Patient-reported burden of intensified surveillance and surgery in high-risk individuals under pancreatic cancer surveillance
In conclusion, in individuals at high risk for pancreatic cancer, intensified surveillance temporarily increased cancer worries, without affecting general anxiety or depression. Although pancreatic surgery led to substa ntial co-morbidity, quality of life was similar to the general population, and surgery did not negatively affect the attitude towards surveillance. (Source: Familial Cancer)
Source: Familial Cancer - March 18, 2020 Category: Cancer & Oncology Source Type: research
Lack of evidence for CDK12 as an ovarian cancer predisposing gene
AbstractCDK12 variants were investigated as a genetic susceptibility to ovarian cancer in a series of 416 unrelated and consecutive patients with ovarian carcinoma and who carry neither germlineBRCA1 norBRCA2 pathogenic variant. The presence ofCDK12 variants was searched in germline DNA by massive parallel sequencing on pooled DNAs. The lack of detection of deleterious variants and the observed proportion of missense variants in the series of ovarian carcinoma patients as compared with all human populations strongly suggests thatCDK12 is not an ovarian cancer predisposing gene. (Source: Familial Cancer)
Source: Familial Cancer - March 13, 2020 Category: Cancer & Oncology Source Type: research
Collaborative Group of the Americas on Inherited Gastrointestinal Cancer Position statement on multigene panel testing for patients with colorectal cancer and/or polyposis
AbstractMultigene panel tests for hereditary cancer syndromes are increasingly utilized in the care of colorectal cancer (CRC) and polyposis patients. However, widespread availability of panels raises a number of questions including which patients should undergo testing, which genes should be included on panels, and the settings in which panels should be ordered and interpreted. To address this knowledge gap, key questions regarding the major issues encountered in clinical evaluation of hereditary CRC and polyposis were designed by the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer Position Statem...
Source: Familial Cancer - March 13, 2020 Category: Cancer & Oncology Source Type: research
Do the risks of Lynch syndrome-related cancers depend on the parent of origin of the mutation?
AbstractIndividuals who carry pathogenic mutations in DNA mismatch repair (MMR) genes have high risks of cancer, and small studies have suggested that these risks depend on the sex of the parent from whom the mutation was inherited. We have conducted the first large study of such a parent-of-origin effect (POE). Our study was based on all MMR gene mutation carriers and their relatives in the Colon Cancer Family Registry, comprising 18,226 people. The POE was estimated as a hazard ratio (HR) using a segregation analysis approach that adjusted for ascertainment. HR = 1 corresponds to no POE and HR > 1 correspond...
Source: Familial Cancer - February 26, 2020 Category: Cancer & Oncology Source Type: research
Perceptions of risk and reward in BRCA1 and BRCA2 mutation carriers choosing salpingectomy for ovarian cancer prevention
In conclusion, mostBRCA mutation carriers undergoing risk-reducing salpingectomy are satisfied with their decision and have lower risk perception after salpingectomy, though some older mutation carriers did not plan on future oophorectomy. Salpingectomy with delayed oophorectomy inBRCA mutation carriers remains investigational and should preferably be performed within a clinical trial to prevent introduction of an innovation before safety has been proven. (Source: Familial Cancer)
Source: Familial Cancer - February 23, 2020 Category: Cancer & Oncology Source Type: research
Increased prevalence of Barrett ’s esophagus in patients with MUTYH -associated polyposis (MAP)
AbstractBarrett ’s oesophagus (BE) has been associated with an increased risk of both colorectal adenomas and colorectal cancer. A recent investigation reported a high frequency of BE in patients with adenomatous polyposis coli (APC)-associated polyposis (FAP). The aim of the present study is to evaluate the prevalence of BE in a large cohort of patients withMUTYH-associated polyposis (MAP) andAPC-associated adenomatous polyposis. Patients with a genetically confirmed diagnosis of familial adenomatous polyposis (FAP) or MAP were selected and upper gastrointestinal (GI) endoscopy reports, pathology reports of upper GI bio...
Source: Familial Cancer - February 21, 2020 Category: Cancer & Oncology Source Type: research
Mismatch repair gene pathogenic germline variants in a population-based cohort of breast cancer
AbstractThe advent of gene panel testing is challenging the previous practice of using clinically defined cancer family syndromes to inform single-gene genetic screening. Individual and family cancer histories that would have previously indicated testing of a single gene or a small number of related genes are now, increasingly, leading to screening across gene panels that contain larger numbers of genes. We have a pplied a gene panel test that included four DNA mismatch repair (MMR) genes (MLH1,MSH2,MSH6 andPMS2) to an Australian population-based case –control-family study of breast cancer. Altogether, eight pathogeni...
Source: Familial Cancer - February 13, 2020 Category: Cancer & Oncology Source Type: research
Novel intronic variant in PALB2 gene and effective prevention of Fanconi anemia in family
AbstractDespite the acceptance of NextGen sequencing as a diagnostic modality suitable for probands and carriers of Mendelian diseases, its efficiency in identifying causal mutations is limited by both technical aspects of variant call algorithms and by imperfect, consensus-based criteria for assessing the pathogenicity of the findings. Here we describe the medical history of the family with a child born with Fanconi anemia. In this case, typical diagnostic routines were complicated by unusual combination of mutations.PALB2 variant NM_024675.3:c.172_175delTTGT (p.Gln60Argfs) in maternal sample, previously classified as a d...
Source: Familial Cancer - February 11, 2020 Category: Cancer & Oncology Source Type: research
Co-occurrence of multiple endocrine neoplasia type 4 and spinal neurofibromatosis: a case report
AbstractMultiple Endocrine Neoplasia (MEN) type 4 is a rare genetic condition that results from variants of theCDKN1B gene and predisposes individuals to develop endocrine tumors. Spinal neurofibromatosis (SNF) is an uncommon subtype of neurofibromatosis type 1 (NF1) characterized by bilateral neurofibromas of all spinal roots. Here we report a case of the co-occurrence of these syndromes, which has not yet been described in the literature. A male in his 60s presented with Gleason 5 + 4 localized prostate adenocarcinoma treated with radical prostatectomy. Two years later, he developed liver and bone metastasis consist...
Source: Familial Cancer - February 11, 2020 Category: Cancer & Oncology Source Type: research
Missense PALB2 germline variant disrupts nuclear localization of PALB2 in a patient with breast cancer
In conclusion, our studies provided the functional evidence showing the deleterious effect of c.3251C>T, and non-deleterious effects of c.1054G>C and c.1057A>G. Using the ClinGen Pathogenicity calculator, c.3251C>T remains a VUS while c.1054G>C and c.1057A>G may be classified as likely benign variants. (Source: Familial Cancer)
Source: Familial Cancer - February 10, 2020 Category: Cancer & Oncology Source Type: research
Abstracts of the 4th meeting of the European Hereditary Tumour Group, Barcelona, Spain, October 17 –19th, 2019
(Source: Familial Cancer)
Source: Familial Cancer - February 6, 2020 Category: Cancer & Oncology Source Type: research
Prevalence of CNV-neutral structural genomic rearrangements in MLH1, MSH2, and PMS2 not detectable in routine NGS diagnostics
AbstractRoutine diagnostics for colorectal cancer patients suspected of having Lynch-Syndrome (LS) currently uses Next-Generation-Sequencing (NGS) of targeted regions within the DNA mismatch repair (MMR) genes. This analysis can reliably detect nucleotide alterations and copy-number variations (CNVs); however, CNV-neutral rearrangements comprising gene inversions or large intronic insertions remain undetected because their breakpoints are usually not covered. As several founder mutations exist for LS, we established PCR-based screening methods for five known rearrangements inMLH1,MSH2, orPMS2, and investigated their preval...
Source: Familial Cancer - January 29, 2020 Category: Cancer & Oncology Source Type: research
Mainstreamed genetic testing of breast cancer patients in two hospitals in South Eastern Norway
AbstractStudies have shown that a significant number of eligible breast cancer patients are not offered genetic testing or referral to genetic counseling. To increase access to genetic testing in South Eastern Norway, testing has since 2014 been offered directly to breast cancer patients by surgeons and oncologists. This practice is termed “mainstreamed genetic testing”. The aim of this study was to investigate to what extent patients in South Eastern Norway are offered testing. Three hundred and sixty one patients diagnosed in 2016 and 2017 at one regional and one university hospital in South Eastern Norway were inclu...
Source: Familial Cancer - January 29, 2020 Category: Cancer & Oncology Source Type: research
Detection of DNA mismatch repair deficient crypts in random colonoscopic biopsies identifies Lynch syndrome patients
In conclusion, MMR deficient crypts are a specific biomarker of LS and can be identified in random normal mucosal biopsies in LS patients. Evaluation for MMR deficient crypts in colonoscopic biopsies of normal mucosa can help identify LS patients. (Source: Familial Cancer)
Source: Familial Cancer - January 28, 2020 Category: Cancer & Oncology Source Type: research
Factors associated with decision-making on prophylactic hysterectomy and attitudes towards gynecological surveillance among women with Lynch syndrome (LS): a descriptive study
AbstractTo prevent endometrial carcinoma in Lynch syndrome (LS), regular gynecological surveillance visits and prophylactic surgery are recommended. Previous data have shown that prophylactic hysterectomy is an effective means of cancer prevention, while the advantages and disadvantages of surveillance are somewhat unclear. We aimed to evaluate female LS carriers ’ attitudes towards regular gynecological surveillance and factors influencing their decision-making on prophylactic surgery that have not been well documented. Pain experienced during endometrial biopsies was also evaluated. Postal questionnaires were sent to L...
Source: Familial Cancer - January 28, 2020 Category: Cancer & Oncology Source Type: research
