Search Our Scientific Publications & Authors

JAMA Oncol 2020 Jul 2. Epub 2020 Jul 2.

Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.

Importance: The limited data on cancer phenotypes in men with germline BRCA1 and BRCA2 pathogenic variants (PVs) have hampered the development of evidence-based recommendations for early cancer detection and risk reduction in this population.

Objective: To compare the cancer spectrum and frequencies between male BRCA1 and BRCA2 PV carriers.

Design, Setting, And Participants: Retrospective cohort study of 6902 men, including 3651 BRCA1 and 3251 BRCA2 PV carriers, older than 18 years recruited from cancer genetics clinics from 1966 to 2017 by 53 study groups in 33 countries worldwide collaborating through the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Read More

BMJ Case Rep 2020 Jul 1;13(7). Epub 2020 Jul 1.

Pediatrics, Ohio State University College of Medicine, Columbus, Ohio, USA

The diagnosis of paediatric colorectal cancer is an unusual finding often diagnosed at an advanced stage with associated poor survival. Paediatric colorectal cancer warrants investigation for hereditary cancer predisposition syndromes, including Lynch syndrome. Here we describe a 16-year-old girl who presented with a stage IIA mucinous adenocarcinoma of the descending colon (T3 N0 M0) treated by resection alone that was associated with a pathogenic germline mutation of (c. Read More

J Clin Med 2020 Jun 23;9(6). Epub 2020 Jun 23.

Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL, Hospitalet de Llobregat, 08908 Barcelona, Spain.

In the past two decades, multiple studies have been undertaken to elucidate the genetic cause of the predisposition to mismatch repair (MMR)-proficient nonpolyposis colorectal cancer (CRC). Here, we present the proposed candidate genes according to their involvement in specific pathways considered relevant in hereditary CRC and/or colorectal carcinogenesis. To date, only pathogenic variants in may be convincedly linked to hereditary CRC. Read More

JAMA Netw Open 2020 Jun 1;3(6):e208958. Epub 2020 Jun 1.

Division of Gastroenterology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.

Importance: There are insufficient data describing the incidence and risk factors of postcolonoscopy complications in older individuals.

Objective: To assess the association between older age (≥75 years) and the risk of postcolonoscopy complications.

Design, Setting, And Participants: This population-based retrospective cohort study included adults (≥50 years) undergoing outpatient colonoscopy between April 2008 and September 2017, identified from Ontario administrative databases. Read More

Biomedicines 2020 Jun 19;8(6). Epub 2020 Jun 19.

Department of Molecular Medicine and Medical Biotechnology, University Federico II, via Pansini 5, 80131 Naples, Italy.

Background: The loss or low expression of DNA mismatch repair (MMR) genes can result in genomic instability and tumorigenesis. One such gene, MSH2, is mutated or rearranged in Lynch syndrome (LS), which is characterized by a high risk of tumor development, including colorectal cancer. However, many variants identified in this gene are often defined as variants of uncertain significance (VUS). Read More

BMJ Open 2020 Jun 21;10(6):e036475. Epub 2020 Jun 21.

Cancer Research Division, Cancer Council NSW, Woolloomooloo, New South Wales, Australia.

Introduction: With almost 50% of cases preventable and the Australian National Bowel Cancer Screening Program in place, colorectal cancer (CRC) is a prime candidate for investment to reduce the cancer burden. The challenge is determining effective ways to reduce morbidity and mortality and their implementation through policy and practice. -Bowel is a multistage programme that aims to identify best-value investment in CRC control by integrating expert and end-user engagement; relevant evidence; modelled interventions to guide future investment; and policy-driven implementation of interventions using evidence-based methods. Read More

Jpn J Clin Oncol 2020 Jun 17. Epub 2020 Jun 17.

Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Kawagoe.

Polymerase proofreading-associated polyposis, caused by germline variants in the exonuclease domains of POLD1 and POLE, is a dominantly inherited rare condition characterized by oligo-adenomatous polyposis and increased risk of colorectal cancer, endometrial cancer and brain tumours. We report the first Japanese case of polymerase proofreading-associated polyposis carrying a POLD1 variant. The proband was a Japanese woman who had undergone resections of early colorectal carcinomas repeatedly and a hysterectomy with bilateral oophorectomy for endometrial cancer, all of which were diagnosed within 2 years after the first colectomy at 49 year old. Read More

BMJ Open 2020 Jun 15;10(6):e033552. Epub 2020 Jun 15.

Cancer Council New South Wales, Woolloomooloo, New South Wales, Australia.

Introduction: In multisite intervention trials, implementation success often varies widely across settings. Process evaluations are crucial to interpreting trial outcomes and understanding contextual factors and causal chains necessary for successful implementation. Lynch syndrome is a hereditary cancer predisposition conferring an increased risk of colorectal, endometrial and other cancer types. Read More

Lancet 2020 06;395(10240):1855-1863

Division of Haematology and Immunology, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK.

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. Read More

Lancet 2020 06;395(10240):1817-1818

Harvard Medical School, Boston, MA, USA; Massachusetts General Hospital, Boston, MA 02114, USA. Electronic address:

Clin Gastroenterol Hepatol 2020 Jun 7. Epub 2020 Jun 7.

Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona.

Though sporadic colorectal cancer (CRC) has historically been a disease that affected people later in life, the incidence of CRC is increasing in people less than 50 years of age. Approximately 20% of young adult onset CRC cases are caused by known hereditary CRC syndromes, but the reasons for this rise in CRC incidence in younger people who do not have a recognized familial condition are not yet known. It is imperative that primary care physicians and gastroenterologists offer appropriate screening for individuals at risk for hereditary CRC and offer prompt diagnostic evaluation for all patients presenting with signs and symptoms suggestive of CRC, regardless of their age. Read More

J Transl Med 2020 Jun 10;18(1):232. Epub 2020 Jun 10.

Cancer Genetics Group, Institute of Genetics and Molecular Biology (UVa-CSIC), Sanz y Forés 3, 47003, Valladolid, Spain.

Background: In the context of our Regional Program of Hereditary Cancer, individuals fulfilling the criteria are tested for germline mutations to subsequently establish the clinical management. Our standard diagnostic approach focuses on sequencing a few classic high-risk genes, a method that frequently renders uninformative genetic results. This study aims to examine the improved yield offered by an On-Demand panel. Read More

Pathogens 2020 Jun 8;9(6). Epub 2020 Jun 8.

College of Medicine, QU Health, Qatar University, 2713 Doha, Qatar.

Colorectal cancer (CRC) is a common malignancy with a high mortality rate worldwide. It is a complex, multifactorial disease that is strongly impacted by both hereditary and environmental factors. The role of microbes (e. Read More

J Clin Med 2020 Jun 4;9(6). Epub 2020 Jun 4.

Department of Applied Tumor Biology, Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany.

Microsatellite instability (MSI) represents one of the major types of genomic instability in human cancers and is most common in colorectal cancer (CRC) and endometrial cancer (EC). MSI develops as a consequence of DNA mismatch repair (MMR) deficiency, which can occur sporadically or in the context of Lynch syndrome (LS), the most common inherited tumor syndrome. MMR deficiency triggers the accumulation of high numbers of somatic mutations in the affected cells, mostly indel mutations at microsatellite sequences. Read More

Eur J Cancer Care (Engl) 2020 Jun 8:e13276. Epub 2020 Jun 8.

Section of Hygiene, Department of Biomedical Sciences, Università Politecnica delle Marche, Ancona, Italy.

Objective: International guidelines recommend genetic counselling and if indicated the genetic testing for treatment, disease prevention and follow-up for patients and their relatives. However, there is limited utilisation of genetic counselling. This study aimed to verify whether an individual semi-structured guideline-based interview improves the identification of patients eligible for genetic counselling. Read More

Int J Cancer 2020 Jun 8. Epub 2020 Jun 8.

Department of Human Genetics, Radboud university medical center, Nijmegen, The Netherlands.

Universal mismatch repair deficiency (dMMR) testing of colorectal cancer (CRC) is promoted as routine diagnostics to prescreen for Lynch syndrome. We evaluated the yield and experience of age-related molecular investigation for heritable and nonheritable causes of dMMR in CRC below age 70 to identify Lynch Syndrome. In a prospective cohort of 3602 newly diagnosed CRCs below age 70 from 19 hospitals, dMMR, MLH1 promoter hypermethylation, germline MMR gene and somatic MMR gene testing was assessed in daily practice. Read More

Fam Cancer 2020 Jun 8. Epub 2020 Jun 8.

Department of Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic, Cleveland, OH, USA.

Familial adenomatous polyposis (FAP) is a hereditary colorectal cancer syndrome characterized by colorectal adenomas and a near 100% lifetime risk of colorectal cancer (CRC). Prophylactic colectomy, usually by age 40, is the gold-standard therapy to mitigate this risk. However, colectomy is associated with morbidity and fails to prevent extra-colonic disease manifestations, including gastric polyposis, duodenal polyposis and cancer, thyroid cancer, and desmoid disease. Read More

Fam Cancer 2020 Jun 8. Epub 2020 Jun 8.

Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.

The Prospective Lynch Syndrome Database (PLSD) has been developed as an international, multicentre, prospective, observational study that aims to provide age and organ-specific cancer risks according to gene and gender, estimates of survival after cancer and information on the effects of interventions. Recent reports from PLSD provided improved estimates of cancer risks and survival and showed that different time intervals between surveillance colonoscopies did not affect the incidence, stage or prognosis of colorectal cancer. The PLSD reports suggest that current management guidelines for Lynch syndrome should be revised in light of the different gene and gender-specific cancer risks and the good prognosis for the most commonly associated cancers. Read More

Dig Dis Sci 2020 Jun 4. Epub 2020 Jun 4.

University of Colorado Anschutz Medical Center, 12631 E 17th Avenue, Room 7614, Campus Box 158, 80045, Aurora, CO, USA.

Background: Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome, yet is grossly under-recognized. Multiple professional societies recommend screening all CRCs for LS by performing tumor testing. The veterans affairs system has not adopted universal tumor testing as a national performance metric and leaves screening for LS to clinical care at individual sites. Read More

Clin Gastroenterol Hepatol 2020 May 31. Epub 2020 May 31.

Department of Gastroenterology, Hepatology, and Nutrition, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, United States. Sanford R. Weiss, MD Center for Hereditary Colorectal Neoplasia, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, United States.

Background & Aims: Ampullary and duodenal cancer are the leading causes of death in patients with familial adenomatous polyposis (FAP) after colectomy has been performed. Risk of duodenal cancer is determined based on Spigelman stage (SS) of duodenal polyposis. Guidelines recommend endoscopic surveillance of the duodenum and visualization of the papilla to stage duodenal polyposis. Read More

Ann Gastroenterol Surg 2020 May 27;4(3):229-233. Epub 2020 Mar 27.

Department of Gastroenterological Surgery Graduate School of Medicine Osaka University Osaka Japan.

The incidence of pancreatic cancer is high among those in their sixties to seventies but low in those in their fifties or younger. Although there is no unified definition regarding the age of early-onset pancreatic cancer, previously published reports suggest that, compared to later-onset pancreatic cancer patients, early-onset pancreatic cancer patients tend to be detected at advanced stages and thus have poor prognoses, but they do not show significantly higher rates of patients with genetic factors. On the other hand, it has been reported that patients with familial pancreatic cancer and hereditary pancreatic cancer syndromes often develop pancreatic cancer at a young age. Read More

Curr Oncol 2020 Apr 1;27(2):e182-e190. Epub 2020 May 1.

Sinai Health System, Department of Surgery, University of Toronto, Toronto, ON.

Background: pathogenic variants (pvs) cause most cases of inherited diffuse gastric cancer (dgc), but have low detection rates and vary geographically. In the present study, we examined hereditary causes of dgc in patients in Ontario.

Methods: testing through single-site or multi-gene panels was conducted for patients with dgc meeting the 2015 International Gastric Cancer Linkage Consortium (igclc) criteria, or with isolated dgc at less than 50 years of age, or with a strong family history of cancer identified at the Zane Cohen Centre (zcc). Read More

BMC Gastroenterol 2020 Jun 1;20(1):167. Epub 2020 Jun 1.

Department of Colorectal Surgery, Changhai Hospital, 168 Changhai Road, Shanghai, 200433, China.

Background: Juvenile polyposis syndrome (JPS) is a rare disorder characterized by the presence of multiple juvenile polyps in the gastrointestinal tract, and germline mutations in SMAD4 or BMPR1A. Due to its rarity and complex clinical manifestation, misdiagnosis often occurs in clinical practice.

Case Presentation: A 42-year-old man with multiple pedunculated colorectal polyps and concomitant rectal adenocarcinoma was admitted to our hospital. Read More

Medicine (Baltimore) 2020 May;99(21):e20238

Department of Medical Oncology, the Second Affiliated Hospital, Zhejiang University School of Medicine.

Objects: The present study aimed to identify the clinicopathological characteristics of colorectal cancer (CRC) with invasive micropapillary components (IMPCs) and the relationship between different amounts of micropapillary components and lymph node metastasis.

Methods: A cohort of 363 patients with CRC who underwent surgical treatment in the Second Affiliated Hospital of Zhejiang University School of Medicine between January 2013 and December 2016 were retrospectively reviewed. We compared the clinicopathological characteristics, including survival outcomes and immunohistochemical profiles (EMA, MUC1, MLH1, MSH2, MSH6, and PMS2), between CRC with IMPCs and those with conventional adenocarcinoma (named non-IMPCs in this study). Read More

J Cancer Res Ther Oncol 2020 17;8(1). Epub 2020 Jan 17.

Department of Obstetrics and Gynecology, David Geffen School of Medicine, the University of California at Los Angeles, Los Angeles, CA 90095, USA.

A growing body of literature supports the role of apolipoproteins present in HDL in the treatment of pro-inflammatory diseases including cancer. We examined whether bovine HDL (bHDL) and three dual-domain peptides, namely AEM-28 and its analog AEM-28-2, and HM-10/10, affect tumor growth and development in mouse models of ovarian and colon cancer. We demonstrate that bHDL inhibits mouse colorectal cancer cell line CT26-mediated lung tumor development, and mouse ovarian cancer cell line ID8-mediated tumor burden. Read More

Clin Gastroenterol Hepatol 2020 May 23. Epub 2020 May 23.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden; Division of Digestive and Liver Disease, Department of Medicine, Columbia University Medical Center, New York, New York, USA; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, UK. Electronic address:

Background & Aims: Use of antibiotics affects the composition of the microbiome and might affect development of colorectal polyps, which are precursors to colorectal cancer.

Methods: We performed a nested case-control study in Sweden of 45,744 patients with a colorectal polyp (cases) in the nationwide gastrointestinal ESPRESSO histopathology cohort, using unaffected full siblings as controls (n=93,307). Polyps were classified by morphology SnoMed codes into conventional adenomas and serrated polyps. Read More

Hum Mutat 2020 May 25. Epub 2020 May 25.

Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL, Hospitalet de Llobregat, Barcelona, Spain.

Genome-wide approaches applied for the identification of new hereditary colorectal cancer (CRC) genes, identified several potential causal genes, including RPS20, IL12RB1, LIMK2, POLE2, MRE11, POT1, FAN1, WIF1, HNRNPA0, SEMA4A, FOCAD, PTPN12, LRP6, POLQ, BLM and MCM9, and the epigenetic inactivation of PTPRJ. Here we attempted to validate the association between variants in these genes and nonpolyposis CRC by performing a mutational screening of the genes and PTPRJ promoter methylation analysis in 473 familial/early-onset CRC cases, a systematic review of the published cases, and assessment of allele frequencies in control population. In the studied cohort, 24 (5%) carriers of (predicted) deleterious variants in the studied genes and no constitutional PTPRJ epimutations were identified. Read More

BMC Cancer 2020 May 24;20(1):460. Epub 2020 May 24.

Institute for Medical Informatics, Statistics and Epidemiology (IMISE), University of Leipzig, Leipzig, Germany.

Background: Individuals with pathogenic germline variants in DNA mismatch repair (MMR) genes are at increased risk of developing colorectal, endometrial and other cancers (Lynch syndrome, LS). While previous studies have extensively described cancer risks in LS, cancer risks in individuals from families without detectable MMR gene defects despite MMR deficiency (Lynch-like syndrome, LLS), and in individuals from families fulfilling the Amsterdam-II criteria without any signs of MMR deficiency (familial colorectal cancer type X, FCCX) are less well studied. The aim of this prospective study was to characterise the risk for different cancer types in LS, LLS, and FCCX, and to compare these with the cancer risks in the general population. Read More

Carcinogenesis 2020 May 23. Epub 2020 May 23.

Laboratory of Veterinary Pathology, Gifu University, Yanagido, Gifu, Japan.

Many hereditary disorders in dogs have equivalents in humans and thus attract attention as natural animal models. Breed predisposition to certain diseases often provides promising clues to explore novel hereditary disorders in dogs. Recently, cases of gastrointestinal (GI) polyps in Jack Russell Terriers (JRTs) have increased in Japan. Read More

Hum Mutat 2020 May 22. Epub 2020 May 22.

Ambry Genetics, Aliso Viejo, California, USA.

Purpose: Multi-gene panel testing for cancer predisposition mutations is becoming routine in clinical care. However, the gene content of panels offered by testing laboratories vary significantly, and data on mutation detection rates by gene and by panel is limited, causing confusion among clinicians on which test to order.

Methods: Using results from 147,994 multi-gene panel tests conducted at Ambry Genetics, we built an interactive prevalence tool to explore how differences in ethnicity, age of onset, and personal and family history of different cancers affect the prevalence of pathogenic mutations in 31 cancer predisposition genes, across various clinically available hereditary cancer gene panels. Read More

Colorectal Dis 2020 May 22. Epub 2020 May 22.

Department of Gastroenterological Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Aim: The aim was to evaluate the timing of prophylactic colectomy in patients with familial adenomatous polyposis (FAP) in Finland.

Method: All Finnish FAP patients were included from the years 1963-2018. Among the 452 FAP patients studied, 252 were called up as relatives of the proband. Read More

ACS Case Rev Surg 2019 Apr;2(4):13-17

Northwestern Memorial Hospital, 251 East Huron Street, Chicago IL 60611.

Background: A 59-year-old woman with strong family history of early-age colorectal cancer was found to have synchronous tubular adenomas of the duodenum and transverse colon during surveillance endoscopy 12 years after undergoing right colectomy and adjuvant chemotherapy for stage II colon adenocarcinoma. The duodenal lesion was endoscopically unresectable due to central depression, and the transverse colon adenoma was unresectable because it was confluent with the previous ileocolic anastomosis. Given the synchronous unresectable lesions in the setting of an Amsterdam positive kindred, the patient underwent simultaneous pancreaticoduodenectomy and completion total abdominal colectomy with ileorectal anastomosis. Read More

Int J Clin Oncol 2020 May 19. Epub 2020 May 19.

Unit of Hereditary Digestive Tract Tumours, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, via Venezian, 1, 20133, Milan, Italy.

Background: Risk factors for metachronous colorectal cancer (mCRC) in Lynch Syndrome (LS) patients are essential for colorectal cancer (CRC) treatment strategy to perform not only a curative but also preventive surgery. The aim of this study was to evaluate the risk factors for mCRC development in LS patients to define the patient subset that may benefit an extended curative and preventive surgical resection.

Methods: Patient's clinical history, oncological, molecular and follow-up were collected retrospectively from the Hereditary Digestive Tumors Registry at the National Cancer Institute of Milan. Read More

Clin Transl Oncol 2020 May 16. Epub 2020 May 16.

Department of Pathology, University of Valencia, Hospital Clínico Universitario de Valencia, CIBERONC, Valencia, Spain.

In this update of the consensus of the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica-SEOM) and the Spanish Society of Pathology (Sociedad Española de Anatomía Patológica-SEAP), advances in the analysis of biomarkers in advanced colorectal cancer (CRC) as well as susceptibility markers of hereditary CRC and molecular biomarkers of localized CRC are reviewed. Recently published information on the essential determination of KRAS, NRAS and BRAF mutations and the convenience of determining the amplification of human epidermal growth factor receptor 2 (HER2), the expression of proteins in the DNA repair pathway and the study of NTRK fusions are also evaluated. From the pathological point of view, the importance of analysing the tumour budding and poorly differentiated clusters, and its prognostic value in CRC is reviewed, as well as the impact of molecular lymph node analysis on lymph node staging in CRC. Read More

Acta Med Port 2020 May 4;33(5):297-304. Epub 2020 May 4.

Medical Faculty. University of Porto. Porto. Instituto de Investigação e Inovação em Saúde. Universidade do Porto. Porto. Institute of Molecular Pathology and Immunology. Universidade do Porto. Porto. Department of Pathology. Medical Faculty. University of Porto. Porto. Portugal.

Introduction: Overcoming immunosurveillance is a major step in the progression of many types of tumors. Several immune escape strategies have been identified, including immunoediting and the establishment of an immune suppressive microenvironment. The aim of the present study was to determine whether the hereditary or sporadic context has any influence in the relationship between immune surveillance and tumor development, using sporadic and familial adenomatous polyposis related colorectal adenomas as a model. Read More

J Gastrointest Surg 2020 May 14. Epub 2020 May 14.

Department of General Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, A100, Cleveland, OH, 44195, USA.

Background: Pancreas-sparing duodenectomy (PSD) offers definitive therapy for duodenal polyposis associated with familial adenomatous polyposis (FAP). We reviewed the long-term complications of PSD and evaluated the incidence of high-grade dysplasia (HGD) and cancer in the remaining upper gastrointestinal tract.

Methods: Forty-seven FAP patients with duodenal polyposis undergoing PSD from 1992 to 2019 were reviewed. Read More

Surg Clin North Am 2020 Jun 16;100(3):483-498. Epub 2020 Apr 16.

Department of Surgery, St. Vincent's Medical Center, Bridgeport, CT, USA; Frank H. Netter MD School of Medicine, Quinnipiac University, North Haven, CT, USA. Electronic address:

For most individuals, cancer development is multifactorial; however, up to 10% of all cancers are related to an inherited genetic mutation. As health care shifts to having a greater emphasis on prevention, care providers, including general surgeons, will need to play a role in identifying patients at high risk for cancer development. Genetic testing provides a tool to determine those patients with a genetic mutation and to whom appropriate preventive care and treatment may be offered. Read More

Genet Med 2020 May 13. Epub 2020 May 13.

Institute for Medical Genetics and Pathology, University Hospital Basel, and Research Group Human Genomics, Department of Research, University of Basel, Basel, Switzerland.

Purpose: Juvenile polyposis syndrome (JPS) is a rare, autosomal-dominantly inherited cancer predisposition caused in approximately 50% of cases by pathogenic germline variants in SMAD4 and BMPR1A. We aimed to gather detailed clinical and molecular genetic information on JPS disease expression to provide a basis for management guidelines and establish open access variant databases.

Methods: We performed a retrospective, questionnaire-based European multicenter survey on and established a cohort of SMAD4/BMPR1A pathogenic variant carriers from the medical literature. Read More

Tumori 2020 May 11:300891620919171. Epub 2020 May 11.

Department of Medical Oncology, Trakya University Faculty of Medicine, Edirne, Turkey.

Background: Recent advances in next-generation sequencing (NGS) technology have enabled multigene testing and changed the diagnostic approach to hereditary gastrointestinal cancer/polyposis syndromes. The aim of this study was to analyze different cancer predisposition genes in hereditary/sporadic gastrointestinal cancer/polyposis.

Methods: Cancer predisposition genes were analyzed with an Illumina MiSeq NGS system in 80 patients with gastrointestinal cancer/polyposis who were examined between the years 2016 and 2019. Read More

Medicine (Baltimore) 2020 May;99(19):e20124

Department of Pathology and Laboratory Medicine.

Recent studies have suggested an increased risk of prostate cancer in men with Lynch syndrome driven by germline mutations in mismatch repair (MMR) genes. However, the incidence and clinical implication of MMR deficiency in sporadic prostate cancers remain poorly understood. We immunohistochemically stained for MLH1, MSH2, MSH6, and PMS2 in a set of tissue microarray consisting of 220 radical prostatectomy specimens and evaluated the relationship between loss of their expression and available clinicopathological features. Read More

Gastrointest Endosc 2020 May 4. Epub 2020 May 4.

Department of Gastroenterology, Hepatology and Nutrition,; Department of Colorectal Surgery,; Sanford R. Weiss, MD, Center for Hereditary Colorectal Neoplasia, Cleveland Clinic.

Background And Aims: Gastric cancer is an extracolonic manifestation of familial adenomatous polyposis (FAP) and associated with high-risk gastric polyps. There are no known endoscopic criteria to identify these high-risk polyps. Our aim was to develop endoscopic criteria to identify high-risk polyps on endoscopy in FAP. Read More

Jpn J Clin Oncol 2020 May 7. Epub 2020 May 7.

Graduate School of Medicine, Intractable Disease Research Center, Juntendo University, Tokyo, Japan.

Hereditary mixed polyposis syndrome (HMPS) is a rare autosomal dominant disorder characterized by a mixture of typical and/or atypical juvenile polyps, adenomas and hyperplastic polyps, resulting in an increased risk of colorectal cancer. In HMPS, four different germline BMPR1A variants from five unrelated families have been reported. This study is the first to report HMPS within a Japanese family. Read More

BMC Gastroenterol 2020 May 6;20(1):136. Epub 2020 May 6.

Department of Medical Oncology, Guangxi Medical University Cancer Hospital, No.71, Hedi road, Nanning, 530021, PR China.

Background: Tumor-to-tumor metastasis is a rare event. Rectal cancer to primary thyroid neoplasm metastasis is extremely rare. Herein, we reported a case of metastatic rectal adenocarcinoma to a papillary thyroid carcinoma. Read More

Hered Cancer Clin Pract 2020 29;18:10. Epub 2020 Apr 29.

1Clinica Oncologica, Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona Umberto I G M Lancisi G Salesi, Ancona, Italy.

Background: Hereditary non-polyposis colorectal cancer (HNPCC) and Hereditary Breast and Ovarian Cancer Syndrome (HBOC) are the most common hereditary cancer syndromes in which a genetic test is available. Potential risks associated with testing include psychological harm, emotional distress and insurance problems.

Methods: The aim of the present study is to investigate determinants of distress in a sample of Italian subjects undergoing genetic counseling. Read More

Hered Cancer Clin Pract 2020 28;18. Epub 2020 Apr 28.

1Prenetics Limited, 7/F, Prosperity Millennia Plaza, 663 King's Road, Quarry Bay, Hong Kong SAR, China.

Background: Understanding the genetic basis of cancer risk is a major international endeavor. The emergence of next-generation sequencing (NGS) in late 2000's has further accelerated the discovery of many cancer susceptibility genes. The use of targeted NGS-based multigene testing panels to provide comprehensive analysis of cancer susceptible genes has proven to be a viable option, with the accurate and robust detection of a wide range of clinically relevant variants in the targeted genes being crucial. Read More

Bull Cancer 2020 May 1;107(5):586-600. Epub 2020 May 1.

PSL Research University, Institut Curie, département de génétique, 26, rue d'Ulm, 75248 Paris cedex 05, France. Electronic address:

MUTYH-associated polyposis (MUTYH-associated polyposis, MAP) is an autosomal recessive inheritance disorder related to bi-allelic constitutional pathogenic variants of the MUTYH gene which was first described in 2002. In 2011, a group of French experts composed of clinicians and biologists, performed a summary of the available data on this condition and drew up recommendations concerning the indications and the modalities of molecular analysis of the MUTYH gene in index cases and their relatives, as well as the management of affected individuals. In view of recent developments, some recommendations have become obsolete, in particular with regard to the molecular analysis strategy since MUTYH gene has been recently included in a consensus panel of 14 genes predisposing to colorectal cancer. Read More

AJNR Am J Neuroradiol 2020 05 30;41(5):904-910. Epub 2020 Apr 30.

From the Department of Radiology (A.K., M.S., S.S., C.H.), Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.

Background And Purpose: Constitutional mismatch repair deficiency is a hereditary childhood cancer predisposition syndrome characterized by brain tumors and colorectal and hematologic malignancies. Our objective was to describe the neuroimaging findings in patients with constitutional mismatch repair deficiency.

Materials And Methods: This retrospective study included 14 children with genetically confirmed constitutional mismatch repair deficiency who were referred to 2 tertiary pediatric oncology centers. Read More

JAMA Netw Open 2020 Apr 1;3(4):e203959. Epub 2020 Apr 1.

Division of Cardiology and Center for Genomic Medicine, Department of Medicine, Massachusetts General Hospital, Boston.

Importance: Pathogenic DNA variants associated with familial hypercholesterolemia, hereditary breast and ovarian cancer syndrome, and Lynch syndrome are widely recognized as clinically important and actionable when identified, leading some clinicians to recommend population-wide genomic screening.

Objectives: To assess the prevalence and clinical importance of pathogenic or likely pathogenic variants associated with each of 3 genomic conditions (familial hypercholesterolemia, hereditary breast and ovarian cancer syndrome, and Lynch syndrome) within the context of contemporary clinical care.

Design, Setting, And Participants: This cohort study used gene-sequencing data from 49 738 participants in the UK Biobank who were recruited from 22 sites across the UK between March 21, 2006, and October 1, 2010. Read More

Int J Colorectal Dis 2020 Jul 21;35(7):1273-1282. Epub 2020 Apr 21.

Center for Colorectal Cancer, National Cancer Center, Research Institute and Hospital, 323, Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 10408, Republic of Korea.

Purpose: The high incidence of metachronous colorectal tumours in patients with hereditary non-polyposis colorectal cancer (HNPCC) encourages extended resection (ER); however, the optimal surgical approach remains unclear. We evaluated the incidences of metachronous colorectal neoplasms following curative colorectal cancer segmental resection (SR) vs ER in patients with HNPCC and investigated patients' oncologic outcomes according to surgical modality and mismatch repair status.

Methods: We retrospectively investigated medical records of patients with HNPCC (per the Amsterdam II criteria) treated for primary colon cancer at our institution between 2001 and 2017. Read More

Clin Genitourin Cancer 2020 Mar 13. Epub 2020 Mar 13.

Institute of Pathology, University Medicine Rostock, Rostock, Germany.

Background: Upper tract urothelial carcinoma (UTUC) may arise in the setting of hereditary non-polyposis colorectal cancer (Lynch syndrome [LS]) or sporadically. Variable frequencies of microsatellite instability (MSI) were found in UTUC. For advanced solid MSI tumors, targeted therapy with programmed death-ligand 1 inhibitors is available. Read More