Cascade screening in HBOC and Lynch syndrome: guidelines and procedures in a UK centre
We present time trends (1990 –2020) of identification of index cases with germline CPG variants and numbers of subsequent cascade tests, forBRCA1,BRCA2, and the Lynch genes (MLH1,MSH2,MSH6 andPMS2). ForBRCA1/2 there was a definite increase in the proportion of index cases with ovarian cancer only and pre-symptomatic index tests both doubling from 16 to 32% and 3.2 to  >  8% respectively. A mean of 1.73–1.74 additional family tests were generated for eachBRCA1/2 index case within 2 years. Overall close to one positive cascade test was generated per index case resulting in  >  1000 risk reducing surgery ope...
Source: Familial Cancer - March 13, 2024 Category: Cancer & Oncology Source Type: research

In Memoriam: Steffen B ülow (1943–2023)
(Source: Familial Cancer)
Source: Familial Cancer - March 13, 2024 Category: Cancer & Oncology Source Type: research

Can our experience with surveillance for inherited pancreatic cancer help to identify early pancreatic cancer in the general population?
AbstractScreening of the general population for cancer is a matter of primary prevention reducing the burden of disease. Whilst this is successful for several cancers including breast, colon and prostate, the situation to screen and hence prevent pancreatic cancer is different. The organ is not as accessible to simple physical exam or biological samples (fecal or blood test). Neither exists a blood test such as PSA that is cost-effective. Reviewing the evidence from screening risk groups for pancreatic cancer, one must conclude that there is no rational at present to screen the general population, for a lack of appropriate...
Source: Familial Cancer - March 5, 2024 Category: Cancer & Oncology Source Type: research

Familial pancreatic cancer: a long fruitful journey
AbstractIn the early years of my GI fellowship, a healthy 40-year-old man came to my clinic and announced that he was going to die of pancreatic cancer. His brothers, father and uncles had all died of the disease; he felt his fate was inescapable. I asked whether his family members had seen doctors or had any tests. His answer was yes to both. Even so, doctors could not diagnose the pancreatic cancer at early stages. CT scans were always negative. I thought to myself, in order to help this patient —CT scans may not be reliable for early detection. Perhaps other methods of imaging the pancreas might be of more benefit. Th...
Source: Familial Cancer - March 4, 2024 Category: Cancer & Oncology Source Type: research

Precursor lesions in familial and hereditary pancreatic cancer
AbstractInfiltrating ductal adenocarcinoma of the pancreas, referred to here as “pancreatic cancer,” is one of the deadliest of all of the solid malignancies. The five-year survival rate in the United States for individuals diagnosed today with pancreatic cancer is a dismal 12%. Many invasive cancers, including pancreatic cancer, however, arise from histologically and genet ically well-characterized precursor lesions, and these precancers are curable. Precursor lesions therefore are an attractive target for early detection and treatment. This is particularly true for individuals with an increased risk of developing inv...
Source: Familial Cancer - February 6, 2024 Category: Cancer & Oncology Source Type: research

CGA-IGC 2023 Abstracts
(Source: Familial Cancer)
Source: Familial Cancer - February 4, 2024 Category: Cancer & Oncology Source Type: research

Aberrant transcription caused by an intronic non-canonical CDH1 variant
(Source: Familial Cancer)
Source: Familial Cancer - February 4, 2024 Category: Cancer & Oncology Source Type: research

Low prevalence of gastric intestinal metaplasia and Helicobacter pylori on surveillance upper endoscopy in Lynch syndrome
AbstractLynch syndrome (LS) increases the risk of numerous different cancers including gastric cancer. While some current guidelines recommend empiric gastric biopsies be performed during upper gastrointestinal cancer surveillance in Lynch syndrome (LS), the yield of these biopsies and the prevalence of gastric intestinal metaplasia (GIM) andHelicobacter pylori (HP) in LS remains unknown. Herein we analyze 165 consecutive individuals with LS who underwent upper endoscopic surveillance with biopsies of the gastric antrum and body being performed universally in all individuals. Of the study cohort, 6.7% of universally biopsi...
Source: Familial Cancer - January 31, 2024 Category: Cancer & Oncology Source Type: research

High amount of fertility reducing tumors and procedures, but no evidence for premature ovarian failure in female Lynch syndrome patients
AbstractLynch syndrome (LS; HNPCC) patients carry heterozygous pathogenic germline variants in mismatch repair (MMR) genes, which have also been shown to play an important role in meiosis. Therefore, it was hypothesized, that LS might be associated with a higher risk for premature ovarian failure (POF) or earlier menopause. Data on medical gynaecological history, cancer diagnoses and therapy were collected from 167 female LS patients and compared to a population-based control cohort. There was no difference between the age of menopause in patients compared to controls and no evidence for a higher risk of POF in LS patients...
Source: Familial Cancer - January 27, 2024 Category: Cancer & Oncology Source Type: research

Breast density in NF1 women: a retrospective study
AbstractNeurofibromatosis type 1 (NF1) is an autosomal dominant condition caused by neurofibromin haploinsufficiency due to pathogenic variants in theNF1 gene. Tumor predisposition has long been associated with NF1, and an increased breast cancer (BC) incidence and reduced survival have been reported in recent years for women with NF1. As breast density is another known independent risk factor for BC, this study aims to evaluate the variability of breast density in patients with NF1 compared to the general population. Mammograms from 98 NF1 women affected by NF1, and enrolled onto our monocentric BC screening program, were...
Source: Familial Cancer - January 25, 2024 Category: Cancer & Oncology Source Type: research

Li Fraumeni Syndrome predisposes to gastro-esophageal junction tumours
AbstractLi-Fraumeni Syndrome (LFS), caused by germline pathogenic variants inTP53, predisposes to a wide range of young-onset malignancies, particularly sarcoma, breast and brain cancer. More recently, an increased risk of gastric adenocarcinoma has been recognised, although uptake of surveillance upper endoscopy is unclear. Our retrospective review of 65 patients with LFS, of whom 53.8% had undergone endoscopy, identified four patients (6.2%) with gastro-esophageal junction (GEJ) adenocarcinomas. Two cases were found on asymptomatic screening and were early stage. No cases had family history of gastrointestinal malignancy...
Source: Familial Cancer - January 11, 2024 Category: Cancer & Oncology Source Type: research

Cascade genetic counseling and testing in hereditary syndromes: inherited cardiovascular disease as a model: a narrative review
AbstractInherited cardiovascular diseases cover the inherited cardiovascular disease familial hypercholesterolemia and inherited cardiac diseases, like inherited cardiomyopathies and inherited arrhythmia syndromes. Cascade genetic counseling and testing in inherited cardiovascular diseases have had three decades of academic attention. Inherited cardiovascular diseases affect around 1 –2% of the population worldwide and cascade genetic counseling and testing are considered valuable since preventive measures and/or treatments are available. Cascade genetic counseling via a family-mediated approach leads to an uptake of gen...
Source: Familial Cancer - January 6, 2024 Category: Cancer & Oncology Source Type: research

Inherited BRCA1 and RNF43 pathogenic variants in a familial colorectal cancer type X family
We describe a multi-generation CRC-affected family segregating pathogenic variants in bothBRCA1, a gene associated with breast and ovarian cancer andRNF43, a gene associated with Serrated Polyposis Syndrome (SPS). A single family out of 105 families meeting the criteria for FCCTX (Amsterdam I family history criteria with mismatch repair (MMR)-proficient CRCs) recruited to the Australasian Colorectal Cancer Family Registry (ACCFR; 1998 –2008) that underwent whole exome sequencing (WES), was selected for further testing. CRC and polyp tissue from four carriers were molecularly characterized including a single CRC that unde...
Source: Familial Cancer - December 8, 2023 Category: Cancer & Oncology Source Type: research

Cascade testing in Italian Hereditary Breast Ovarian Cancer families: a missed opportunity for cancer prevention?
AbstractHealthy carriers ofBRCA1/2 pathogenic variants (PVs) may benefit from risk-reducing measures of proven efficacy. The main approach to identify these individuals is cascade testing, and strategies to support this complex process are under investigation. In Italy, cascade testing has received little attention; therefore, we analyzed the uptake and characteristics ofBRCA1/2 cascade testing in families diagnosed with HBOC between 2017 and 2019 at two Italian genetics centers. All blood relatives aged 18 years or older at September 2022 and who could be involved in the first step of cascade testing (i.e., all the living...
Source: Familial Cancer - November 16, 2023 Category: Cancer & Oncology Source Type: research

Functional and phenotypic consequences of an unusual inversion in MSH2
AbstractLynch syndrome is an autosomal dominant disorder that usually results from a pathogenic germline variant in one of four genes (MSH2,MSH6,MLH1,PMS2) involved in DNA mismatch repair. Carriers of such variants are at risk of developing numerous cancers during adulthood. Here we report on a family suspected of having Lynch syndrome due to a history of endometrial adenocarcinoma, ovarian clear cell carcinoma, and adenocarcinoma of the duodenum in whom we identified a germline 29 nucleotide in-frame inversion in exon 3 ofMSH2. We further show that this variant is almost completely absent at the protein level, and that th...
Source: Familial Cancer - November 14, 2023 Category: Cancer & Oncology Source Type: research