprises 273 members from 122 research centres or clinics in 32 countries from six continents who are involved in Lynch syndrome research. Families with at least three members and at least one confirmed carrier of a pathogenic or likely pathogenic variant in a DNA mismatch repair gene (MLH1, MSH2, MSH6, or PMS2) were included. The families of probands with known de-novo pathogenic variants were excluded. Data were collected on the method of ascertainment of the family, sex, carrier status, cancer diagnoses, and ages at the time of pedigree collection and at last contact or death. We used a segregation analysis conditioned on ascertainment to estimate the mean penetrance of colorectal cancer and modelled unmeasured polygenic factors to estimate the variation in penetrance. The existence of unknown familial risk factors modifying colorectal cancer risk for Lynch syndrome carriers was tested by use of a Wald p value for the null hypothesis that the polygenic SD is zero.Findings5585 families with Lynch syndrome from 22 countries were eligible for the analysis. Of these, there were insufficient numbers to estimate penetrance for Asia and South America, and for those with EPCAM variants. Therefore, we used data (collected between July 11, 2014, and Dec 31, 2018) from 5255 families (1829 MLH1, 2179 MSH2, 798 MSH6, and 449 PMS2), comprising 79 809 relatives, recruited in 15 countries in North America, Europe, and Australas

Journal article

Ahmad A, Wilson A, Moorghen M, Dhillon AS, Thomas-Gibson S, Suzuki N, Humphries A, Haycock A, Monahan KJ, Vance M, Saunders BPet al., 2021, HIGH CONFIDENCE OPTICAL DIAGNOSIS OF SMALL POLYPS AT COLONOSCOPY VERSUS HISTOPATHOLOGY: MOVING TOWARDS A NEW GOLD STANDARD?, Publisher: MOSBY-ELSEVIER, Pages: AB89-AB89, ISSN: 0016-5107

Conference paper

Ahmad A, Wilson A, Thomas-Gibson S, Suzuki N, Humphries A, Haycock A, Monahan KJ, Vance M, Dhillon AS, Saunders BPet al., 2021, LEARNING CURVE OF OPTICAL DIAGNOSIS WITH A RESECT AND DISCARD STRATEGY FOR SCREENING COLONOSCOPY: PRELIMINARY RESULTS FROM THE DISCARD3 STUDY, Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S138-S138, ISSN: 0016-5085

Conference paper

D'Souza N, Delisle TG, Chen M, Benton SC, Abulafi Met al., 2021, Faecal immunochemical testing in symptomatic patients to prioritize investigation: diagnostic accuracy from NICE FIT Study, BRITISH JOURNAL OF SURGERY, Vol: 108, Pages: 804-810, ISSN: 0007-1323

Journal article

Ahmad A, Wilson A, Thomas-Gibson S, Suzuki N, Humphries A, Haycock A, Monahan K, Vance M, Dhillon A, Saunders Bet al., 2021, Patient Acceptability of Optical Diagnosis for Diminutive Polyps With a Resect And Discard Strategy In Bowel Cancer Screening Colonoscopy, ESGE Days 2021, Publisher: Georg Thieme Verlag KG, ISSN: 1438-8812

Conference paper

Richardson-Thibodeau J, Norton B, Monahan K, 2021, THE DIAGNOSTIC YIELD OF SURVEILLANCE COLONOSCOPY IN POST-COLORECTAL CANCER PATIENTS, Publisher: BMJ PUBLISHING GROUP, Pages: A77-A77, ISSN: 0017-5749

Conference paper

Ahmad A, Dhillon A, Wilson A, Suzuki N, Thomas-Gibson S, Humphries A, Haycock A, Monahan K, Vance M, Saunders Bet al., 2021, EARLY EVALUATION OF A COMPUTER ASSISTED POLYP DETECTION SYSTEM IN BOWEL CANCER SCREENING, Publisher: BMJ PUBLISHING GROUP, Pages: A42-A42, ISSN: 0017-5749

Conference paper

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