TP53 variants of uncertain significance: increasing challenges in variant interpretation and genetic counseling
This report cases highlights the challenges and impact ofTP53 variant interpretation especially when there is no clear LFS/LFL phenotype. (Source: Familial Cancer)
Source: Familial Cancer - July 17, 2019 Category: Cancer & Oncology Source Type: research
Lynch syndrome with exclusive skin involvement: time to consider a molecular definition?
AbstractMuir –Torre syndrome (MTS) is clinically characterized by the occurrence of skin, usually sebaceous, and visceral tumors in the same individual. The most common underlying mechanism is a constitutional defect of the mismatch repair (MMR) genes that cause Lynch syndrome (LS). Herewithin we report on a 7 6 years-old male patient heterozygous for a pathogenicMSH2 missense substitution who presented with a striking cutaneous phenotype in the absence of typical LS visceral tumors. The patient developed 20 skin tumors, including sebaceous adenomas/carcinomas and keratoacanthomas. Two skin tumors showed immunohistochem...
Source: Familial Cancer - July 9, 2019 Category: Cancer & Oncology Source Type: research
Hereditary diffuse gastric cancer: cancer risk and the personal cost of preventive surgery
The objective of this research was to examine post-surgical clinical outcomes and to identify which of the domains/symptoms from the European Organisation for Research and Treatment of Cancer QOL Questionnaire (EORTC QLQ-C30) were determinants of overall quality of life (QOL) in individuals undergoing PTG. Participants were recruited through multiple sources. Postsurgical clinical outcomes were obtained from hospital records. Participants completed validated questionnaires measuring generic and condition specific QOL (PROMIS, EORTC and SF 36v.II) at a single point in time. The mean QOL in this cohort was 70.6 (SD = 25...
Source: Familial Cancer - July 3, 2019 Category: Cancer & Oncology Source Type: research
Multiple primary malignancies associated with a germline SMARCB1 pathogenic variant
AbstractA 51-year old presented with a 6-month history of increasing pelvic/lower back pain with nocturnal waking and episodes of anorexia and vomiting. Examination revealed right torticollis and Horner ’s syndrome, and a large abdominal mass arising from the pelvis. Magnetic resonance and positron emission tomography imaging revealed (A) a 14 cm heterogeneous enhancing mass, abutting the left kidney with standardised uptake value max = 2.9, (B) a large heterogeneous enhancing pelvic mass (C ) mesenteric adenopathy standardised uptake value max = 10.3 and (D) 6 cm right lung apex mass standardised uptake value ...
Source: Familial Cancer - June 24, 2019 Category: Cancer & Oncology Source Type: research
Energy balance related lifestyle factors and risk of endometrial and colorectal cancer among individuals with lynch syndrome: a systematic review
AbstractLifestyle factors related to energy balance, such as excess body weight, poor diet, and physical inactivity, are associated with risk of sporadic endometrial cancer (EC) and colorectal cancer (CRC). There are limited data on energy balance-related lifestyle factors and EC or CRC risk among individuals with lynch syndrome, who are at extraordinarily higher risk of developing EC or CRC. We conducted a systematic review of evidence related to weight status, weight change, dietary habits, and physical activity on EC and CRC risk among individuals with lynch syndrome. Findings are reported narratively. We searched Medli...
Source: Familial Cancer - June 23, 2019 Category: Cancer & Oncology Source Type: research
Ability of known susceptibility SNPs to predict colorectal cancer risk for persons with and without a family history
AbstractBefore SNP-based risk can be incorporated in colorectal cancer (CRC) screening, the ability of these SNPs to estimate CRC risk for persons with and without a family history of CRC, and the screening implications need to be determined. We estimated the association with CRC of a 45 SNP-based risk using 1181 cases and 999 controls, and its correlation with CRC risk predicted from detailed family history. We estimated the predicted change in the distribution across predefined risk categories, and implications for recommended screening commencement age, from adding SNP-based risk to family history. The inter-quintile ri...
Source: Familial Cancer - June 16, 2019 Category: Cancer & Oncology Source Type: research
Assessing a single SNP located at TERT/CLPTM1L multi-cancer risk region as a genetic modifier for risk of pancreatic cancer and melanoma in Dutch CDKN2A mutation carriers
AbstractCarriers of pathogenic variants inCDKN2A have a 70% life-time risk of developing melanoma and 15 –20% risk of developing pancreatic cancer (PC). In the Netherlands, a 19-bp deletion in exon 2 ofCDKN2A (p16-Leiden mutation) accounts for most hereditary melanoma cases. Clinical experience suggests variability in occurrence of melanoma and PC inp16-Leiden families. Thereby, the risk of developing cancer could be modified by both environmental and genetic contributors, suggesting that identification of genetic modifiers could improve patients ’ surveillance. In a recent genome-wide association study (GWAS), rs36115...
Source: Familial Cancer - June 14, 2019 Category: Cancer & Oncology Source Type: research
Targeted next generation sequencing screening of Lynch syndrome in Tunisian population
In this study we aimed to identify the underlying genetic cause in 32 patients with early onset CRC and/or a positive family history. Of twenty-four patients ’ tumor or biopsies could be analyzed with immunohistochemical staining to detect loss of expression of one of the MMR proteins. Ten tumors showed loss of expression, of which one tumor was from a patient where a germline pathogenicMSH2 variant was detected previously with Sanger sequencing. Next generation sequencing of the MMR,POLE andPOLD1 genes was performed in leukocyte and tumor DNA of the remaining nine patients, as well as in two patients with MMR-proficient...
Source: Familial Cancer - May 20, 2019 Category: Cancer & Oncology Source Type: research
Endoscopic full thickness resection for early colon cancer in Lynch syndrome
We report a case of a 62 year old man, diagnosed with MSH2-Lynch syndrome, who underwent successful eFTR treatment of an early (pT1) colon cancer located in the ascending colon, with no signs of recurrence 12 months after treatment. We discuss the pros and cons of endoscopic re section of early colorectal carcinoma in Lynch syndrome patients. (Source: Familial Cancer)
Source: Familial Cancer - May 19, 2019 Category: Cancer & Oncology Source Type: research
The incidence of consecutive manifestations in Von Hippel-Lindau disease
In this study we aimed to gain insight into the development of subsequent manifestations in VHL disease. We retrospectively scored each new VHL-related manifestation as detected by standard follow-up (retina, central nervous system, kidneys and pancreas, excluding adrenal and endolymfatic sac manifestations) in 75VHL mutation carriers. The Kaplan –Meier method was used to plot the cumulative proportions of all consecutive manifestations in each organ against age. The cumulative average number of manifestations in all organs during life was calculated by summating these cumulative proportions. Poisson model parameters wer...
Source: Familial Cancer - May 12, 2019 Category: Cancer & Oncology Source Type: research
Genetic counseling referral for ovarian cancer patients: a call to action
The objective of the study was to determine if disparities exist in genetic referrals and characterize referral patterns over time. A retrospective cohort study included all women diagnosed with invasive epithelial ovarian cancer at the University of Virginia from 2004 to 2015. Clinicopathologic data were abstracted from the electronic medical record and analyzed for association with genetic referral and testing. We identified 696 cases, with a median age of 62 years and a median follow up of 25.2 months (range 1–115). Thirty-four percent were referred for genetic counseling with an 80% genetic testing rate in those w...
Source: Familial Cancer - April 15, 2019 Category: Cancer & Oncology Source Type: research
Implication of DNA repair genes in Lynch-like syndrome
AbstractMany colorectal cancers (CRCs) that exhibit microsatellite instability (MSI) are not explained byMLH1 promoter methylation or germline mutations in mismatch repair (MMR) genes, which cause Lynch syndrome (LS). Instead, these Lynch-like syndrome (LLS) patients have somatic mutations in MMR genes. However, many of these patients are young and have relatives with cancer, suggesting a hereditary entity. We performed germline sequence analysis in LLS patients and determined their tumor ’s mutational profiles using FFPE DNA. Six hundred and fifty-four consecutive CRC patients were screened for suspected LS using MSI an...
Source: Familial Cancer - April 14, 2019 Category: Cancer & Oncology Source Type: research
Hereditary gastric cancer: what ’s new? Update 2013–2018
AbstractAround 10 –20% of gastric cancer patients have relatives with a diagnosis of GC and in 1–3% of patients a genetic cause can be confirmed. Histopathologically, GC is classified into intestinal-type, with glandular growth, and diffuse-type with poorly cohesive growth pattern often with signet ring cells. Fa milial or hereditary GC is classified into hereditary diffuse GC (HDGC), familial intestinal GC (FIGC) and polyposis forms. This review focuses on recent research findings and new concepts of hereditary GC. (Source: Familial Cancer)
Source: Familial Cancer - April 14, 2019 Category: Cancer & Oncology Source Type: research
Development and pilot testing of a leaflet informing women with breast cancer about genomic testing for polygenic risk
This study aimed to develop, and pilot test a leaflet with a sample of women participating in a large prospective cohort study. The leaflet aimed to provide information about polygenic risk to assist women to decide whether or not to learn results from genomic testing for common risk variants associated with breast cancer risk. A prototype of the leaflet was developed based on published literature and with the expertise from a multidisciplinary team. The acceptability of the leaflet was assessed by self-report questionnaire among 29 women participating in the prospective cohort study. More than 80% participants stated that...
Source: Familial Cancer - March 31, 2019 Category: Cancer & Oncology Source Type: research
Referral frequency, attrition rate, and outcomes of germline testing in patients with pancreatic adenocarcinoma
AbstractHereditary predisposition is estimated to account for 10% of all pancreatic cancer cases. However, referral patterns and clinical workflow for germline testing in this disease differ significantly by institution, and many at-risk patients may not undergo appropriate counseling and testing. We undertook an analysis of patients diagnosed with pancreatic cancer (PDAC) who were referred to the Clinical Genetics program of a high-volume academic center over a 3-year period to assess referral frequency, evaluate the yield of germline testing in this selected patient cohort, and elucidate the reasons individuals did not u...
Source: Familial Cancer - March 31, 2019 Category: Cancer & Oncology Source Type: research
