The psychological impact and experience of breast cancer screening in young women with an increased risk of breast cancer due to neurofibromatosis type 1
AbstractWomen with neurofibromatosis type 1 (NF1) have an increased risk of developing early breast cancer with a poorer prognosis compared to the general population. Therefore, international management guidelines recommend regular screening in women with NF1 starting from 30 to 35 years. As the psychological impacts of breast cancer screening in other high-risk populations cannot be extended to women with NF1, due to increased incidence of cognitive and mental health issues, the psychological harms of breast screening in women with NF1 are unknown. Co nsequently, the aim of this study was to assess the psychological imp...
Source: Familial Cancer - May 8, 2021 Category: Cancer & Oncology Source Type: research
The clinical features of polymerase proof-reading associated polyposis (PPAP) and recommendations for patient management
AbstractPathogenic germline exonuclease domain (ED) variants of POLE and POLD1 cause the Mendelian dominant condition polymerase proof-reading associated polyposis (PPAP). We aimed to describe the clinical features of all PPAP patients with probably pathogenic variants. We identified patients with a variants mapping to the EDs ofPOLE orPOLD1 from cancer genetics clinics, a colorectal cancer (CRC) clinical trial, and systematic review of the literature. We used multiple evidence sources to separate ED variants into those with strong evidence of pathogenicity and those of uncertain importance. We performed quantitat...
Source: Familial Cancer - May 5, 2021 Category: Cancer & Oncology Source Type: research
Ovarian carcinoma in children with constitutional mutation of SMARCA4 : single-family report and literature review
In this study, we report genetic testing of a family with two children carrying pathogenic germline mutations ofSMARCA4 and summarize the course of SCCOHT in all pediatric patients reported in the literature with constitutional defects identified within theSMARCA4 locus. (Source: Familial Cancer)
Source: Familial Cancer - April 28, 2021 Category: Cancer & Oncology Source Type: research
In memoriam Professor Thierry Fr ébourg
(Source: Familial Cancer)
Source: Familial Cancer - April 28, 2021 Category: Cancer & Oncology Source Type: research
CDH1 pathogenic variants and cancer risk in an unselected patient population
AbstractCDH1 pathogenic variants confer a markedly elevated lifetime risk of developing diffuse gastric cancer (DGC) and lobular breast cancer (LBC). The aim of this study was to evaluate the prevalence and clinical impact ofCDH1 pathogenic variants in the unselected and ancestrally diverse BioMe Biobank. We evaluated exome sequence data from 30,223 adult BioMe participants to identifyCDH1 positive individuals, defined as those harboring a variant previously classified as pathogenic or likely pathogenic or a predicted loss-of-function variant inCDH1. We reviewed electronic health records and BioMe enrollment surveys for pe...
Source: Familial Cancer - April 22, 2021 Category: Cancer & Oncology Source Type: research
Von Hippel-Lindau disease and rapidly progressing pheochromocytomas in siblings
We report a case of two brothers with a strong family history of VHL type 2 due to a pathogenic germline VHL variant, specifically, a surface missense substitution, with a rapidly progressive clinical course that both presented with a large adrenal mass. Both brothers presented with large pheochromocytomas, the earliest presentation being at age 7, despite routine screening. The rapid progression and early presentation of these patients raises an important discussion around the commonly used surveillance protocols for pheochromocytoma in pediatric patients with VHL and missense mutations. We conclude that a more accelerate...
Source: Familial Cancer - April 20, 2021 Category: Cancer & Oncology Source Type: research
Current recommendations for cancer surveillance in Gorlin syndrome: a report from the SIOPE host genome working group (SIOPE HGWG)
This report summarizes genotype-based recommendations for screening patients withPTCH1 andSUFU-related Gorlin syndrome, discussed during a workshop of the Host Genome Working Group of the European branch of the International Society of Pediatric Oncology (SIOPE HGWG) held in January 2020. In order to allow early detection of BCC, dermatologic examination should start at age 10 inPTCH1, and at age 20 inSUFU PV carriers. Odontogenic keratocyst screening, based on odontologic examination, should begin at age 2 with annual orthopantogram beginning around age 8 forPTCH1 PV carriers only. For medulloblastomas, repeated brain MRI...
Source: Familial Cancer - April 16, 2021 Category: Cancer & Oncology Source Type: research
“I wish that there was more info”: characterizing the uncertainty experienced by carriers of pathogenic ATM and/or CHEK2 variants
AbstractLittle is known about what uncertainties patients experience after being identified to carry a pathogenic variant in a moderate-risk cancer gene as a result of undergoing multigene panel testing for cancer susceptibility. Data regarding cancer risk estimates and effectiveness of risk management strategies for these variants continues to evolve, which has the potential to evoke uncertainty. Acknowledging uncertainty during pre- and post-test discussions is imperative to helping individuals to adapt to their results. A better understanding of this population ’s experience of uncertainty is needed to facilitate such...
Source: Familial Cancer - April 15, 2021 Category: Cancer & Oncology Source Type: research
A novel founder MSH2 deletion in Ethiopian Jews is mainly associated with early-onset colorectal cancer
AbstractLynch syndrome is an inherited cancer predisposition syndrome caused by germline defects in any of the mismatch repair (MMR) genes. Diagnosis of carriers makes precision prevention, early detection, and tailored treatment possible. Herein we report a novel founder deletion of 18,758 bp, mediated byAlu repeats on both sides, detected in Ethiopian Jews. The deletion, which encompasses exon 9 –10 of theMSH2 coding sequence, is associated mainly with early-onset MSH2/MSH6-deficient colorectal cancer (CRC) and liposarcoma. Testing of 35 members of 5 seemingly unrelated families of Ethiopian origin yielded 10/21 (48%...
Source: Familial Cancer - April 10, 2021 Category: Cancer & Oncology Source Type: research
Malignancy risk in individuals with familial adenomatous polyposis receiving biologics and immunomodulators
AbstractClinicians may be hesitant to prescribe biologics or immunomodulators to individuals with familial adenomatous polyposis (FAP) and comorbid inflammatory disease (CID) because of increased cancer risk. Our aim was to compare the risk of malignancy in FAP individuals with inflammatory bowel (IBD) and/or rheumatic disease that received biologics/immunomodulators to those who did not. Individuals with FAP and CID were included in the study. We compared the incidence of cancer between individuals exposed to biologics/immunomodulators compared to unexposed from the date of diagnosis of comorbid disease till last follow u...
Source: Familial Cancer - April 6, 2021 Category: Cancer & Oncology Source Type: research
Constitutional 2p16.3 deletion including MSH6 and FBXO11 in a boy with developmental delay and diffuse large B-cell lymphoma
We describe a case of a boy with neurodevelopmental delay and a diffuse large B-cell lymphoma (DLBCL) in whom we discovered a germline de novo 2p16.3 deletion includingMSH6 and part of theFBXO11 gene. A causative role forMSH6 in cancer development was excluded based on tumor characteristics. The constitutionalFBXO11 deletion explains the neurodevelopmental delay in the patient. The FBXO11 protein is involved in BCL-6 ubiquitination and BCL-6 is required for the germinal center reaction resulting in B cell differentiation. Somatic loss of function alterations ofFBXO11 result in BCL-6 overexpression which is a known driver i...
Source: Familial Cancer - April 3, 2021 Category: Cancer & Oncology Source Type: research
Letter to the Editor-Recent advances in Lynch syndrome: response to M øller et al.
(Source: Familial Cancer)
Source: Familial Cancer - April 1, 2021 Category: Cancer & Oncology Source Type: research
Letter to the Editor-Recent advances in Lynch syndrome
(Source: Familial Cancer)
Source: Familial Cancer - April 1, 2021 Category: Cancer & Oncology Source Type: research
Correction to: Letter to the Editor —Recent advances in Lynch syndrome
A correction to this paper has been published: https://doi.org/10.1007/s10689-021-00246-0 (Source: Familial Cancer)
Source: Familial Cancer - April 1, 2021 Category: Cancer & Oncology Source Type: research
Extended gene panel testing in lobular breast cancer
Conclusion: The overall PGV detection rate was 11.59%, with similar rates ofBRCA1/2 (7.28%) PGVs as for other actionable PGVs (7.46%), indicating a benefit for extended panel genetic testing in LBC. We also report a previously unrecognised association of pathogenic variants inATM with LBC. (Source: Familial Cancer)
Source: Familial Cancer - March 25, 2021 Category: Cancer & Oncology Source Type: research
