Delineating a new feature of constitutional mismatch repair deficiency (CMMRD) syndrome: breast cancer
We report on two sisters originally suspected of having CMMRD syndrome due to their history of colonic polyps and NF1 associated skin findings, both were subsequently found to have biallelicMSH6 mutations. After years of CMMRD syndrome follow-up, the proband was diagnosed with breast cancer at age 29, while her sister was diagnosed with a glioblastoma at age 27. Immunohistochemistry analysis on the breast tumor tissue revealed weak MSH6 protein staining. Exome sequencing revealed a hypermutated breast tumor and an ultra-hypermutated brain tumor. Multi-gene panel testing was also performed and revealed no additional mutatio...
Source: Familial Cancer - May 21, 2018 Category: Cancer & Oncology Source Type: research

Sarcoma in neurofibromatosis 2: case report and review of the literature
We report a 22-year-old man who presented with retroperitoneal and spinal high-grade sarcomas with epithelial features. Samples showed a mixed epithelioid and spindled cell content with little associated matrix and inconclusive immunochemistry. Genetic analysis of a schwannoma and matched blood samples demonstrated a constitutional de novo substitution at the splice donor site of intron 8 of the NF2 gene and aa acquired large deletion of the entire NF2 gene as a second hit, with some loss ofSMARCB1. The sarcoma also showed evidence of loss ofSMARCB1 andNF2 with loss of INI1 staining. Unfortunately the mass was unresectable...
Source: Familial Cancer - May 14, 2018 Category: Cancer & Oncology Source Type: research

Report of a bi-allelic truncating germline mutation in TP53
We report an infant from a consanguineous family who presented with synchronous malignancies. Remarkably, he carries a homozygous germlineTP53 mutation (NM_000546.4:c.52delA), predicted to cause protein truncation. The family history is consistent with Li-Fraumeni syndrome. (Source: Familial Cancer)
Source: Familial Cancer - May 8, 2018 Category: Cancer & Oncology Source Type: research

Physician interpretation of variants of uncertain significance
AbstractA growing number of physicians will interact with genetic test results as testing becomes more commonplace. While variants of uncertain significance can complicate results, it is equally important that physicians understand how to incorporate these results into clinical care. An online survey was created to assess physician self-reported comfort level with genetics and variants of uncertain significance. Physicians were asked to respond to three case examples involving genetic test results. The survey was sent to 488 physicians at Mayo Clinic FL on 8/16/2017. Physicians from all specialties were invited to particip...
Source: Familial Cancer - May 2, 2018 Category: Cancer & Oncology Source Type: research

Reminders of cancer risk and pain catastrophizing: relationships with cancer worry and perceived risk in women with a first-degree relative with breast cancer
We examined the degree to which persistent breast pain and experience as a cancer caregiver were related to cancer worry and perceived risk in first-degree relatives of women with breast cancer (N = 85) and how catastrophic thoughts about breast pain could impact these relationships. There was a significant interaction between persistent breast pain and pain catastrophizing in predicting cancer worry (p = .03); among women who engaged in pain catastrophizing, cancer worry remained high even in the absence of breast pain. Pain catastrophizing also moderated the relationships between caregiving in...
Source: Familial Cancer - April 20, 2018 Category: Cancer & Oncology Source Type: research

Prevalence of thyroid diseases in familial adenomatous polyposis: a systematic review and meta-analysis
AbstractThyroid cancer (TC) is a known extra-intestinal manifestation and contributes to the mortality and morbidity in patients with familial adenomatous polyposis (FAP). Its exact prevalence is not well established and recent studies have shown an increasing number of TC in this patient population. The prevalence of benign thyroid masses and endocrinologic thyroid disorders are also poorly described. We conducted a systematic review and meta-analysis by using a random-effects model to characterize TC and estimated the prevalence of thyroid diseases in FAP patients. Twelve studies (n  = 9821) were included. ...
Source: Familial Cancer - April 16, 2018 Category: Cancer & Oncology Source Type: research

Unsolicited information letters to increase awareness of Lynch syndrome and familial colorectal cancer: reactions and attitudes
AbstractDissemination of information on a genetically increased risk should according to guidelines primarily be family-mediated. Incomplete and incorrect information spread has, however, been documented and implies missed possibilities for prevention. In Denmark, the national HNPCC register has been granted an exception to send unsolicited letters with information on hereditary colorectal cancer and an invitation to genetic counseling to members of families with familial and hereditary colorectal cancer. To evaluate this approach, we investigated reactions and attitudes to unsolicited letters in 708 members of families wi...
Source: Familial Cancer - April 12, 2018 Category: Cancer & Oncology Source Type: research

Hemangioblastoma in Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome: a phenotypic overlap between VHL and HLRCC Syndromes
We present a case study of hemangioblastoma occurrence in a Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome patient and propose it as possible evidence of a phenotypic overlap between von Hippel Lindau and Hereditary Leiomyomatosis and Renal Cell Cancer Syndromes due to their overlapping role in the biochemical regulation of hypoxia inducible factor alpha. (Source: Familial Cancer)
Source: Familial Cancer - April 4, 2018 Category: Cancer & Oncology Source Type: research

Screening of BMPR1a for pathogenic mutations in familial colorectal cancer type X families from Newfoundland
AbstractThe Canadian province of Newfoundland and Labrador (NL) reports one of the highest incidence rates of familial colorectal cancer (CRC) worldwide. The NL population is an invaluable resource for studying genetic disorders because of a unique ancestry, and a willingness to participate in research studies. Familial colorectal cancer type X (FCCTX) describes a cluster of families with strong predisposition for CRC, of unknown etiology. A putative link between FCCTX andBMPR1a mutations has been identified in the Finnish population; however these findings have not been independently replicated. To investigate a potential...
Source: Familial Cancer - April 1, 2018 Category: Cancer & Oncology Source Type: research

Screening for Lynch syndrome in young Saudi colorectal cancer patients using microsatellite instability testing and next generation sequencing
AbstractIndividuals with Lynch syndrome (LS) have germline variants in DNA mismatch repair (MMR) genes that confer a greatly increased risk of colorectal cancer (CRC), often at a young age. Identification of these individuals has been shown to increase their survival through improved surveillance. We previously identified 33 high risk cases for LS in the Saudi population by screening for microsatellite instability (MSI) in the tumor DNA of 284 young CRC patients. The aim of the present study was to identify MMR gene variants in this cohort of patients. Peripheral blood DNA was obtained from 13 individuals who were at high ...
Source: Familial Cancer - April 1, 2018 Category: Cancer & Oncology Source Type: research

Germline CDH1 mutations are a significant contributor to the high frequency of early-onset diffuse gastric cancer cases in New Zealand M āori
AbstractNew Zealand M āori have a considerably higher incidence of gastric cancer compared to non-Māori, and are one of the few populations worldwide with a higher prevalence of diffuse-type disease. Pathogenic germlineCDH1 mutations are causative of hereditary diffuse gastric cancer, a cancer predisposition syndrome primarily characterised by an extreme lifetime risk of developing diffuse gastric cancer. PathogenicCDH1 mutations are well described in M āori families in New Zealand. However, the contribution of these mutations to the high incidence of gastric cancer is unknown. We have used next-generation sequencing, S...
Source: Familial Cancer - March 27, 2018 Category: Cancer & Oncology Source Type: research

Clinical and pathologic characteristics of breast cancer patients carrying the c.3481_3491del11 mutation
AbstractTumor characteristics are used today to evaluate the possibility of mutation and to target mutation screening in families with high risk of breast and/or ovarian cancer. We studied the breast tumor profile associated to the c.3481_3491del11 French founder effect mutation on theBRCA1 gene to an attempt to identify any particularity or difference when comparing it to that related to otherBRCA1 mutations. Within the population who were referred to our oncogenetic clinic at the Lorraine Oncology Institute in France and who underwent genetic testing between 1994 and 2012, we identified 404 women carrying aBRCA1 mutation...
Source: Familial Cancer - March 17, 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 - February 27, 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 - February 20, 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 - February 15, 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 - February 14, 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 - February 8, 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 - February 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 - January 29, 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 - January 24, 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 - January 24, 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 - January 22, 2018 Category: Cancer & Oncology Source Type: research

Letter to the editor
(Source: Familial Cancer)
Source: Familial Cancer - January 12, 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 - January 4, 2018 Category: Cancer & Oncology Source Type: research

The role of screening MRI in the era of next generation sequencing and moderate-risk genetic mutations
AbstractWith the advent of next-generation sequencing, the ability to rapidly analyze numerous genes simultaneously has led to the creation of large cancer gene panels. Some of these genes, likeBRCA1 andBRCA2, have been heavily researched and have well-established management guidelines. Other more newly established genes, likeATM, CHEK2, andPALB2, have previously had less robust research surrounding them which has limited the ability to create accurate risk estimates. With their inclusion on gene panels, there has been more pressure to produce management guidelines for patients discovered to carry pathogenic variants in th...
Source: Familial Cancer - January 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 - December 29, 2017 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 - December 5, 2017 Category: Cancer & Oncology Source Type: research

The importance of a well-structured pancreatic screening program for familial and hereditary pancreatic cancer
(Source: Familial Cancer)
Source: Familial Cancer - December 4, 2017 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 - November 30, 2017 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 - November 30, 2017 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 - November 17, 2017 Category: Cancer & Oncology Source Type: research

Germline variant in MSX1 identified in a Dutch family with clustering of Barrett ’s esophagus and esophageal adenocarcinoma
AbstractThe vast majority of esophageal adenocarcinoma cases are sporadic and caused by somatic mutations. However, over the last decades several families have been identified with clustering of Barrett ’s esophagus and esophageal adenocarcinoma. This observation suggests that one or more hereditary factors may play a role in the initiation of Barrett’s esophagus and esophageal adenocarcinoma in these families. A Dutch family with clustering of Barrett’s esophagus and esophageal adenocarcinom a was identified. Normal DNA obtained from the proband diagnosed with Barrett’s esophagus was analyzed with ...
Source: Familial Cancer - November 13, 2017 Category: Cancer & Oncology Source Type: research

Universal determination of microsatellite instability using BAT26 as a single marker in an Argentine colorectal cancer cohort
AbstractMicrosatellite instability (MSI) is a hallmark tool for Lynch syndrome (LS) screening and a prognostic marker for sporadic colorectal cancer (CRC). In regions with limited resources and scarce CRC molecular characterization as South America, the implementation of universal MSI screening is under debate for both its purposes. We sought to estimate the frequency of BAT26 in colorectal adenocarcinomas and to determine associated clinical and histological features. Consecutive patients from a CRC registry were included. BAT26 determination was performed in all cases; if instability was found, immunohistochemistry (IHC)...
Source: Familial Cancer - November 11, 2017 Category: Cancer & Oncology Source Type: research

Association between miR-146a rs2910164 polymorphism and specific cancer susceptibility: an updated meta-analysis
This article will discuss the association between miR-146 rs2910164 polymorphism and cancer susceptibility in 38 independent case-control studies from 34905 individuals. The 38 case-control studies which were searched from PubMed were used for conducting a meta-analysis. There were 14670 cases and 20235 controls. ORs and 95% CIs were used for reflecting the strength of association between miR-146a rs2910164 polymorphism and cancer susceptibility. Subgroup analysis based on the cancer type, ethnicity and study designs. All analysis were performed by using the Stata 11.0 software. MiR-146a rs2910164 polymorphism and overall ...
Source: Familial Cancer - November 10, 2017 Category: Cancer & Oncology Source Type: research

Information and support needs of young women regarding breast cancer risk and genetic testing: adapting effective interventions for a novel population
In this report, we describe our adaptation of a previously-studied behavioral intervention for this population, utilizing a systematic approach outlined by the Centers for Disease Control and Prevention. First, we assessed the information needs and levels of distress in this population and correlates of this distress. These data then were used to inform the adaptation and piloting of a three-session telephone-based peer coaching intervention. One hundred young women (M age  = 25 years) who were first or second degree relatives ofBRCA1/2 mutation carriers participated. Sixty-three percent of the sample en...
Source: Familial Cancer - November 9, 2017 Category: Cancer & Oncology Source Type: research

Excluding Lynch syndrome in a female patient with metachronous DNA mismatch repair deficient colon- and ovarian cancer
AbstractPatients synchronously or metachronously presenting with ovarian and colon cancer can pose diagnostic challenges. A primary colon carcinoma can metastasize to one or both ovaries, two independent primary tumors can arise or an ovarian carcinoma can metastasize to the colon. Clinical and immunohistochemical characterization can aid the diagnosis. Recently, we reported that in difficult cases finding pathogenicAPC variants supports a colonic origin.In this case report we describe the clinical history of a female patient suspected for Lynch syndrome. She was diagnosed with a bilateral ovarian cancer at age 44, followe...
Source: Familial Cancer - November 9, 2017 Category: Cancer & Oncology Source Type: research

Genotype phenotype correlation in Asian Indian von Hippel –Lindau (VHL) syndrome patients with pheochromocytoma/paraganglioma
In conclusion, PCC/PGL are rare in patients with largeVHL deletions and if occur are most likely to be solitary. Patients with bilateral PCC or multifocal PCC/PGL are least likely to have largeVHL deletions. Our study also provides additional evidence for existence of the phenomenon of anticipation in VHL syndrome. (Source: Familial Cancer)
Source: Familial Cancer - November 9, 2017 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 - November 8, 2017 Category: Cancer & Oncology Source Type: research

Development of a high risk pancreatic screening clinic using 3.0  T MRI
We describe the establishment of a comprehensive multidisciplinary screening program using 3.0  T MRI. Criteria for screening included the presence of PC in: ≥ 2 first degree relatives (FDR), 1 FDR and 1 s degree relative (SDR), ≥ 3 any degree relatives (ADR), or any known hereditary cancer syndrome with increased PC risk. Imaging with 3.0 T MRI was performed routinely and endoscopic u ltrasound was used selectively. Screening was completed in 75 patients (pts). Hereditary cancer syndromes were present in 42 (56%) of the 75 pts: BRCA2 (18), ATM (8), BRCA1 (6), CDKN2A (4), PALB2 (3), Lynch (2), and Peut...
Source: Familial Cancer - November 3, 2017 Category: Cancer & Oncology Source Type: research

Cost-effectiveness evaluation of pre-counseling telephone interviews before face-to-face genetic counseling in cancer genetics
AbstractOne of the main challenges in cancer genetics is responding to the exponential demand for genetic counseling, especially in patients with breast and/or ovarian cancer. To address this demand, we have set up a new procedure, based on pre-genetic counseling telephone interviews (PTI) followed by routing of patients: D1, a PTI is scheduled within 14  days; D7–D14, genetic counselors perform a 20 min PTI in order to establish a pre-genetic counseling file, by collecting personal and family medical historyvia a structured questionnaire and; D10 –17, routing: pre-genetic counseling appointment files...
Source: Familial Cancer - October 27, 2017 Category: Cancer & Oncology Source Type: research

Phenotypic and genotypic heterogeneity of Lynch syndrome: a complex diagnostic challenge
AbstractLynch syndrome is the hereditary disorder that most frequently predisposes to colorectal cancer as well as predisposing to a number of extracolonic cancers, most prominently endometrial cancer. It is caused by germline mutations in the mismatch repair genes. Both its phenotype and genotype show marked heterogeneity. This review gives a historical overview of the syndrome, its heterogeneity, its genomic landscape, and its implications for complex diagnosis, genetic counseling and putative implications for immunotherapy. (Source: Familial Cancer)
Source: Familial Cancer - October 25, 2017 Category: Cancer & Oncology Source Type: research

Corrections to: Use of the BOADICEA Web Application in clinical practice: appraisals by clinicians from various countries
AbstractThe article “Use of the BOADICEA Web Application in clinical practice: appraisals by clinicians from various countries” written by Anne Brédart · Jean‑Luc Kop · Antonis C. Antoniou · Alex P. Cunningham · Antoine De Pauw ·Marc Tischkowitz · Hans Ehrencrona · Sylvie Dolbeault · Léonore Robieux · Kerstin Rhiem ·Douglas F. Easton · Peter Devilee · Dominique Stoppa‑Lyonnet· Rita Schmutlzer, was originally published electronically on the publisher’s internet portal (currently SpringerLink) on 16t...
Source: Familial Cancer - October 25, 2017 Category: Cancer & Oncology Source Type: research

Targeted massively parallel sequencing characterises the mutation spectrum of PALB2 in breast and ovarian cancer cases from Poland and Ukraine
This study is consistent with previous reports thatPALB2:c.509_510del andPALB2:c.172_175del are recurrent mutations associated with breast cancer predisposition in Polish women with a family history of the disease. Our study contributes to the accumulating evidence indicating thatPALB2 should be included in genetic testing for breast cancer susceptibility in these populations to enhance risk assessment and management of women at high-risk of developing breast cancer. This data could also contribute to ongoing work that is assessing the possible association between ovarian cancer risk andPALB2 mutations for which there is c...
Source: Familial Cancer - October 19, 2017 Category: Cancer & Oncology Source Type: research

Cancer risk management in Tasmanian women with BRCA1 and BRCA2 mutations
In this study we surveyed 193BRCA1/2 mutation carriers in the state of Tasmania to determine the uptake of cancer risk-reducing strategies and what factors might influence women ’s decisions in relation to both gynaecological and breast surgery. We observed that uptake of risk management strategies varied depending on the strength of the recommendation in the national guidelines. Uptake rates were>  90% for strategies which are strongly recommended, such as breast screening by MRI/mammogram and bilateral salpingo-oophorectomy, and were unaffected by demographic factors such as socio-economic disadvantage an...
Source: Familial Cancer - October 16, 2017 Category: Cancer & Oncology Source Type: research

Penetrance of a rare familial mutation predisposing to papillary thyroid cancer
We present a large family with NMTC in which we had previously described a culpable mutation. Participants provided their personal medical history and family history. The germline 4q32 A >  C mutation was detected in 34 of 68 tested individuals. Age-specific penetrance of thyroid cancer and benign thyroid disease was determined using the inverted Kaplan–Meier method of segregation analysis. Individuals who tested positive for the 4q32 mutation have a 68.9% (95% CI 46.5–88.7) ris k of developing thyroid cancer by age 70 and a 65.3% (95% CI 46.0–83.8) risk of developing benign thyroid disea...
Source: Familial Cancer - October 12, 2017 Category: Cancer & Oncology Source Type: research

Family history influences the tumor characteristics and prognosis of breast cancers developing during postmenopausal hormone therapy
AbstractLong term use of postmenopausal hormone therapy (HT) has been reported to increase breast cancer risk. On the other hand, observational studies suggest that breast cancers diagnosed during HT may have a more favorable prognosis. While family history is a risk factor for breast cancer, and genetic factors also influence prognosis, the role of family history in combination with HT use has been little studied. We investigated the relationship between HT, family history, and prognosis in 584 (267 exposed) familial and 952 (460 exposed) non-familial breast cancer cases, using three survival end points: death from breast...
Source: Familial Cancer - October 10, 2017 Category: Cancer & Oncology Source Type: research

Whole body magnetic resonance imaging (WB-MRI) and brain MRI baseline surveillance in TP53 germline mutation carriers: experience from the Li-Fraumeni Syndrome Education and Early Detection (LEAD) clinic
The objective of this study was to determine the diagnostic performance of whole body MRI (WB-MRI) and dedicated brain MRI screening as part of a comprehensive screening clinic called Li-Fraumeni Education and Early Detection (LEAD) at MD Anderson Cancer Center. Adult ( ≥21 year old) and pediatric (
Source: Familial Cancer - October 7, 2017 Category: Cancer & Oncology Source Type: research

Inherited DNA repair gene mutations detected by tumor next generation sequencing in urinary tract cancers
AbstractInterpretation of next-generation sequencing (NGS) of tumor tissue in patients with advanced Urinary Tract Cancer (UTC) is performed to guide treatment selection but may reveal pathogenic variants with germline implications. We identified three patients with UTC with unexpected germline DNA repair gene mutations. Specific testing for these was prompted by the detection of these mutations by tumor NGS. All three patients were nonsmokers with a strong family history of cancer. Two patients had upper tract UTC with age at diagnosis in the 40  s. One had a family history suggestive of hereditary breast/ovarian pre...
Source: Familial Cancer - September 18, 2017 Category: Cancer & Oncology Source Type: research

Mutations in context: implications of BRCA testing in diverse populations
This article discusses the potential impact of genetic testing on population health, focusing in particular on the mutational spectrum of breast cancer susceptibility genes in diverse populations. We identify the need for improved access to, and increased investment in, comprehensive cancer risk assessment and genetic testing as well as cancer control measures that take into account lifestyle, environmental, and social factors in understudied minority groups. (Source: Familial Cancer)
Source: Familial Cancer - September 16, 2017 Category: Cancer & Oncology Source Type: research

Germline mutations in lung cancer and personalized medicine
(Source: Familial Cancer)
Source: Familial Cancer - September 15, 2017 Category: Cancer & Oncology Source Type: research