A new hereditary colorectal cancer network in the Middle East and eastern mediterranean countries to improve care for high-risk families
AbstractColorectal cancer (CRC) has a very high incidence in the western world. Data from registries in the Middle East showed that the incidence of CRC is relatively low in these countries. However, these data also showed that CRC incidence has increased substantially over the past three decades and that a high proportion of cases are diagnosed at an early age (
Source: Familial Cancer - July 6, 2017 Category: Cancer & Oncology Source Type: research

Increased access to TP53 analysis through breast cancer multi-gene panels: clinical considerations
(Source: Familial Cancer)
Source: Familial Cancer - July 5, 2017 Category: Cancer & Oncology Source Type: research

Issues related to family history of cancer at the end of life: a palliative care providers ’ survey
AbstractAddressing the concerns of end-of-life patients or their relatives about their family history of cancer could benefit patients and family members. Little is known about how palliative care providers respond to these concerns. The purpose of this pilot study was to assess palliative care providers ’ knowledge about familial and hereditary cancers and explore their exposure to patients’ and relatives’ concerns about their family history of cancer, and their self-perceived ability to deal with such concerns. A cross-sectional survey was conducted in the Quebec City (Canada) catchment area among palli...
Source: Familial Cancer - July 3, 2017 Category: Cancer & Oncology Source Type: research

Use of the BOADICEA Web Application in clinical practice: appraisals by clinicians from various countries
AbstractThe ‘BOADICEA’ Web Application (BWA) used to assess breast cancer risk, is currently being further developed, to integrate additional genetic and non-genetic factors. We surveyed clinicians’ perceived acceptability of the existing BWA v3. An online survey was conducted through the BOADICEA website , and the British, Dutch, French and Swedish genetics societies. Cross-sectional data from 443 participants who provided at least 50% responses were analysed. Respondents varied in age and, clinical seniority, but mainly comprised women (77%) and genetics professionals (82%). Some expressed negativ ...
Source: Familial Cancer - June 16, 2017 Category: Cancer & Oncology Source Type: research

Early onset renal cell carcinoma in an adolescent girl with germline FLCN exon 5 deletion
We report the youngest patient with BHD-related RCC. This early onset presentation supports genetic testing of at-risk patients and initiation of imaging surveillance for RCC in early adolescence. In addition, future studies are necessary to understand the determinants of reduced penetrance in BHD disease. (Source: Familial Cancer)
Source: Familial Cancer - June 16, 2017 Category: Cancer & Oncology Source Type: research

Somatic mutations of the coding microsatellites within the beta-2-microglobulin gene in mismatch repair-deficient colorectal cancers and adenomas
AbstractIn colorectal cancers (CRCs) with tumour mismatch repair (MMR) deficiency, genes involved in the host immune response that contain microsatellites in their coding regions, including beta-2-microglobulin (B2M), can acquire mutations that may alter the immune response, tumour progression and prognosis. We screened the coding microsatellites withinB2M for somatic mutations in MMR-deficient CRCs and adenomas to determine associations with tumour subtypes, clinicopathological features and survival. Incident MMR-deficient CRCs from Australasian Colorectal Cancer Family Registry (ACCFR) and the Melbourne Collaborative Coh...
Source: Familial Cancer - June 14, 2017 Category: Cancer & Oncology Source Type: research

Potentially pathogenic germline CHEK2 c.319+2T & gt;A among multiple early-onset cancer families
AbstractTo study the potential contribution of genes other thanBRCA1/2, PTEN, andTP53 to the biological and clinical characteristics of multiple early-onset cancers in Norwegian families, including early-onset breast cancer, Cowden-like and Li-Fraumeni-like syndromes (BC, CSL and LFL, respectively). The Hereditary Cancer Biobank from the Norwegian Radium Hospital was used to identify early-onset BC, CSL or LFL for whom no pathogenic variants inBRCA1/2, PTEN, orTP53 had been found in routine diagnostic DNA sequencing. Forty-four cancer susceptibility genes were selected and analyzed by our in-house designed TruSeq amplicon-...
Source: Familial Cancer - June 12, 2017 Category: Cancer & Oncology Source Type: research

Constitutional mismatch repair deficiency and Lynch syndrome among consecutive Arab Bedouins with colorectal cancer in Israel
In conclusion, in this cohort of 24 consecutive Arab Bedouins with CRC, one patient was found to harbor a constitutional mismatch repair deficiency, one patient had LS withMSH6 mutation, and two patients had unresolved loss of MLH1/PMS2 proteins/BRAFwild type phenotype. (Source: Familial Cancer)
Source: Familial Cancer - June 12, 2017 Category: Cancer & Oncology Source Type: research

A single visit multidisciplinary model for managing patients with mutations in moderate and high-risk genes in a community practice setting
AbstractThe introduction of screening for multiple high and moderate risk mutations in genes has resulted in a complex approach to patient care involving multiple disciplines. We sought to describe the feasibility of a single visit multidisciplinary approach to the management of patients with an identified high/moderate risk gene mutation. Patients who presented to our community hospital over a 1-year period who were found to have a high/moderate risk genetic mutation on a screening panel were referred to the High Risk Genetic Clinic. Thirty-five patients were included. The majority were female [34 (97.1%)], Hispanic [22 (...
Source: Familial Cancer - June 9, 2017 Category: Cancer & Oncology Source Type: research

Co-occurrence of Lynch syndrome and juvenile polyposis syndrome confirmed by multigene panel testing
This report adds to the growing body of literature of individuals with multiple inherited cancer gene defects being identified thanks to the increasing implementation of multigene panels with next generation sequencing technologies. (Source: Familial Cancer)
Source: Familial Cancer - June 9, 2017 Category: Cancer & Oncology Source Type: research

A novel TP53 germline inframe deletion identified in a Spanish series of Li-fraumeni syndrome suspected families
AbstractLi-Fraumeni syndrome (LFS) is an autosomal dominant, inherited tumor predisposition syndrome associated with heterozygous germline mutations in theTP53 gene. The molecular diagnosis of LFS is important to develop strategies for early detection and access to the genetic counseling. Our study evaluated germlineTP53 mutations in Spanish families with a history suggestive of LFS. GermlineTP53 alterations in 22 families with a history suggestive of LFS were evaluated by Sanger sequencing and multiplex ligation-dependent probe amplification. Loss of heterozygosity analysis and immunohistochemistry of the protein in the t...
Source: Familial Cancer - June 1, 2017 Category: Cancer & Oncology Source Type: research

RNF43 is mutated less frequently in Lynch Syndrome compared with sporadic microsatellite unstable colorectal cancers
This study assesses the relative frequency ofRNF43 mutations in hereditary colorectal cancers arising in the setting of Lynch syndrome. The entire coding region ofRNF43 was Sanger sequenced in 24 colorectal cancers from 23 patients who either (i) carried a germline mutation in one of the DNA mismatch repair genes (MLH1, MSH6, MSH2, PMS2), or (ii) showed immunohistochemical loss of expression of one or more of the DNA mismatch repair proteins, wasBRAF wild type at V600E, were under 60  years of age at diagnosis, and demonstrated no promoter region methylation forMLH1 in tumor DNA. A validation cohort of 44 colorectal c...
Source: Familial Cancer - June 1, 2017 Category: Cancer & Oncology Source Type: research

Contiguous gene deletion of chromosome 2p16.3-p21 as a cause of Lynch syndrome
We report on a 52-year-old male with Lynch syndrome caused by deletion of chromosome 2p16.3-p21. The patient had intellectual disability and presented with a prostatic adenocarcinoma with an incidentally identified synchronous sigmoid adenocarcinoma that exhibited deficient MMR with an absence of MSH2 and MSH6 protein expression. Family history was unrevealing. Physical exam revealed short stature, brachycephaly with a narrow forehead and short philtrum, brachydactyly of the hands, palmar transverse crease, broad and small feet with hyperpigmentation of the soles. The patient underwent total colectomy with ileorectal anast...
Source: Familial Cancer - May 29, 2017 Category: Cancer & Oncology Source Type: research

Quality of life following prophylactic gynecological surgery: experiences of female Lynch mutation carriers
AbstractLynch syndrome (LS) is a genetic condition conferring an elevated risk of gastrointestinal, gynecologic and other malignancies, often before the age of 50. Current guidelines recommend prophylactic gynecologic surgery to manage inherited cancers for female mutation carriers. Data is lacking on women ’s quality of life following surgery. In this pilot study, we explored how women described their quality of life post-prophylactic gynecologic surgery and the factors that affected post-surgery experiences. A qualitative interview study was the chosen design. Ten female Lynch syndrome mutation car riers were inter...
Source: Familial Cancer - May 27, 2017 Category: Cancer & Oncology Source Type: research

Power of pedigree likelihood analysis in extended pedigrees to classify rare variants of uncertain significance in cancer risk genes
AbstractRare and private variants of uncertain significance (VUS) are routinely identified in clinical panel, exome, and genome sequencing. We investigated the power of single family co-segregation analysis to aid classification of VUS. We simulated thousands of pedigrees using demographics in China and the United States, segregating benign and pathogenic variants. Genotypes and phenotypes were simulated using penetrance models for Lynch syndrome and breast/ovarian cancer. We calculated LOD scores adjusted for proband ascertainment (LODadj), to determine power to yield quantitative evidence for, or against, pathogenicity o...
Source: Familial Cancer - May 22, 2017 Category: Cancer & Oncology Source Type: research

Loss of MSH2 and MSH6 due to heterozygous germline defects in MSH3 and MSH6
We report the first two LS patients harbouring heterozygous germline variants c.1035del and c.2732T>G inMSH3 coincidentally with truncating variants inMSH6. In the patient with truncating germline variants inMSH3 andMSH6, two additional somatic second hits in both genes abrogate all binding partners for the MSH2 protein which might subsequently be degraded. The clinical relevance ofMSH3 germline variants is currently under re-evaluation, and heterozygousMSH3 defects alone do not seem to induce a LS phenotype, but might aggravate theMSH6 phenotype in affected family members. (Source: Familial Cancer)
Source: Familial Cancer - May 20, 2017 Category: Cancer & Oncology Source Type: research

A multi-gene panel study in hereditary breast and ovarian cancer in Colombia
This study describes the frequency and type of germline mutations in hereditary breast and/or ovarian cancer genes in a referral cancer center in Colombia. Eighty-five women referred to the oncogenetics unit of the Instituto de Cancerologia Las Americas in Medellin (Colombia), meeting testing criteria for hereditary breast and ovarian cancer syndrome (NCCN 2015), who had germline testing with a commercial 25-gene hereditary cancer panel, were included in the analysis. Nineteen patients (22.4%) carried a deleterious germline mutation in a cancer susceptibility gene:BRCA1 (7),BRCA2 (8),PALB2 (1),ATM (1),MSH2 (1) andPMS2 (1)....
Source: Familial Cancer - May 20, 2017 Category: Cancer & Oncology Source Type: research

Next generation sequencing is informing phenotype: a TP53 example
AbstractThe increased availability of next generation sequencing (NGS) and multi gene panel testing has resulted in more frequentTP53 testing of families that do not meet classic testing criteria. We investigated testing criteria, family history and result outcome in a cohort of Irish probands undergoingTP53 full sequencing. AllTP53 test requests processed through the national genetic testing laboratory between 2012 and 2014 were retrospectively reviewed. Personal and family cancer histories were collected, including tumour type and age at diagnosis, from two adult cancer genetic services in Ireland. Association between Li...
Source: Familial Cancer - May 16, 2017 Category: Cancer & Oncology Source Type: research

The association of low penetrance genetic risk modifiers with colorectal cancer in lynch syndrome patients: a systematic review and meta-analysis
This study investigates whether low penetrance genetic risk factors may result in phenotype modification in LS patients. To conduct a systematic literature review and meta-analysis to assess the association between low penetrance genetic risk modifiers and CRC in LS patients. A systematic review was conducted of the PubMed and HuGENet databases. Eligibility of studies was determined by pre-defined criteria. Included studies were analysed via the per-allele model and assessed by pooled odds ratios and establishing 95% confidence intervals. Study heterogeneity was assessed via Cochrane ’s Q statistic and I2 values. Pub...
Source: Familial Cancer - May 15, 2017 Category: Cancer & Oncology Source Type: research

Heightened perception of breast cancer risk in young women at risk of familial breast cancer
The objective of this study was to explore the factors that influence perceived personal risk of developing breast cancer (BC) in younger women (
Source: Familial Cancer - May 13, 2017 Category: Cancer & Oncology Source Type: research

Is there a genetic anticipation in breast and/or ovarian cancer families with the germline c.3481_3491del11 mutation?
AbstractThe aim of the current analysis is to evaluate any differences of breast or ovarian cancer age at diagnosis between mothers and daughters carrying the c.3481_3491del11 mutation in theBRCA1 gene. A study cohort of 38 women carrying the c.3481_3491del11 mutation and affected by first breast or ovarian cancer who reported a first breast or ovarian cancer in their mother carrying the c.3481_3491del11 mutation, was identified in 37 different families including members with breast and/or ovarian cancer at the Oncology Institute of Lorraine. Twelve mothers underwent genetic testing. Twenty-five pairs of the 38 mothers-dau...
Source: Familial Cancer - May 10, 2017 Category: Cancer & Oncology Source Type: research

Molecular characterization and clinical interpretation of BRCA1/BRCA2 variants in families from Murcia (south-eastern Spain) with hereditary breast and ovarian cancer: clinical –pathological features in BRCA carriers and non-carriers
AbstractThis is the first study performed in Murcia (south-eastern Spain) in which 592 families with hereditary breast and ovarian cancer were identified thanks to Genetic Counselling Units from this area over 6 years. Diagnostic performance was 18.1% and 194 different genetic variants were obtained. Variants with uncertain significance accounted for only 5.6% of the total number of reports, so our population has been well characterised. In BRCA1 gene, two novel variants were found (c.1859delT and c.3205C  >  T) and the most frequently detected mutations were c.68_69delAG, c.212 + 1G &...
Source: Familial Cancer - May 5, 2017 Category: Cancer & Oncology Source Type: research

Gestational choriocarcinoma associated with a germline TP53 mutation
We report here the first case of a female germlineTP53 mutation carrier who developed, as a first tumour, a lung choriocarcinoma, 6  months after a normal delivery. Molecular analyses established the gestational origin of the choriocarcinoma and showed, within the tumour, the presence of the germline mutantTP53 allele and loss of the wild-type allele. Resistance to methotrexate chemotherapy led to perform a surgical resection of the tumour. In agreement with the permissive role ofTP53 mutations to oncogenic events, this report strongly suggests thatTP53 mutations may promote malignant transformation of proliferating t...
Source: Familial Cancer - May 5, 2017 Category: Cancer & Oncology Source Type: research

TP53 germline and somatic mutations in a patient with fibrolamellar hepatocellular carcinoma
AbstractLi-Fraumeni syndrome is a rare hereditary cancer predisposition syndrome associated with germline pathogenic variants inTP53 gene. The phenotype may vary from classical to variant forms, known as Li-Fraumeni-like phenotypes. We searched for pathogenic variants inTP53 in a 14 year-old female diagnosed with fibrolamellar hepatocellular carcinoma, a rare subtype of hepatocellular carcinoma. The proband is a heterozygote carrier of theTP53 c.467G>A (p.Arg156His) in exon 5, and her mother is an asymptomatic carrier. Analysis of tumor DNA disclosed an additional somatic mutation inTP53, c.461G>A; p.Gly154Asp. TheTP...
Source: Familial Cancer - May 5, 2017 Category: Cancer & Oncology Source Type: research

Placing negative multi-gene panel results into clinical context
(Source: Familial Cancer)
Source: Familial Cancer - April 28, 2017 Category: Cancer & Oncology Source Type: research

General practitioner attitudes towards prescribing aspirin to carriers of Lynch Syndrome: findings from a national survey
AbstractA dose non-inferiority study comparing 100  mg, 300 mg and 600 mg of aspirin for cancer prevention among Lynch Syndrome carriers is underway (Colorectal Adenoma/Carcinoma Prevention Programme trial 3, CaPP3). To guide implementation of the findings, we investigated general practitioner (GP) attitudes towards aspirin prescribing for Lynch Syndrome carriers. We surveyed 1007 UK GPs (9.6% response rate). Using a within-subjects design, GPs read a statement on harms and benefits of aspirin and indicated their willingness to prescribe aspirin at three doses (100 mg, 300 mg, 600 mg). Approxi...
Source: Familial Cancer - April 22, 2017 Category: Cancer & Oncology Source Type: research

How do clinical genetics consent forms address the familial approach to confidentiality and incidental findings? A mixed-methods study
AbstractGenetic test results can be relevant to patients and their relatives. Questions thus arise around whether clinicians regard genetic information as confidential to individuals or to families, and about how they broach this and other issues, including the potential for incidental findings, in consent (forms) for genetic testing. We conducted a content analysis of UK-wide genetic testing consent forms and interviewed 128 clinicians/laboratory scientists. We found that almost all genetic services offered patients multiple, sometimes unworkable, choices on forms, including an option to veto the use of familial genetic i...
Source: Familial Cancer - April 12, 2017 Category: Cancer & Oncology Source Type: research

Importance of updating family cancer history in childhood cancer survivors
This study focused on Li-Fraumeni Syndrome (LFS), a highly penetrant cancer syndrome. Reported family history in a cohort of 648 of cancer survivor cohort (CCS) was examined. Eligible CCS were: (i) aged up to 14 years at diagnosis; (ii) more than 5 years postdiagnosis; (iii) treated for a childhood cancer at the study hospitals in NSW, Australia; (iv) in remission for more than 3 years. CCS completed self-administered que stionnaires. Medical records confirmed diagnosis and treatment-related information. Our findings reveal an increased cancer risk among sibling and relatives of CCS. 91% of siblings diagnosed with cancer w...
Source: Familial Cancer - April 12, 2017 Category: Cancer & Oncology Source Type: research

Universal screening for microsatellite instability in colorectal cancer in the clinical genomics era: new recommendations, methods, and considerations
(Source: Familial Cancer)
Source: Familial Cancer - April 12, 2017 Category: Cancer & Oncology Source Type: research

A Peutz –Jeghers syndrome family associated with sinonasal adenocarcinoma: 28 years follow up report
AbstractPeutz –Jeghers syndrome (PJS) is a rare hereditary disorder characterized by hamartomatous polyps in both of the gastrointestinal tract and mucosal pigmentation. It could increase in risk of intestinal and extra-intestinal neoplasms. We here described three cases of sinonasal polyposis in a PJS family a nd two developed sinonasal type adenocarcinoma. Genetic study revealed a germline STK11/LKB1 mutation on codon 179 (c.C536G, p.P179R) of exon 4. LOH analysis of theLKB1 locus confirms this to be a deleterious mutation. Sinonasal polyposis with malignant transformation could be encountered in PJS patients. Regu...
Source: Familial Cancer - April 8, 2017 Category: Cancer & Oncology Source Type: research

Genetic polymorphisms of NF κB1-94ins/delATTG and NFκBIA-881A/G genes in Egyptian patients with colorectal cancer
AbstractTo assess the association of genetic polymorphisms of NF κB1 and NFκBIA genes with the susceptibility to colorectal cancer (CRC). Subjects included 100 Egyptian patients with CRC (60 males and 40 females) in addition to 85 healthy controls (47 males and 38 females) from the same locality. For all participants, genetic polymorphisms of NFκB1-94ins/delAT TG (rs28362491) and NFκBIA-881A/G (rs3138053) were detected by using restriction fragment length polymorphism polymerase chain reaction (RFLP–PCR). CRC patients showed a significantly higher frequency of the NFκB1-94ins/ins genotyp...
Source: Familial Cancer - April 7, 2017 Category: Cancer & Oncology Source Type: research

A new POT1 germline mutation —expanding the spectrum of POT1 -associated cancers
We present a large family with several family members affected with primary melanomas and dysplastic nevi as well as thyroid cancer and other malignant tumors. Clinical work-up did not reveal a mutation in any of the genes usually considered with evaluation for predisposition to melanoma (BRCA1/2, CDKN2A, CDK4, PTEN, TP53). Whole exome sequencing of five affected family members showed a new variant inPOT1. POT1 is associated with the telomere shelterin complex that regulates telomere protection and telomerase access. Germline mutations inPOT1 were recently shown to be associated with hereditary predisposition to melanoma. ...
Source: Familial Cancer - April 7, 2017 Category: Cancer & Oncology Source Type: research

Identification of novel potential genetic predictors of urothelial bladder carcinoma susceptibility in Pakistani population
AbstractUrothelial bladder carcinoma (UBC) is the most common among urinary bladder neoplasms. We carried out a preliminary study to determine the genetic etiology of UBC in Pakistani population, for this 25 sequence variants from 17 candidate genes were studied in 400 individuals by using polymerase chain reaction-based techniques. Multivariate logistic regression analysis was performed for association analysis of the overall data as well as the data stratified by smoking status, tumor grade and tumor stage. Variants ofGSTM1, IGFBP3, LEPR andACE were found to be associated with altered UBC risk in the overall comparison.C...
Source: Familial Cancer - April 6, 2017 Category: Cancer & Oncology Source Type: research

A case of contralateral breast cancer and skin cancer associated with NBN heterozygous pathogenic variant c.698_701delAACA
AbstractApproximately 39.6% of people will be diagnosed with cancer during their lifetime. Several factors including, lifestyle, environment and genetics may play a role in its development. Understanding these causes will greatly improve treatment methods, prevention, and survival rates of these patients. Our patient, who has a positive family history of cancer, presented with contralateral breast cancer and multiple skin malignancies. Genetic testing revealed a frameshift variant inNBN. This gene encodes the protein, nibrin, which is involved in maintaining genomic stability. Several reports have identified heterozygousNB...
Source: Familial Cancer - April 3, 2017 Category: Cancer & Oncology Source Type: research

All in the family? Communication of cancer survivors with their families
We present data on aspects of family that are most relevant to risk of cancer-related communication and health promotion among family members. Families (a survivor, one first-degree relative and one parent; n  = 313 families) were enrolled in the survey-based study. We assessed multiple aspects of family communication about risk for melanoma among family participants. Families communicate less frequently than desired about cancer risk. Most families do identify a “family health provider” who keep s family data and serves a resource for family members. The reasons given for lack of family communica...
Source: Familial Cancer - April 3, 2017 Category: Cancer & Oncology Source Type: research

Elucidating the clinical significance of two PMS2 missense variants coexisting in a family fulfilling hereditary cancer criteria
AbstractThe clinical spectrum of germline mismatch repair (MMR) gene variants continues increasing, encompassing Lynch syndrome, Constitutional MMR Deficiency (CMMRD), and the recently reportedMSH3-associated polyposis. Genetic diagnosis of these hereditary cancer syndromes is often hampered by the presence of variants of unknown significance (VUS) and overlapping phenotypes. TwoPMS2 VUS, c.2149G>A (p.V717M) and c.2444C>T (p.S815L), were identified in trans in one individual diagnosed with early-onset colorectal cancer (CRC) who belonged to a family fulfilling clinical criteria for hereditary cancer. Clinico-patholog...
Source: Familial Cancer - April 1, 2017 Category: Cancer & Oncology Source Type: research

Expanding the genotype –phenotype spectrum in hereditary colorectal cancer by gene panel testing
AbstractHereditary syndromes causing colorectal cancer include both polyposis and non-polyposis syndromes. Overlapping phenotypes between the syndromes have been recognized and this make targeted molecular testing for single genes less favorable, instead there is a gaining interest for multi-gene panel-based approaches detecting both SNVs, indels and CNVs in the same assay. We applied a panel including 19 CRC susceptibility genes to 91 individuals of six phenotypic subgroups. Targeted NGS-based sequencing of the whole gene regions including introns of the 19 genes was used. The individuals had a family history of CRC or ha...
Source: Familial Cancer - March 19, 2017 Category: Cancer & Oncology Source Type: research

Supporting disclosure of genetic information to family members: professional practice and timelines in cancer genetics
AbstractDisclosure of genetic information within families is one of the longstanding questions under scrutiny in the field of genetics. Most of the probands entrusted with family disclosure succeed in this task, but there are still many problematic cases where it proves difficult. How can professionals help probands disclose this information? What levers can they activate to foster the diffusion of genetic information within families? In the context of a new legal framework concerning this question in France, this paper offers a comprehensive view of the process of genetic counselling in a cancer genetics department. Based...
Source: Familial Cancer - March 14, 2017 Category: Cancer & Oncology Source Type: research

Improved quality of risk-reducing salpingo-oophorectomy in Australasian women at high risk of pelvic serous cancer
AbstractObjectivesThe quality of risk-reducing salpingo-oophorectomy (RRSO) performed in Australasian women was previously reported to be suboptimal. Here we describe the quality of RRSO performed since 2008 in women enrolled in the same cohort and determine whether it has improved.DesignProspective cohort study of women at high risk of pelvic serous cancer (PSC) in kConFab. Eligible women had RRSO between 2008 and 2014 and their RRSO surgical and pathology reports were reviewed. “Adequate” surgery and pathology were defined as complete removal and paraffin embedding of all ovarian and extra-uterine fallopian t...
Source: Familial Cancer - March 11, 2017 Category: Cancer & Oncology Source Type: research

Prevalence of two BRCA1 mutations, 5382insC and 300T   & gt;  G, in ovarian cancer patients from Ukraine
AbstractOvarian cancer is the seventh most common cancer in women worldwide and the leading cause of gynecological malignant diseases-related deaths in women. The most significant risk factor for ovarian cancer is an inherited genetic mutation in one of two genes:breast cancer gene 1 (BRCA1) orbreast cancer gene 2 (BRCA2). The germline mutation c.5266dupC (also known as 5382insC or 5385insC) is the most common mutation among Slavic patients with breast and/or ovarian cancer. Missense mutation c.181T  >  G (also known as 300T >  G or p.C61G) is regarded as the founder change in many Central...
Source: Familial Cancer - March 11, 2017 Category: Cancer & Oncology Source Type: research

Lower gastrointestinal neuroendocrine neoplasms associated with hereditary cancer syndromes: a case series
We report the first case series of six patients with lower GI NENs who were diagnosed with hereditary GI cancer syndromes by germline testing. Two patients presented with poorly differentiated rectal neuroendocrine carcinoma (NECs) with colonic polyposis and were found to have Familial Adenomatous Polyposis and MYH-Associated Polyposis, respectively. Three patients with colorectal NENs (one well differentiated neuroendocrine tumor, NET, and two NECs), all of which displayed abnormal immunohistochemistry for mismatch repair proteins, were diagnosed with Lynch syndrome. One patient with a goblet cell carcinoid was diagnosed ...
Source: Familial Cancer - March 10, 2017 Category: Cancer & Oncology Source Type: research

Gastric tumours in FAP
AbstractGastric cancer is not a recognised extra-colonic manifestation of FAP, except in countries with a high prevalence of gastric cancer. Data regarding gastric adenomas in FAP are sparse. The aim of this study was to review the clinical characteristics of gastric tumours occurring within an FAP population from the largest European polyposis registry. All patients that developed a gastric adenoma or carcinoma were identified from a prospectively maintained registry database. The primary outcome measure was the occurrence of gastric adenoma or adenocarcinoma. Secondary outcomes includedAPC mutation, tumour stage, managem...
Source: Familial Cancer - March 7, 2017 Category: Cancer & Oncology Source Type: research

Patients with negative multi-gene panel testing: a back to the future paradox?
(Source: Familial Cancer)
Source: Familial Cancer - March 3, 2017 Category: Cancer & Oncology Source Type: research

High-risk individuals ’ perceptions of reproductive genetic testing for CDH1 mutations
AbstractReproductive genetic testing- PreNatal Diagnosis (PND) and Preimplantation Genetic Diagnosis (PGD) —forCDH1 mutations associated with Hereditary Diffuse Gastric Cancer (HDGC)is available in the UK. This qualitative interview study examined high-risk individuals ’ (n = 35) views ofCDH1 reproductive genetic testing. Interviewees generally regarded reproductive genetic testing as an acceptable form of HDGC risk management. However, some were concerned that their genetic risks required them to plan reproduction and anticipated difficulties communicating this to reproductive partners. Individua...
Source: Familial Cancer - February 15, 2017 Category: Cancer & Oncology Source Type: research

Gastric cancer in FAP: a concerning rise in incidence
We describe a recent, sudden increase in the incidence of gastric cancer in FAP. Seven of the ten cases were diagnosed in the last 20  months. Comparing our population to the SEER database for gastric cancer, the standardized incidence ratio is 140. All cases arose in patients with a carpeting of FGP and associated with large mounds of proximal gastric polyps. Nearly all patients were under upper endoscopic surveillance. This is  a concerning observation and reflects a change in the phenotypic presentation of FAP in Western patients. (Source: Familial Cancer)
Source: Familial Cancer - February 9, 2017 Category: Cancer & Oncology Source Type: research

A lesson from a reported pathogenic variant in Peutz-Jeghers syndrome: a case report
In this study, compound heterozygous variants ofLKB1, c.890G  >  A/ c.1062C >  G and del(exon1)/ c.1062C >  G, were identified in two sporadic Chinese PJS cases respectively. Although all these three variants had been related to the autosomal dominant PJS in previous studies, all evidences collected in this study including de novo data, segregation data, population data, in-silico data, and functional data indicated that del(exon1) and c.890G >  A are pathogenic in these two PJS families rather than c.1062C >  G. This finding would contrib...
Source: Familial Cancer - February 9, 2017 Category: Cancer & Oncology Source Type: research

Biallelic BRCA2 mutations in two black South African children with Fanconi anaemia
We present two cases of black South African patients with FA diagnosed with biallelicBRCA2 mutations and discuss the phenotypic consequences and implications for them and their families. Recognition of this severe end of the phenotypic spectrum of FA is critical in allowing for confirmation of the diagnosis as well as cascade screening and appropriate care of family members. (Source: Familial Cancer)
Source: Familial Cancer - February 9, 2017 Category: Cancer & Oncology Source Type: research

The association between prognosis of breast cancer and first-degree family history of breast or ovarian cancer: a systematic review and meta-analysis
AbstractWhether a positive family history of breast cancer or ovarian cancer (FHBOC) would affect the prognosis of breast cancer is still up for debate and further study. This meta-analysis was performed to clarify this issue. We reviewed two databases (PubMed and CNKI) for research articles published at any time from the inception of these databases to April 1, 2016 for articles detecting the impact of FHBOC on the prognosis of breast cancer. A meta-analysis was conducted to generated combined hazard ratios (HR) with 95% confidence intervals (CI) for overall survival (OS) and breast cancer-specific survival (BCSS). Eighte...
Source: Familial Cancer - February 7, 2017 Category: Cancer & Oncology Source Type: research

Universal screening for Lynch syndrome among patients with colorectal cancer: patient perspectives on screening and sharing results with at-risk relatives
This study indicates that patients are interested in being screened for LS and that sharing information on the risk of LS with at-risk family members is not a significant barrier. These findings provide novel insight into patient perspectives about screening for LS and can guide successful implementation of universal screening programs. (Source: Familial Cancer)
Source: Familial Cancer - February 7, 2017 Category: Cancer & Oncology Source Type: research

Correlation between germline mutations in MMR genes and microsatellite instability in ovarian cancer specimens
AbstractA high proportion of ovarian cancers from women who carry germline mutations in mismatch repair (MMR) genes demonstrate microsatellite instability (MSI). The utility of pre-screening ovarian cancer specimens for MSI to identify potential patients for germline screening for MMR mutations is uncertain. 656 women with malignant ovarian cancer underwent both MSI testing and germline mutation testing for large rearrangements in three MMR genes,MLH1, MSH2 andMSH6. Germline DNA sequencing data for the same genes was available. Among the 656 women, only four (0.6%) carried a clearly pathogenic MMR mutation. All four cancer...
Source: Familial Cancer - February 7, 2017 Category: Cancer & Oncology Source Type: research