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
Balancing the burden and benefits of colonoscopy in Lynch Syndrome
(Source: Familial Cancer)
Source: Familial Cancer - September 15, 2023 Category: Cancer & Oncology Source Type: research
PREMM5 distinguishes sporadic from Lynch syndrome-associated MMR-deficient/MSI-high colorectal cancer
AbstractCurrent algorithms for diagnosing Lynch syndrome (LS) include multistep molecular tumor tests to distinguish LS-associated from sporadic colorectal cancer (CRC), which add cost and complexity to the evaluation. We hypothesized that PREMM5, a clinical LS prediction tool, could be an alternative approach to screen for LS, thereby lessening the need for specialized molecular diagnostics. We reviewed a consecutively ascertained institutional cohort of 1058 CRC patients on whom pathologic and clinical data were available, including prior LS germline testing. Data from MMR-D/MSI-H CRC patients were reviewed and PREMM5 sc...
Source: Familial Cancer - August 12, 2023 Category: Cancer & Oncology Source Type: research
Combining clinical and molecular characterization of CDH1: a multidisciplinary approach to reclassification of a splicing variant
In conclusion, we report the first case of theCDH1 c.833-9 C > G intronic variant being associated with DGLBC and illustrate how collaboration among clinicians, laboratory personnel, and patients is crucial for variant resolution. (Source: Familial Cancer)
Source: Familial Cancer - August 4, 2023 Category: Cancer & Oncology Source Type: research
Prevalence and genetic spectrum associated with hereditary colorectal cancer syndromes, the need to improve cancer risk awareness, and family cascade testing in Vietnam
This study aims to define the mutation spectrum associated with hereditary colorectal cancer syndromes (HCCS) in Vietnam, evaluate the influence of genetic testing on carriers’ awareness, and also investigate the barriers in familial testing. Genetic te st reports were collected to identify HCCS cases, then cases underwent a survey investigating self-risk and familial-risk awareness, proactive cancer screening, and familial testing barriers. Participant characteristics, mutation prevalence, and results from the survey were descriptively analyzed an d reported. Of all genetic test results, 3% (49/1632) were identified wit...
Source: Familial Cancer - July 30, 2023 Category: Cancer & Oncology Source Type: research
Germline whole genome sequencing in adults with multiple primary tumors
AbstractMultiple primary tumors (MPTs) are a harbinger of hereditary cancer syndromes. Affected individuals often fit genetic testing criteria for a number of hereditary cancer genes and undergo multigene panel testing. Other genomic testing options, such as whole exome (WES) and whole genome sequencing (WGS) are available, but the utility of these genomic approaches as a second-tier test for those with uninformative multigene panel testing has not been explored. Here, we report our germline sequencing results from WGS in 9 p atients with MPTs who had non-informative multigene panel testing. Following germline WGS, sequ...
Source: Familial Cancer - July 22, 2023 Category: Cancer & Oncology Source Type: research
Mainstreamed genetic testing of breast cancer patients: experience from a single surgeon ’s practice in a large US Academic Center
This study evaluated the impact of mainstreamed genetic testing (MGT) on the timing and uptake of testing in an academic breast surgeon ’s practice. Before September 2019 (pre-MGT phase), a breast surgery practice at Massachusetts General Hospital followed a traditional model of a pre-test consultation with a genetic counselor (GC) following a referral. After September 2019 (post-MGT phase), the same practice offered patients gene tic testing in a single clinical encounter with a breast surgeon. We evaluated the waiting time between referral and GC visit in the pre-MGT phase and compared the uptake and positivity rates b...
Source: Familial Cancer - June 24, 2023 Category: Cancer & Oncology Source Type: research
Whole genome sequencing and disease pattern in patients with juvenile polyposis syndrome: a nationwide study
AbstractJuvenile polyposis syndrome (JPS) is a hereditary hamartomatous polyposis syndrome characterized by gastrointestinal juvenile polyps and increased risk of gastrointestinal cancer. Germline pathogenic variants are detected inSMAD4 orBMPR1A, however in a significant number of patients with JPS, the etiology is unknown. From Danish registers, and genetic department and laboratories, we identified all patients in Denmark with a clinical diagnosis of JPS and/or a pathogenic variant inBMPR1A orSMAD4. In patients where no variant had been detected, we performed genetic analysis, including whole genome sequencing. We colle...
Source: Familial Cancer - June 24, 2023 Category: Cancer & Oncology Source Type: research
Willingness of individuals with Li-Fraumeni syndrome to participate in a cancer prevention trial: a survey study
(Source: Familial Cancer)
Source: Familial Cancer - June 23, 2023 Category: Cancer & Oncology Source Type: research
