Exploring the preferences of involved health professionals regarding the implementation of an online decision aid to support couples during reproductive decision-making in hereditary cancer: a mixed methods approach
AbstractTo support persons having a genetic predisposition to cancer and their partners during reproductive decision-making, an online decision aid was developed and evaluated. To maximize the impact of the support tool, this mixed methods study aims at developing the optimal implementation strategy for the decision aid. A questionnaire to assess the critical determinants that may affect this implementation was completed by health professionals involved in oncogenetic counselling (N  = 46). Subsequently, semi-structured focus groups (N = 19) and individual telephonic interviews (N =&thins...
Source: Familial Cancer - January 17, 2019 Category: Cancer & Oncology Source Type: research

Recent advances in Lynch syndrome
AbstractLynch syndrome is one of the most common hereditary cancer predisposition syndromes and is associated with increased risks of colorectal and endometrial cancer, as well as multiple other cancer types. While the mechanism of mismatch repair deficiency and microsatellite instability and its role in Lynch-associated carcinogenesis has been known for some time, there have been significant advances recently in diagnostic testing and the understanding of the molecular pathogenesis of Lynch tumors. There is also an increased awareness that the clinical phenotype and cancer risk varies by specific mismatch repair mutation,...
Source: Familial Cancer - January 9, 2019 Category: Cancer & Oncology Source Type: research

TP53 germline mutation testing in early-onset breast cancer: findings from a nationwide cohort
AbstractEarly-onset breast cancer may be due to Li –Fraumeni Syndrome (LFS). Current national and international guidelines recommend thatTP53 genetic testing should be considered for women with breast cancer diagnosed before the age of 31  years. However, large studies investigatingTP53 mutation prevalence in this population are scarce. We collected nationwide laboratory records for all young breast cancer patients tested forTP53 mutations in the Netherlands. Between 2005 and 2016, 370 women diagnosed with breast cancer younger than 30  years of age were tested forTP53 germline mutations, and eight (2.2%) w...
Source: Familial Cancer - January 3, 2019 Category: Cancer & Oncology Source Type: research

Multi-gene panel testing confirms phenotypic variability in MUTYH -Associated Polyposis
We report the phenotypic spectrum of MAP in the context of multi-gene hereditary cancer panel testing. Genetic testing results and clinical histories were reviewed for individuals with biallelicMUTYH PVs detected by panel testing at a single commercial molecular diagnostic laboratory. BiallelicMUTYH PVs were identified in 82 individuals (representing 0.2% of tested individuals) with most (75/82; 91.5%) reporting a personal history of CRC and/or polyps. Ten percent (6/61) of individuals reporting polyp number reported fewer than 10 polyps and therefore did not meet current MAP testing criteria. Extracolonic cancers (21/82; ...
Source: Familial Cancer - January 2, 2019 Category: Cancer & Oncology Source Type: research

Low-level parental mosaicism in an apparent de novo case of Peutz –Jeghers syndrome
We report the case of a female found to have mosaicism for mutation in theSTK11 gene, with the mutant allele expressed in her gametes, evident by her affected offspring, and in her gastrointestinal tract demonstrated on an excised polyp analysed for diagnosis. Mosaicism for Peutz –Jeghers syndrome (PJS) has been reported in a small number of cases previously but a clinical presentation such as this has not previously been described. This finding of mosaicism was several years after initial investigations failed to identify the sameSTK11 mutation in this woman whose son was diagnosed with PJS at a young age. This case...
Source: Familial Cancer - January 1, 2019 Category: Cancer & Oncology Source Type: research

Capillary electrophoresis as alternative method to detect tumor genetic mutations: the model built on the founder BRCA1 c.4964_4982del19 variant
In this study, we developed a rapid and reliable PCR method, coupled with capillary electrophoresis (CE) for genotyping the Italian founderBRCA1 c.4964_4982del19 (rs80359876) variant. In addition, we compared the performance of two CE platforms: (Agilent 2100 Bioanalyzer and the Experion Automated Electrophoresis system) to identify this variant. Our findings suggest that CE represents a simple and standardized diagnostic strategy for the unambiguously identification of theBRCA1 c.4964_4982del19 variant, on both germline and somatic DNA samples. The results and performance obtained by two platforms are absolutely superimpo...
Source: Familial Cancer - January 1, 2019 Category: Cancer & Oncology Source Type: research

Monoallelic MUTYH carrier status is not associated with increased breast cancer risk in a multigene panel cohort
This study aimed to determine if monoallelicMUTYH mutations are associated with increased breast cancer risk in women undergoing multigene panel testing (MGPT). The prevalence of monoallelicMUTYH mutations was compared between Non-Hispanic white female breast cancer cases (n  = 30,456) and cancer-free controls (n = 12,289), all of whom underwent MGPT that includedMUTYH. We tested breast cancer associations withMUTYH alleles using Fisher ’s exact test, followed by multivariate logistic regression adjusted for age at testing and MGPT type ordered. Frequencies of the two most commonMUTYH foun...
Source: Familial Cancer - December 23, 2018 Category: Cancer & Oncology Source Type: research

A squamous cell carcinoma in a young woman with Lynch syndrome
AbstractLynch syndrome (LS) is an autosomal-dominant inherited disorder characterized by a predisposition to colorectal cancer and extracolonic cancers (particularly endometrium, ovary, stomach, small bowel, hepatobiliary tract, pancreas, urothelial tract, brain, and skin). Muir –Torre syndrome (MTS) is considered a phenotypical variant of LS, where patients develop sebaceous neoplasms and keratoacanthomas. Currently, only few studies and case reports suggest an association between LS and other skin cancers, such as Bowens’ disease, melanoma and squamous cell carcinoma (SCC). In this case-report we describe the...
Source: Familial Cancer - December 17, 2018 Category: Cancer & Oncology Source Type: research

Hereditary brain tumor with a homozygous germline mutation in PMS2 : pedigree analysis and prenatal screening in a family with constitutional mismatch repair deficiency (CMMRD) syndrome
AbstractPrecise genetic counseling and prenatal diagnosis are often hindered by incomplete penetrance of risk variance and complex patterns of inheritance. Here, we performed a clinical and genetic study of a five-generation Pakistani family with a history of multiple cases of childhood brain tumors. Six affected individuals died of brain tumors at very early ages and three were confirmed as having a homozygous mutation in exon 6 of thePMS2 gene (c.543delT). Fifteen members of the family were identified as heterozygous carriers of this mutation with a lack of cancer incidence. Both clinical manifestations and genetic test ...
Source: Familial Cancer - November 26, 2018 Category: Cancer & Oncology Source Type: research

Germline mutation p.N363K in POLE is associated with an increased risk of colorectal cancer and giant cell glioblastoma
We report a family with an autosomal dominant inheritance of PPAP due to a c.1089C>A; p.Asn363Lys mutation in the proofreading exonuclease domain ofPOLE. Ten patients presenting a history of colorectal tumours and three patients with polyposis are indexed in this family. Three carriers (including siblings and a distant cousin at 30, 45 and 52 respectively) and another member (at 37 not tested) presented glioblastoma. This is the second family reported to carry this mutation. Among the four glioblastomas in the family that we report, both show similar pathology: giant cell glioblastoma. These cases suggest that the c.108...
Source: Familial Cancer - October 27, 2018 Category: Cancer & Oncology Source Type: research

Cleft lip/palate and hereditary diffuse gastric cancer: report of a family harboring a CDH1 c.687  + 1G  & gt;  A germline mutation and review of the literature
This study highlights that CLP represents an important phenotypic feature ofCDH1 germline mutation carriers and emphasizes the inclusion of CLP in the HDGC testing criteria. The underlying causes for the appearance of variable phenotypes inCDH1 mutation carriers could include genetic variation, epigenetic changes and environmental factors and should be investigated in future studies. (Source: Familial Cancer)
Source: Familial Cancer - October 10, 2018 Category: Cancer & Oncology Source Type: research

Risk of multiple colorectal cancer development depends on age and subgroup in individuals with hereditary predisposition
AbstractDevelopment of multiple colorectal cancers (CRCs), synchronously or metachronously, is associated with hereditary predisposition for cancer and accurate risk estimates of multiple tumour development are relevant to recommend rational surveillance programs. A cross-sectional study design was used to estimate the risks of synchronous CRC (SCRC) and metachronous CRC (MCRC) based on data from the National Danish Hereditary Nonpolyposis Register. In total, 7100 individuals from families within the subgroups Lynch syndrome, familial CRC (FCC) and moderate risk were used with estimates relative to a non-hereditary populat...
Source: Familial Cancer - October 9, 2018 Category: Cancer & Oncology Source Type: research

Boosting care and knowledge about hereditary cancer: European Reference Network on Genetic Tumour Risk Syndromes
AbstractApproximately 27 –36 million patients in Europe have one of the ~ 5.000–8.000 known rare diseases. These patients often do not receive the care they need or they have a substantial delay from diagnosis to treatment. In March 2017, twenty-four European Reference Networks (ERNs) were launched with the aim to im prove the care for these patients through cross border healthcare, in a way that the medical knowledge and expertise travels across the borders, rather than the patients. It is expected that through the ERNs, European patients with a rare disease get access to expert care more often and...
Source: Familial Cancer - October 9, 2018 Category: Cancer & Oncology Source Type: research

Ovarian small cell carcinoma in one of a  pair of monozygous twins
AbstractOne of a pair of monozygous twins was diagnosed and died of small cell carcinoma of the ovary of hypercalcemic type (SCCOHT) at the age of 30  years. Her sister remained unaffected and was very concerned about her risk for developing SCCOHT. By performing comprehensive molecular analysis using whole exome sequencing (WES) approach, we showed that the deceased twin’s tumour has bi-allelic somatic genetic defects (a pathogenic frameshift deletion inSMARCA4 and LOH on chr19p). Results of WES of constitutional DNA from her unaffected sister were confirmatory. Based on our findings, we concluded that the livi...
Source: Familial Cancer - October 4, 2018 Category: Cancer & Oncology Source Type: research

Molecular analysis of an asbestos-exposed Belgian family with a high prevalence of mesothelioma
In this study, we report a previously undescribed Belgian family, in which BAP1 was found to be absent in the epithelial malignant mesothelial cells of the index patient. Whole exome analysis did not reveal a germline or somaticBAP1 variant. Also, no germline or somatic copy number changes in theBAP1 region could be identified. However, germline variants, predicted to be damaging, were detected in 11 other ‘Cancer census genes’ (i.e.MPL, RBM15, TET2, FAT1, HLA-A, EGFR, KMT2C, BRD3, NOTCH1, RB1 andMYO5A). Of these, the one inRBM15 seems to be the most interesting given its low minor allele frequency and absence ...
Source: Familial Cancer - October 1, 2018 Category: Cancer & Oncology Source Type: research

Clinical interpretation of pathogenic ATM and CHEK2 variants on multigene panel tests: navigating moderate risk
AbstractComprehensive genomic cancer risk assessment (GCRA) helps patients, family members, and providers make informed choices about cancer screening, surgical and chemotherapeutic risk reduction, and genetically targeted cancer therapies. The increasing availability of multigene panel tests for clinical applications allows testing of well-defined high-risk genes, as well as moderate-risk genes, for which the penetrance and spectrum of cancer risk are less well characterized. Moderate-risk genes are defined as genes that, when altered by a pathogenic variant, confer a 2 to fivefold relative risk of cancer. Two such genes ...
Source: Familial Cancer - October 1, 2018 Category: Cancer & Oncology Source Type: research

Gene expression analysis in peripheral blood cells of patients with hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC): identification of NRF2 pathway activation
AbstractHereditary leiomyomatosis and renal cell cancer syndrome (HLRCC) is a very rare disease that is inherited in an autosomal dominant manner. Affected patients may develop from cutaneous and uterine leiomyomas to type 2 papillary renal cell carcinoma (Schmidt and Linehan, Int J Nephrol Renovasc Dis 7:253 –260, 2014). HLRCC is caused by germline mutations in theFH gene, which produces the fumarate hydratase protein that participates in the tricarboxylic acid cycle during the conversion of fumarate to malate. InFH-deficient cells, high concentrations of fumarate lead to a series of intricate events, which seem to ...
Source: Familial Cancer - October 1, 2018 Category: Cancer & Oncology Source Type: research

Discussions about predictive genetic testing for Lynch syndrome: the role of health professionals and families in decisions to decline
AbstractUnaffected relatives of individuals with Lynch syndrome can be offered predictive genetic testing to guide surveillance recommendations. The decision-making process of those who decline testing, particularly those who do not attend a clinical genetics service, is poorly understood. We have addressed this gap by interviewing 33 individuals from Lynch syndrome mutation-carrying families, unaffected by cancer, who declined predictive genetic testing. Here, we analyse the data provided by 20 participants who unequivocally declined testing. Those who indicated they did not have enough information to make a decision or i...
Source: Familial Cancer - October 1, 2018 Category: Cancer & Oncology Source Type: research

Urological sequelae of desmoids associated with familial adenomatous polyposis
AbstractThe aim of this retrospective cohort study was to review urological complication rates arising from familial adenomatous polyposis associated desmoid tumours and their management. All patients over a 35-year period were identified from a prospectively maintained polyposis registry database and had an intra-abdominal desmoid tumour. Those without ureteric complications (n  = 118, group A) were compared to those that developed ureteric obstruction (n = 40, group B) for demographics, treatment interventions and survival outcomes. 158 (56% female) patients were identified. Median age at diag...
Source: Familial Cancer - October 1, 2018 Category: Cancer & Oncology Source Type: research

APC mosaicism in a young woman with desmoid type fibromatosis and familial adenomatous polyposis
AbstractFamilial adenomatous polyposis (FAP) is usually caused by germline mutations in the adenomatous polyposis coli (APC) gene. The classic form is characterized by hundreds to thousands of adenomas in the colorectum and early onset colorectal cancer (CRC) if left untreated. FAP is also associated with multiple extra-colonic manifestations such as gastroduodenal polyps, osteomas, epidermoid cysts, fibromas and desmoids. Most desmoid tumours in FAP patients occur intra-abdominally. Approximately 15 –20% of theAPC mutations are de novo mutations. Somatic mosaicism has been reported in some sporadic cases of polyposi...
Source: Familial Cancer - October 1, 2018 Category: Cancer & Oncology Source Type: research

SNP association study in PMS2-associated Lynch syndrome
AbstractLynch syndrome (LS) patients are at high risk of developing colorectal cancer (CRC). Phenotypic variability might in part be explained by common susceptibility loci identified in Genome Wide Association Studies (GWAS). Previous studies focused mostly onMLH1, MSH2 andMSH6 carriers, with conflicting results. We aimed to determine the role of GWAS SNPs inPMS2 mutation carriers. A cohort study was performed in 507PMS2 carriers (124 CRC cases), genotyped for 24 GWAS SNPs, including SNPs at 11q23.1 and 8q23.3. Hazard ratios (HRs) were calculated using a weighted Cox regression analysis to correct for ascertainment bias. ...
Source: Familial Cancer - October 1, 2018 Category: Cancer & Oncology Source Type: research

Feasibility of endoscopic resection using bipolar snare for nonampullary duodenal tumours in familial adenomatous polyposis patients
AbstractThe management of duodenal and colorectal tumours is important in patients with familial adenomatous polyposis (FAP). Endoscopic resection (ER) should be carefully performed because the risk of complications during or after (ER) of nonampullary duodenal tumours is higher than that of stomach or colorectal lesions in general. Thus, we evaluated the feasibility of endoscopic resection using bipolar snare (ERB) for nonampullary duodenal tumours in FAP patients. Eleven FAP patients who underwent ERB for nonampullary duodenal tumours at our hospital between October 2013 and December 2016 were retrospectively analysed ba...
Source: Familial Cancer - October 1, 2018 Category: Cancer & Oncology Source Type: research

Risk management adherence following genetic testing for hereditary cancer syndromes: a Singaporean experience
AbstractAssessing adherence behavior among mutation carriers to cancer risk management guidelines is important for both service improvement and cost-effectiveness analyses, but such real-world data is often lacking. The present study aims to report adherence rates among mutation carriers in a recently established cancer genetics program in Singapore. We conducted a medical chart review of mutation carriers who had attended for genetic counseling and gathered data regarding risk management behavior, including cancer surveillance and/or risk-reducing surgery, and cancers subsequently detected. Of the 52 subjects included in ...
Source: Familial Cancer - October 1, 2018 Category: Cancer & Oncology Source Type: research

Adaptation of couples living with a high risk of breast/ovarian cancer and the association with risk-reducing surgery
AbstractWomen who carryBRCA1/2 mutations have a significantly elevated risk for breast and ovarian cancer. The positive test result and subsequent decisions about risk reducing behaviors can evoke distress, anxiety and worry. Psychological adaptation, or the process of coming to terms with the implications of a health threat, is an understudied construct inBRCA1/2 carriers. Little is known about adaptation and how it relates to other aspects of living at high risk for cancer. Even less is understood about adaptation among partners ofBRCA1/2 carriers, and its relationship to adaptation in high risk individuals. Women at inc...
Source: Familial Cancer - October 1, 2018 Category: Cancer & Oncology Source Type: research

Correlation of IL-31 gene polymorphisms with susceptibility and clinical recurrence of bladder cancer
AbstractInterleukin-31 is a crucial cytokine triggering inflammation which could be one of the risk factors of tumors. However, data for correlation betweenIL-31 and tumors are limited. The purpose of our study was to discuss whether genetic polymorphisms ofIL-31 were associated with the susceptibility and clinical outcomes of bladder cancer. Our study enrolled 478 controls, 156 non-muscle-invasive bladder cancer (NMIBC) and 138 muscle-invasive bladder cancer (MIBC) patients. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for genotyping two single nucleotide polymorphisms (SNP...
Source: Familial Cancer - October 1, 2018 Category: Cancer & Oncology Source Type: research

Molecular analysis of an asbestos-exposed Belgian family with a high prevalence of mesothelioma
In this study, we report a previously undescribed Belgian family, in which BAP1 was found to be absent in the epithelial malignant mesothelial cells of the index patient. Whole exome analysis did not reveal a germline or somaticBAP1 variant. Also, no germline or somatic copy number changes in theBAP1 region could be identified. However, germline variants, predicted to be damaging, were detected in 11 other ‘Cancer census genes’ (i.e.MPL, RBM15, TET2, FAT1, HLA-A, EGFR, KMT2C, BRD3, NOTCH1, RB1 andMYO5A). Of these, the one inRBM15 seems to be the most interesting given its low minor allele frequency and absence ...
Source: Familial Cancer - October 1, 2018 Category: Cancer & Oncology Source Type: research

A retrospective review of 48 individuals, including 12 families, molecularly diagnosed with hereditary leiomyomatosis and renal cell cancer (HLRCC)
AbstractHereditary leiomyomatosis and renal cell cancer (HLRCC) is caused by autosomal dominant germline mutations in the fumarate hydratase (FH) gene and is characterized by cutaneous leiomyomas, uterine leiomyomas and aggressive renal malignancies. We conducted a retrospective chart review to characterize the patients referred to our Regional Genetics Program for assessment of HLRCC from 2004 to mid-2016. Forty-eight of 69 (69.5%) referred individuals were positive for a pathogenic or likely pathogenic variant inFH; they had an average age of 39.1  years. There were 11 differentFH variants among them. As expected, t...
Source: Familial Cancer - October 1, 2018 Category: Cancer & Oncology Source Type: research

Mutations in SUFU and PTCH1 genes may cause different cutaneous cancer predisposition syndromes: similar, but not the same
AbstractMany cancer predisposition syndromes are preceded or accompanied by a range of typical skin signs. Gorlin syndrome is a rare multisystem inherited disorder which can predispose to basal cell carcinomas (BCCs), childhood medulloblastomas in addition to various developmental abnormalities; the majority of cases are due to mutations in thePTCH1 gene. Approximately 5% of cases have been attributed to a mutation in theSUFU gene. Certain phenotypic features have been identified as being more prevalent in individuals with aSUFU mutation such as childhood medulloblastoma, infundibulocystic BCCs and trichoepitheliomas. Rece...
Source: Familial Cancer - October 1, 2018 Category: Cancer & Oncology Source Type: research

Haplotype analysis suggest that the MLH1 c.2059C   & gt;  T mutation is a Swedish founder mutation
AbstractLynch syndrome (LS) predisposes to a spectrum of cancers and increases the lifetime risk of developing colorectal- or endometrial cancer to over 50%. Lynch syndrome is dominantly inherited and is caused by defects in DNA mismatch-repair genesMLH1, MSH2, MSH6 orPMS2, with the vast majority detected inMLH1 andMSH2. Recurrent LS-associated variants observed in apparently unrelated individuals, have either arisen de novo in different families due to mutation hotspots, or are inherited from a founder (a common ancestor) that lived several generations back. There are variants that recur in some populations while also act...
Source: Familial Cancer - October 1, 2018 Category: Cancer & Oncology Source Type: research

Metachronous colorectal cancer following segmental or extended colectomy in Lynch syndrome: a systematic review and meta-analysis
AbstractAround 5% of colorectal cancers are due to mutations within DNA mismatch repair genes, resulting in Lynch syndrome (LS). These mutations have a high penetrance with early onset of colorectal cancer at a mean age of 45  years. The mainstay of surgical management is either a segmental or extensive colectomy. Currently there is no unified agreement as to which management strategy is superior due to limited conclusive empirical evidence available. A systematic review and meta- analysis to evaluate the risk of metach ronous colorectal cancer (MCC) and mortality in LS following segmental and extensive colectomy. A s...
Source: Familial Cancer - October 1, 2018 Category: Cancer & Oncology Source Type: research

The first two confirmed sub-Saharan African families with germline TP53 mutations causing Li-Fraumeni syndrome
This study reports the first cases of molecularly confirmed LFS germline mutations in sub-Saharan Africa. Three black African patients, all with LFS-associated cancers, were seen through the Clinical and Counselling Section of the Division of Human Genetics at the National Health Laboratory Service and University of the Witwatersrand in Johannesburg, South Africa, during 2011 –2012. All three patients (two were related) were recruited into this research study. Sequence analysis of the coding region of theTP53 gene identified a Class IV (likely pathogenic) variant, c.326T  >  C (p.Phe109Ser), in the t...
Source: Familial Cancer - October 1, 2018 Category: Cancer & Oncology Source Type: research

Response to letter to editor regarding published article —metachronous colorectal cancer following segmental or extended colectomy in Lynch syndrome: a systematic review and meta-analysis
(Source: Familial Cancer)
Source: Familial Cancer - October 1, 2018 Category: Cancer & Oncology Source Type: research

Commentary:  PREMM5 threshold of 2.5% is recommended to improve identification of PMS2 carriers
(Source: Familial Cancer)
Source: Familial Cancer - October 1, 2018 Category: Cancer & Oncology Source Type: research

Letter to the editor
(Source: Familial Cancer)
Source: Familial Cancer - October 1, 2018 Category: Cancer & Oncology Source Type: research

Genetic counselling of young women with breast cancer for Li –Fraumeni syndrome: a nationwide survey on the experiences and attitudes of genetics professionals
This study aims to gain more knowledge on the attitudes and experiences among genetics professionals regarding the timing and content of genetic counselling of young breast cancer patients for Li –Fraumeni syndrome (LFS). We conducted a nationwide online survey among genetics professionals who provide cancer genetic counselling in the Netherlands. Fifty-seven professionals completed the questionnaire (response rate overall 54%, clinical geneticists 70%). Most respondents reported that they discuss the option ofTP53 genetic testing —simultaneously withBRCA 1/2—during the initial counselling visit, especial...
Source: Familial Cancer - September 20, 2018 Category: Cancer & Oncology Source Type: research

Interest in, willingness-to-pay for and willingness-to-recommend genetic testing for prostate cancer among affected men after radical prostatectomy
This study aimed to gain insight into men ’s attitudes in genetic testing for PCa. 4699 men with PCa from the German multicenter prospective database “Familial Prostate Cancer” were included. Interest in, Willingness-to-pay for and Willingness-to-recommend a genetic test for PCa were quantified. Associations with several sociodemograp hic and psychosocial variables were evaluated by logistic regression. 76.8% of the affected men with a median follow-up of 12.9 years were interested in a genetic test for PCa. Newly identified variables significantly associated with interest were having sons (OR 1.66, p 
Source: Familial Cancer - September 18, 2018 Category: Cancer & Oncology Source Type: research

Massive juvenile polyposis of the stomach in a family with SMAD4 gene mutation
We describe a family in which the proband (a 46-year old woman) had massive polyposis of the stomach —leading to surgery—with high-grade dysplasia at histology. Molecular analysis was carried out using Next Generation sequencing techniques with Miseq Illumina Platforms and a minimal coverage of 40 reads. In the proband, the analysis showed the presence of a truncating mutation in theSMAD4 gene (c.1213dupC, a variant previously associated with juvenile polyposis and Hereditary Hemorrhagic Teleangectasia). The same mutation was detected in two other members of the family (father and brother of the proband), who s...
Source: Familial Cancer - September 8, 2018 Category: Cancer & Oncology Source Type: research

The BRCA1 exon 13 duplication: clinical characteristics of 22 families in Northern Sweden
AbstractThe clinical management ofBRCA1/2 mutation carriers requires accurate cancer risk estimates. Cancer risks vary according to type and location of the mutation and since there is limited information about mutation-specific cancer risks, genotype-phenotype correlation studies are needed. This is a report of 22 families with the same mutation,BRCA1 duplication exon 13, a mutation that is found world-wide, with the objective to describe the cancer history found in these families. We studied 69 confirmed carriers, 53 women and 16 men, and additionally 29 women who were clinically expected carriers. Among the confirmed ca...
Source: Familial Cancer - August 22, 2018 Category: Cancer & Oncology Source Type: research

Candidate susceptibility variants in angioimmunoblastic T-cell lymphoma
AbstractAngioimmunoblastic T-cell lymphoma (AITL) is a subtype of peripheral T-cell lymphoma with a poor prognosis: the 5-year survival rate is approximately 30%. Somatic driver mutations have been found inTET2, IDH2, DNMT3A, RHOA, FYN, PLCG1, andCD28, whereas germline susceptibility to AITL has to our knowledge not been studied. The homogenous Finnish population is well suited for studies on genetic predisposition. Here, we performed an exome-wide rare variant analysis in 23 AITL patients. No germline mutations were found in the driver genes, implying that they are not frequently involved in genetic AITL predisposition. P...
Source: Familial Cancer - August 10, 2018 Category: Cancer & Oncology Source Type: research

Modified capture –recapture estimates of the number of families with Lynch syndrome in Central Ohio
In this study we modified the capture –recapture method from ecology to estimate the number of families in central Ohio with Lynch syndrome (LS). We screened 1566 colorectal cancer cases and 545 endometrial cancer cases in central Ohio from 1999 to 2005 and identified 58 with LS. We screened an additional 3346 colorectal and 342 endom etrial cancer cases from 2013 to 2016 and identified 149 with LS. We found 12 LS mutations shared between families observed in the first and second studies. We identified three individuals between studies who were closely related and eight who were more distantly related. We used identi...
Source: Familial Cancer - July 17, 2018 Category: Cancer & Oncology Source Type: research

Outcome of thyroid ultrasound screening in FAP patients with a normal baseline exam
AbstractFamilial adenomatous polyposis (FAP) is a hereditary cancer syndrome associated with a substantial lifetime risk for colorectal cancer. The leading extra-colonic causes of cancer in FAP include duodenal and thyroid cancer (TC). Recent guidelines recommend annual thyroid ultrasound (TUS) screening beginning in the teenage years but the evidence to support the interval particularly in FAP patients with a normal baseline ultrasound is lacking. TUS results from FAP patients enrolled in a thyroid screening program from 2006 to 2016 and who had at least 2 TUS were reviewed. TUS findings were classified as normal, low (LR...
Source: Familial Cancer - July 12, 2018 Category: Cancer & Oncology Source Type: research

Evaluation of an online family history tool for identifying hereditary and familial colorectal cancer
AbstractIdentifying a hereditary colorectal cancer (CRC) syndrome or familial CRC (FCC) in a CRC patient may enable the patient and relatives to enroll in surveillance protocols. As these individuals are insufficiently recognized, we evaluated an online family history tool, consisting of a patient-administered family history questionnaire and an automated genetic referral recommendation, to facilitate the identification of patients with hereditary CRC or FCC. Between 2015 and 2016, all newly diagnosed CRC patients in five Dutch outpatient clinics, were included in a trial with a stepped-wedge design, when first visiting th...
Source: Familial Cancer - June 13, 2018 Category: Cancer & Oncology Source Type: research

Screening for germline mutations in mismatch repair genes in patients with Lynch syndrome by next generation sequencing
AbstractLynch syndrome (LS) is an autosomal dominant disorder, with high penetrance that affects approximately 3% of the cases of colorectal cancer. Affected individuals inherit germline mutations in genes responsible for DNA mismatch repair, mainly atMSH2, MLH1, MSH6 andPMS2. The molecular screening of these individuals is frequently costly and time consuming due to the large size of these genes. In addition,PMS2 mutation detection is often a challenge because there are 16 different pseudogenes identified until now. In the present work we evaluate a molecular screening strategy based in next generation sequencing (NGS) in...
Source: Familial Cancer - June 13, 2018 Category: Cancer & Oncology Source Type: research

Ectopic, retroperitoneal adrenocortical carcinoma in the setting of Lynch syndrome
We present the case of a 68-year-old male with a confirmed diagnosis of Lynch syndrome secondary to a germlineMSH2 mismatch-repair gene-mutation who presented with 2  months history of non-specific abdominal pain. After imaging work-up, the patient was found to have a right upper quadrant, retroperitoneal mass. Biochemical tests were without any evidence of a hormonally active process. Fine needle aspiration of the mass revealed a poorly differentiated carcinom a of unknown etiology. The lesion was resected and found to be consistent with ectopic ACC with an associatedMSH2 mutation. (Source: Familial Cancer)
Source: Familial Cancer - June 13, 2018 Category: Cancer & Oncology Source Type: research

Evaluation of current prediction models for Lynch syndrome: updating the PREMM5 model to identify PMS2 mutation carriers
AbstractUntil recently, no prediction models for Lynch syndrome (LS) had been validated forPMS2 mutation carriers. We aimed to evaluate MMRpredict and PREMM5 in a clinical cohort and forPMS2 mutation carriers specifically. In a retrospective, clinic-based cohort we calculated predictions for LS according to MMRpredict and PREMM5. The area under the operator receiving characteristic curve (AUC) was compared between MMRpredict and PREMM5 for LS patients in general and for different LS genes specifically. Of 734 index patients, 83 (11%) were diagnosed with LS; 23MLH1, 17MSH2, 31MSH6 and 12PMS2 mutation carriers. Both predicti...
Source: Familial Cancer - June 13, 2018 Category: Cancer & Oncology Source Type: research

Cholesterol profile in women with premature menopause after risk reducing salpingo-oophorectomy
AbstractThis cross-sectional study aimed to investigate the effect of premenopausal risk reducing salpingo-oophorectomy (RRSO) on the cholesterol profile of women at increased ovarian cancer risk and to assess possible effects of age at and time since RRSO. We included 207 women who underwent RRSO before menopausal age (52  years) attending the family cancer clinic of an academic hospital and 828 age-matched women from a general population cohort (PREVEND). Participants filled out a questionnaire on socio-demographic characteristics, lifestyle and medical history, had anthropometric measurements and provided blood sa ...
Source: Familial Cancer - June 7, 2018 Category: Cancer & Oncology Source Type: research

The uptake of presymptomatic genetic testing in hereditary breast-ovarian cancer and Lynch syndrome: a systematic review of the literature and implications for clinical practice
AbstractFollowing the identification in a proband of a germlineBRCA1/BRCA2 mutation in hereditary breast-ovarian cancer (HBOC) or a DNA mismatch repair gene mutation in Lynch syndrome (LS) he or she will be asked to inform at-risk family members about the option for presymptomatic DNA testing. However, in clinical practice multiple factors may complicate the process of information sharing. We critically evaluated studies on the uptake of presymptomatic genetic testing in both syndromes. A search of relevant MeSH terms and key words in PubMed, Embase and PsycINFO yielded 795 articles published between 2001 and 2017. Thirty ...
Source: Familial Cancer - May 30, 2018 Category: Cancer & Oncology Source Type: research

The development of an online decision aid to support persons having a genetic predisposition to cancer and their partners during reproductive decision-making: a usability and pilot study
AbstractAn online decision aid to support persons having a genetic predisposition to cancer and their partners during reproductive decision-making was developed. A two-phase usability test was conducted among 12 couples (N  = 22; 2 persons participated without their partner) at risk for hereditary cancer and 15 health care providers. Couples and health care providers expressed similar suggestions for improvements, and evaluated the modified decision aid as acceptable, easy to use, and comprehensible. The final dec ision aid was pilot tested (N = 16) with paired sample t tests comparing main outc...
Source: Familial Cancer - May 30, 2018 Category: Cancer & Oncology Source Type: research

Identification of a novel GREM1 duplication in a patient with multiple colon polyps
AbstractHereditary mixed polyposis syndrome (HMPS) is a hereditary syndrome that is characterized by multiple colon polyps of mixed pathologic subtypes and an increased risk for colorectal cancer. A 40  kb duplication in the 5′ regulatory region of theGREM1 gene was recently found to be the causal mutation in a subset of Ashkenazi Jewish families with HMPS. Given this discovery, theGREM1 5 ′ regulatory region is now analyzed on many different multi-gene cancer panels, however the data on duplications distinct from the 40 kb duplication remains minimal. Herein we report a novel 24 kb tandem duplic...
Source: Familial Cancer - May 26, 2018 Category: Cancer & Oncology Source Type: research