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Article ; Online: Evaluating colonoscopy screening intervals in patients with Lynch syndrome from a large Canadian registry.

Aronson, Melyssa / Gryfe, Robert / Choi, Yun-Hee / Semotiuk, Kara / Holter, Spring / Ward, Thomas / Gallinger, Steve / Cohen, Zane / Briollais, Laurent

Journal of the National Cancer Institute

2023 Volume 115, Issue 7, Page(s) 778–787

Abstract: Background: Lynch syndrome (LS) screening guidelines originally recommended colonoscopy every 1 to 2 years, beginning between the ages of 20 and 25 years. Recent studies have questioned the benefits of these short screening intervals in preventing ... ...

Abstract	Background: Lynch syndrome (LS) screening guidelines originally recommended colonoscopy every 1 to 2 years, beginning between the ages of 20 and 25 years. Recent studies have questioned the benefits of these short screening intervals in preventing colorectal cancer (CRC). Our goal is to determine how colonoscopy screening intervals impact CRC in patients with LS. Methods: We analyzed the demographics, screening practices, and outcomes of patients with LS identified through the clinic based Familial Gastrointestinal Cancer Registry at the Zane Cohen Centre, Sinai Health System, Toronto, Canada. Results: A total of 429 patients with LS were identified with median follow-up of 9.2 years; 44 developed CRC. We found a positive trend between shorter screening intervals and the number of adenomas detected during colonoscopy. Any new adenoma detected at screening decreased 10-year CRC incidence by 11.3%. For MLH1 carriers, a screening interval of 1-2 years vs 2-3 years led to a 20-year cumulative CRC risk reduction of 28% and 14% in females and males, respectively. For MSH2 carriers, this risk reduction was 29% and 17%, respectively, and for male MSH6 carriers 18%. Individuals without any adenomas detected (53.4% of LS carriers) had an increased 20-year CRC risk of 25.7% and 57.2% for women and men, respectively, compared with those diagnosed with adenomas at screening. Conclusions: The recommended colonoscopy screening interval of 1-2 years is efficient at detecting adenomas and reducing CRC risk. The observation that 53.4% of LS patients never had an adenoma warrants further investigation about a possible adenoma-free pathway.
MeSH term(s)	Humans ; Male ; Female ; Young Adult ; Adult ; Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis ; Colorectal Neoplasms, Hereditary Nonpolyposis/epidemiology ; Colorectal Neoplasms, Hereditary Nonpolyposis/genetics ; Colorectal Neoplasms/diagnosis ; Colorectal Neoplasms/epidemiology ; Colorectal Neoplasms/prevention & control ; Canada/epidemiology ; Colonoscopy ; Adenoma/diagnosis ; Adenoma/epidemiology ; Adenoma/prevention & control ; Registries
Language	English
Publishing date	2023-02-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2992-0
ISSN	1460-2105 ; 0027-8874 ; 0198-0157
ISSN (online)	1460-2105
ISSN	0027-8874 ; 0198-0157
DOI	10.1093/jnci/djad058
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Article: Digital quantitative tissue image analysis of hypoxia in resected pancreatic ductal adenocarcinomas.

Siddiqui, Iram / Bilkey, Jade / McKee, Trevor D / Serra, Stefano / Pintilie, Melania / Do, Trevor / Xu, Jing / Tsao, Ming-Sound / Gallinger, Steve / Hill, Richard P / Hedley, David W / Dhani, Neesha C

Frontiers in oncology

2022 Volume 12, Page(s) 926497

Abstract: Background: Tumor hypoxia is theorized to contribute to the aggressive biology of pancreatic ductal adenocarcinoma (PDAC). We previously reported that hypoxia correlated with rapid tumor growth and metastasis in patient-derived xenografts. Anticipating ... ...

Abstract	Background: Tumor hypoxia is theorized to contribute to the aggressive biology of pancreatic ductal adenocarcinoma (PDAC). We previously reported that hypoxia correlated with rapid tumor growth and metastasis in patient-derived xenografts. Anticipating a prognostic relevance of hypoxia in patient tumors, we developed protocols for automated semi-quantitative image analysis to provide an objective, observer-independent measure of hypoxia. We further validated this method which can reproducibly estimate pimonidazole-detectable hypoxia in a high-through put manner. Methods: We studied the performance of three automated image analysis platforms in scoring pimonidazole-detectable hypoxia in resected PDAC (n = 10) in a cohort of patients enrolled in PIMO-PANC. Multiple stained tumor sections were analyzed on three independent image-analysis platforms, Aperio Genie (AG), Definiens Tissue Studio (TS), and Definiens Developer (DD), which comprised of a customized rule set. Results: The output from Aperio Genie (AG) had good concordance with manual scoring, but the workflow was resource-intensive and not suited for high-throughput analysis. TS analysis had high levels of variability related to misclassification of cells class, while the customized rule set of DD had a high level of reliability with an intraclass coefficient of more than 85%. Discussion: This work demonstrates the feasibility of developing a robust, high-performance pipeline for an automated, quantitative scoring of pimonidazole-detectable hypoxia in patient tumors.
Language	English
Publishing date	2022-08-01
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2022.926497
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Article ; Online: Long-term outcomes of laparoscopic liver resection for hepatocellular carcinoma: A propensity score matched analysis of a high-volume North American center.

Ivanics, Tommy / Claasen, Marco Paw / Patel, Madhukar S / Rajendran, Luckshi / Shwaartz, Chaya / Raschzok, Nathanael / Yoon, Peter / Murillo Perez, Carla F / Hansen, Bettina E / Muaddi, Hala / Moulton, Carol-Anne / Reichman, Trevor / Ghanekar, Anand / Gallinger, Steve / McGilvray, Ian / Cleary, Sean P / Sapisochin, Gonzalo

Surgery

2021 Volume 171, Issue 4, Page(s) 982–991

Abstract: Background: Laparoscopic liver resections for malignancy are increasing worldwide, and yet data from North America are lacking. We aimed to assess the long-term outcomes of patients undergoing laparoscopic liver resection and open liver resection as a ... ...

Abstract	Background: Laparoscopic liver resections for malignancy are increasing worldwide, and yet data from North America are lacking. We aimed to assess the long-term outcomes of patients undergoing laparoscopic liver resection and open liver resection as a treatment for hepatocellular carcinoma. Methods: Patients undergoing liver resection for hepatocellular carcinoma between January 2008 and December 2019 were retrospectively studied. A propensity score matching was performed using patient demographics, laboratory parameters, etiology of liver disease, liver function, and tumor characteristics. Primary outcomes included overall survival and cumulative incidence of recurrence. Kaplan-Meier and competing risk cumulative incidence were used for survival analyses. Multivariable Cox regression and Fine-Gray proportional hazard regression were performed to determine hazard for death and recurrence, respectively. Results: Three hundred and ninety-one patients were identified (laparoscopic liver resection: 110; open liver resection: 281). After propensity score matching, 149 patients remained (laparoscopic liver resection: 57; open liver resection: 92). There were no significant differences between groups with regard to extent of hepatectomy performed and tumor characteristics. The laparoscopic liver resection group experienced a lower proportion of ≥Clavien-Dindo grade III complications (14% vs 29%; P = .01). In the matched cohort, the 1-, 3-, and 5-year overall survival rate in the laparoscopic liver resection versus open liver resection group was 90.9%, 79.3%, 70.5% vs 91.3%, 88.5%, 83.1% (P = .26), and the cumulative incidence of recurrence 31.1%, 59.7%, 62.9% vs 18.9%, 40.6%, 49.2% (P = .06), respectively. Conclusion: This study represents the largest single institutional study from North America comparing long-term oncologic outcomes of laparoscopic liver resection and open liver resection as a treatment for primary hepatocellular carcinoma. The combination of reduced short-term complications and equivalent long-term oncologic outcomes favor the laparoscopic approach when feasible.
MeSH term(s)	Carcinoma, Hepatocellular ; Disease-Free Survival ; Hepatectomy/adverse effects ; Humans ; Laparoscopy/adverse effects ; Length of Stay ; Liver Neoplasms ; Propensity Score ; Retrospective Studies ; Treatment Outcome
Language	English
Publishing date	2021-11-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	202467-6
ISSN	1532-7361 ; 0039-6060
ISSN (online)	1532-7361
ISSN	0039-6060
DOI	10.1016/j.surg.2021.10.017
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Article ; Online: GATA4 and GATA6 loss-of-expression is associated with extinction of the classical programme and poor outcome in pancreatic ductal adenocarcinoma.

de Andrés, Mónica P / Jackson, Richard J / Felipe, Irene / Zagorac, Sladjana / Pilarsky, Christian / Schlitter, Anna Melissa / Martinez de Villareal, Jaime / Jang, Gun Ho / Costello, Eithne / Gallinger, Steve / Ghaneh, Paula / Greenhalf, William / Knösel, Thomas / Palmer, Daniel H / Ruemmele, Petra / Weichert, Wilko / Buechler, Markus / Hackert, Thilo / Neoptolemos, John P /

Notta, Faiyaz / Malats, Núria / Martinelli, Paola / Real, Francisco X

Gut

2022 Volume 72, Issue 3, Page(s) 535–548

Abstract: Objective: GATA6 is a key regulator of the classical phenotype in pancreatic ductal adenocarcinoma (PDAC). Low GATA6 expression associates with poor patient outcome. : Design: We analysed PDAC transcriptomic data, stratifying cases according to : ... ...

Abstract	Objective: GATA6 is a key regulator of the classical phenotype in pancreatic ductal adenocarcinoma (PDAC). Low GATA6 expression associates with poor patient outcome. Design: We analysed PDAC transcriptomic data, stratifying cases according to Results: GATA4 Conclusions: GATA4
MeSH term(s)	Humans ; Pancreatic Neoplasms/pathology ; Pancreas/pathology ; Carcinoma, Pancreatic Ductal/pathology ; Gene Expression Profiling ; GATA6 Transcription Factor/genetics ; GATA4 Transcription Factor/genetics ; GATA4 Transcription Factor/metabolism
Chemical Substances	GATA6 Transcription Factor ; GATA4 Transcription Factor ; GATA4 protein, human ; GATA6 protein, human
Language	English
Publishing date	2022-09-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80128-8
ISSN	1468-3288 ; 0017-5749
ISSN (online)	1468-3288
ISSN	0017-5749
DOI	10.1136/gutjnl-2021-325803
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Article ; Online: Management and surveillance of non-functional pancreatic neuroendocrine tumours: Retrospective review.

Yohanathan, Lavanya / Dossa, Fahima / St Germain, Amelie Tremblay / Golbafian, Faegheh / Moulton, Carol-Anne / McGilvray, Ian D / Greig, Paul D / Serra, Stefano / Wei, Alice C / Jhaveri, Kartik S / Gallinger, Steve / Cleary, Sean P

Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.

2019 Volume 19, Issue 2, Page(s) 360–366

Abstract: Background: /Objective. To determine the outcomes of a non-operative management approach for sporadic, small, non-functional pancreatic neuroendocrine tumours.: Methods: A retrospective chart review of patients with non-functional pancreatic ... ...

Abstract	Background: /Objective. To determine the outcomes of a non-operative management approach for sporadic, small, non-functional pancreatic neuroendocrine tumours. Methods: A retrospective chart review of patients with non-functional pancreatic neuroendocrine tumours initially managed non-operatively at a single institution was performed. Patients were identified through a search of radiologic reports, and individuals with ≥2 cross-sectional imaging studies performed >6 months apart from Jan. 1, 2000 to Dec. 31, 2013 were included. Data on tumour size, radiologic characteristics at diagnosis, interval radiologic growth, and surgical outcomes were recorded. Results: Over the thirteen-year study period, 95 patients met inclusion criteria and were followed radiologically for a median of 36 months (18-69 months). Median initial tumour size on first imaging was 14.0 mm (IQR 10-19 mm). Median overall tumour growth rate was 0.03 mm/month (IQR: 0.00-0.14 mm/month). There was no significant relationship between initial tumour size and growth rate for tumours ≤ 2 cm or for lesions between 2 and 4 cm. Thirteen (14%) patients initially managed non-operatively underwent resection during the follow-up period. Reasons for surgery included interval tumour growth, patient anxiety or preference, or diagnostic uncertainty. Median time to surgery was 14 months (IQR 8-19 months). No patients progressed beyond resectability or developed metastatic disease during the observation period. Conclusion: For patients with sporadic, small, non-functional pancreatic neuroendocrine tumours, radiologic surveillance appears to be a safe initial approach to management.
MeSH term(s)	Aged ; Female ; Humans ; Male ; Middle Aged ; Neuroendocrine Tumors/pathology ; Neuroendocrine Tumors/therapy ; Pancreatic Neoplasms/pathology ; Pancreatic Neoplasms/therapy ; Retrospective Studies
Language	English
Publishing date	2019-02-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2056680-3
ISSN	1424-3911 ; 1424-3903
ISSN (online)	1424-3911
ISSN	1424-3903
DOI	10.1016/j.pan.2019.02.008
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Article ; Online: Evaluating the utility of tumour mutational signatures for identifying hereditary colorectal cancer and polyposis syndrome carriers.

Gut

2021 Volume 70, Issue 11, Page(s) 2138–2149

Abstract: Objective: Germline pathogenic variants (PVs) in the DNA mismatch repair (MMR) genes and in the base excision repair gene : Design: Whole-exome sequencing of formalin-fixed paraffin-embedded (FFPE) CRC tissue was performed on 33 MMR germline PV ... ...

Abstract	Objective: Germline pathogenic variants (PVs) in the DNA mismatch repair (MMR) genes and in the base excision repair gene Design: Whole-exome sequencing of formalin-fixed paraffin-embedded (FFPE) CRC tissue was performed on 33 MMR germline PV carriers, 12 biallelic Results: The combination of mutational signatures SBS18 and SBS36 contributing >30% of a CRC's signature profile was able to discriminate biallelic Conclusion: Assessment of SBS and ID signatures can discriminate CRCs from biallelic
MeSH term(s)	Adenomatous Polyposis Coli/genetics ; Colorectal Neoplasms/genetics ; DNA Glycosylases ; DNA Mismatch Repair ; Female ; Genetic Predisposition to Disease ; Germ-Line Mutation ; Heterozygote ; Humans ; Male ; Middle Aged ; MutL Protein Homolog 1 ; Syndrome ; Whole Exome Sequencing
Chemical Substances	MLH1 protein, human ; DNA Glycosylases (EC 3.2.2.-) ; mutY adenine glycosylase (EC 3.2.2.-) ; MutL Protein Homolog 1 (EC 3.6.1.3)
Language	English
Publishing date	2021-01-07
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80128-8
ISSN	1468-3288 ; 0017-5749
ISSN (online)	1468-3288
ISSN	0017-5749
DOI	10.1136/gutjnl-2019-320462
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Article ; Online: Endoscopic or percutaneous biliary drainage for Klatskin tumors?

Walter, Thomas / Ho, Chia S / Horgan, Anne M / Warkentin, Andrew / Gallinger, Steve / Greig, Paul D / Kortan, Paul / Knox, Jennifer J

Journal of vascular and interventional radiology : JVIR

2013 Volume 24, Issue 1, Page(s) 113–121

Abstract: Purpose: Controversy exists regarding the preferred biliary drainage technique in patients with Klatskin tumors because few comparative studies exist. This study compared outcomes of endoscopic biliary drainage (EBD) and percutaneous transhepatic ... ...

Abstract	Purpose: Controversy exists regarding the preferred biliary drainage technique in patients with Klatskin tumors because few comparative studies exist. This study compared outcomes of endoscopic biliary drainage (EBD) and percutaneous transhepatic biliary drainage (PTBD). Materials and methods: Consecutive patients (N = 129) with Klatskin tumors treated with initial EBD or PTBD were identified, and their clinical histories were retrospectively reviewed. The primary endpoint was the time to therapeutic success (TTS), defined as the time between the first drainage and a total bilirubin measurement of 40 μmol/L or lower. Results: EBD was the first biliary decompression procedure performed in 87 patients; PTBD was performed first in 42. Technical success rates (78% with EBD vs 98% with PTBD; P = .004) and therapeutic success rates (49% vs 79%, respectively; P = .002) were significantly lower in the EBD group than in the PTBD group. Forty-four patients in the EBD group (51%) subsequently underwent PTBD before therapeutic success was achieved or antitumoral treatment was started. Median TTSs were 61 days in the EBD group and 44 days in the PTBD group, and multivariate analysis showed a hazard ratio of 0.63 (95% confidence interval, 0.41-0.99; P = .045). In patients treated with surgery or chemotherapy with or without radiation therapy, median times to treatment were 76 and 68 days in the EBD and PTBD groups, respectively (P = .76). Cholangitis occurred in 25% and 21% of patients in the EBD and PTBD groups, respectively (P = .34). Conclusions: PTBD should be seriously considered for biliary decompression when treating patients with Klatskin tumor.
MeSH term(s)	Aged ; Aged, 80 and over ; Bile Duct Neoplasms/mortality ; Bile Duct Neoplasms/surgery ; Drainage/mortality ; Endoscopy, Digestive System/mortality ; Female ; Hepatic Duct, Common/surgery ; Humans ; Klatskin Tumor/mortality ; Klatskin Tumor/surgery ; Male ; Middle Aged ; Ontario/epidemiology ; Postoperative Complications/mortality ; Prevalence ; Retrospective Studies ; Risk Factors ; Survival Analysis ; Survival Rate ; Treatment Outcome
Language	English
Publishing date	2013-01
Publishing country	United States
Document type	Journal Article ; Multicenter Study
ZDB-ID	1137756-2
ISSN	1535-7732 ; 1051-0443
ISSN (online)	1535-7732
ISSN	1051-0443
DOI	10.1016/j.jvir.2012.09.019
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Article ; Online: Practice patterns for the management of hepatic metastases from colorectal cancer: a mixed methods analysis.

Wei, Alice C / Sandhu, Lakhbir / Devitt, Katharine S / Gagliardi, Anna R / Kennedy, Erin D / Urbach, David R / Gallinger, Steve / Baxter, Nancy N

Annals of surgical oncology

2013 Volume 20, Issue 5, Page(s) 1567–1574

Abstract: Purpose: The optimal management of colorectal cancer liver metastases (CRC-LM) has changed during the past two decades. However, clinical practice lags behind best evidence recommendations. We sought to characterize the gap between current practice and ... ...

Abstract	Purpose: The optimal management of colorectal cancer liver metastases (CRC-LM) has changed during the past two decades. However, clinical practice lags behind best evidence recommendations. We sought to characterize the gap between current practice and best evidence for the management of these patients and to identify barriers that hamper effective utilization of metastasectomy. Methods: A mixed-methods approach was used. A survey was mailed to all general surgeons (GS) and medical oncologists (MO) in Ontario, Canada. Domains examined included: physician/practice characteristics, indications for hepatectomy, use of multi-modality therapy and referral patterns. Physician focus groups were conducted that explored issues relating to access to care. Results: The survey was mailed to 942 physicians with a response rate of 68 % (n = 348; GS n = 295, 69 %; MO n = 53, 63 %). Current practice patterns demonstrated that 97 % of physicians refer patients with low tumor burden (e.g., solitary CRC-LM), but referral rates for hepatectomy decreased as the tumor burden increased. Physicians still consider extrahepatic disease as a strong contraindication to metastasectomy. Barriers to care included: economic, time, and resource constraints; lack of physician engagement, local medical expertise, and high-quality guidelines. Multidisciplinary cancer conferences were identified as an enabler of clinical care and a potential platform for the acquisition of new medical knowledge. Conclusions: Current management of CRC-LM does not reflect best evidence. Patients who may benefit from surgery are not being referred for metastasectomy. We have identified an evidence-practice gap at the level of physician, which should be targeted with novel quality improvement strategies.
MeSH term(s)	Clinical Competence ; Colorectal Neoplasms/pathology ; Combined Modality Therapy ; Contraindications ; Evidence-Based Medicine ; Female ; Focus Groups ; General Surgery/statistics & numerical data ; Hepatectomy ; Humans ; Liver Neoplasms/secondary ; Liver Neoplasms/therapy ; Logistic Models ; Male ; Medical Oncology/statistics & numerical data ; Multivariate Analysis ; Neoplasm Staging ; Ontario ; Practice Patterns, Physicians'/economics ; Practice Patterns, Physicians'/statistics & numerical data ; Referral and Consultation/statistics & numerical data ; Surveys and Questionnaires ; Urban Health Services/statistics & numerical data
Language	English
Publishing date	2013-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1200469-8
ISSN	1534-4681 ; 1068-9265
ISSN (online)	1534-4681
ISSN	1068-9265
DOI	10.1245/s10434-012-2698-3
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Article ; Online: A genome-wide search for determinants of survival in 1926 patients with advanced colorectal cancer with follow-up in over 22,000 patients.

Wills, Christopher / He, Yazhou / Summers, Matthew G / Lin, Yi / Phipps, Amanda I / Watts, Katie / Law, Philip J / Al-Tassan, Nada A / Maughan, Timothy S / Kaplan, Richard / Houlston, Richard S / Peters, Ulrike / Newcomb, Polly A / Chan, Andrew T / Buchanan, Daniel D / Gallinger, Steve / Marchand, Loic L / Pai, Rish K / Shi, Qian /

Alberts, Steven R / Gray, Victoria / West, Hannah D / Escott-Price, Valentina / Dunlop, Malcolm G / Cheadle, Jeremy P

European journal of cancer (Oxford, England : 1990)

2021 Volume 159, Page(s) 247–258

Abstract: Background: While genome-wide association studies (GWAS) have identified germline variants influencing the risk of developing colorectal cancer (CRC), there has been limited examination of the possible role of inherited variation as a determinant of ... ...

Abstract	Background: While genome-wide association studies (GWAS) have identified germline variants influencing the risk of developing colorectal cancer (CRC), there has been limited examination of the possible role of inherited variation as a determinant of patient outcome. Patients and methods: We performed a GWAS for overall survival (OS) in 1926 patients with advanced CRC from the COIN and COIN-B clinical trials. For single nucleotide polymorphisms (SNPs) showing an association with OS (P < 1.0 × 10 Results: The most significant SNP associated with OS was rs79612564 in ERBB4 (hazard ratio [HR] = 1.24, 95% confidence interval [CI] = 1.16-1.32, P = 1.9 × 10 Conclusions: Genetic and expression data support a potential role for rs79612564 in the receptor tyrosine kinase ERBB4 as a predictive biomarker of survival.
MeSH term(s)	Adenocarcinoma/genetics ; Adenocarcinoma/mortality ; Biomarkers, Tumor/genetics ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/mortality ; Genome-Wide Association Study ; Genotype ; Humans ; Polymorphism, Single Nucleotide ; Receptor, ErbB-4/genetics
Chemical Substances	Biomarkers, Tumor ; ERBB4 protein, human (EC 2.7.10.1) ; Receptor, ErbB-4 (EC 2.7.10.1)
Language	English
Publishing date	2021-11-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	82061-1
ISSN	1879-0852 ; 0277-5379 ; 0959-8049 ; 0964-1947
ISSN (online)	1879-0852
ISSN	0277-5379 ; 0959-8049 ; 0964-1947
DOI	10.1016/j.ejca.2021.09.047
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Article ; Online: Genetic testing for Lynch syndrome in the province of Ontario.

Wang, Marina / Aldubayan, Saud / Connor, Ashton A / Wong, Beatrix / Mcnamara, Kate / Khan, Tahsin / Semotiuk, Kara / Khalouei, Sam / Holter, Spring / Aronson, Melyssa / Cohen, Zane / Gallinger, Steve / Charames, George / Pollett, Aaron / Lerner-Ellis, Jordan

Cancer

2016 Volume 122, Issue 11, Page(s) 1672–1679

Abstract: Background: In November 2001, genetic testing for Lynch syndrome (LS) was introduced by the Ministry of Health and Long-Term Care (MOH) in Ontario for individuals at high risk for LS cancers according to either tumor immunohistochemistry staining or ... ...

Abstract	Background: In November 2001, genetic testing for Lynch syndrome (LS) was introduced by the Ministry of Health and Long-Term Care (MOH) in Ontario for individuals at high risk for LS cancers according to either tumor immunohistochemistry staining or their family history. This article describes the outcomes of the program and makes recommendations for improving it and informing other public health care programs. Methods: Subjects were referred for molecular testing of the mismatch repair (MMR) genes MutL homolog 1, MutS homolog 2, and MutS homolog 6 if they met 1 of 7 MOH criteria. Testing was conducted from January 2001 to March 2015 at the Molecular Diagnostic Laboratory of Mount Sinai Hospital in Toronto. Results: A total of 1452 subjects were tested. Of the 662 subjects referred for testing because their tumor was immunodeficient for 1 or more of the MMR genes, 251 (37.9%) carried a germline mutation. In addition, 597 subjects were tested for a known family mutation, and 298 (49.9%) were positive; 189 of these 298 subjects (63.4%) were affected with cancer at the time of testing. An additional 193 subjects were referred because of a family history of LS, and 34 of these (17.6%) had a mutation identified. Conclusions: These results indicate that the provincial criteria are useful in identifying LS carriers after an MMR-deficient tumor is identified. Placing greater emphasis on testing unaffected relatives in families with a known mutation may identify more unaffected carriers and facilitate primary prevention in those individuals. Cancer 2016;122:1672-9. © 2016 American Cancer Society.
MeSH term(s)	Adolescent ; Adult ; Aged ; Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis ; Colorectal Neoplasms, Hereditary Nonpolyposis/genetics ; DNA Mismatch Repair ; DNA-Binding Proteins/genetics ; Family Health ; Female ; Genetic Testing/methods ; Germ-Line Mutation ; Heterozygote ; Humans ; Male ; Microsatellite Instability ; Middle Aged ; MutL Protein Homolog 1/genetics ; MutS Homolog 2 Protein/genetics ; Ontario ; Program Evaluation ; Young Adult
Chemical Substances	DNA-Binding Proteins ; G-T mismatch-binding protein ; MLH1 protein, human ; MutL Protein Homolog 1 (EC 3.6.1.3) ; MutS Homolog 2 Protein (EC 3.6.1.3)
Language	English
Publishing date	2016--01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1429-1
ISSN	1097-0142 ; 0008-543X ; 1934-662X
ISSN (online)	1097-0142
ISSN	0008-543X ; 1934-662X
DOI	10.1002/cncr.29950
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Uh III Zs.146: Show issues

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