Discovery of mutations in homologous recombination genes in African-American women with breast cancer
AbstractAfrican-American women are more likely to develop aggressive breast cancer at younger ages and experience poorer cancer prognoses than non-Hispanic Caucasians. Deficiency in repair of DNA by homologous recombination (HR) is associated with cancer development, suggesting that mutations in genes that affect this process may cause breast cancer. Inherited pathogenic mutations have been identified in genes involved in repairing DNA damage, but few studies have focused on African-Americans. We screened for germline mutations in seven HR repair pathway genes in DNA of 181 African-American women with breast cancer, evalua...
Source: Familial Cancer - September 2, 2017 Category: Cancer & Oncology Source Type: research

Cancer patients ’ intentions towards receiving unsolicited genetic information obtained using next-generation sequencing
AbstractNext-generation sequencing (NGS) can be used to generate information about a patient ’s tumour and personal genome. This powerful diagnostic tool provides solicited and unsolicited hereditary genetic (risk) information that could have consequences for cancer patients and their quality of life. A well-defined approach for returning appropriate genetic risk information is needed in personalized cancer care. A qualitative design with semi-structured interviews was used. We conducted interviews with 24 Dutch patients with different types of cancer, both NGS-experienced and NGS-inexperienced, to learn their intent...
Source: Familial Cancer - August 29, 2017 Category: Cancer & Oncology Source Type: research

Sporadic endometrial adenocarcinoma with MMR deficiency due to biallelic MSH2 somatic mutations
We report t he case of a woman with an early-onset endometrial adenocarcinoma who was suspected to be affected with Lynch syndrome based on tumor dMMR phenotype (MSI associated with loss of expression of MSH2 and MSH6 proteins). After complete germline and somatic evaluations, this phenotype was eventually expl ained by twoMSH2 somatic mutations and the diagnosis of Lynch-like syndrome due to an unidentifiedMSH2 germline mutation was ruled out. Somatic mosaicism at low mutation rate was unlikely as no mutation was detected by DNA analysis from various tissue samples. Nevertheless, the three patient ’s children were t...
Source: Familial Cancer - August 17, 2017 Category: Cancer & Oncology Source Type: research

Immunohistochemical null-phenotype for mismatch repair proteins in colonic carcinoma associated with concurrent MLH1 hypermethylation and MSH2 somatic mutations
AbstractMicrosatellite instability, a well-established driver pathway in colorectal carcinogenesis, can develop in both sporadic and hereditary conditions via different molecular alterations in the DNA mismatch repair (MMR) genes. MMR protein immunohistochemistry (IHC) is currently widely used for the detection of MMR deficiency in solid tumors. The IHC test, however, can show varied staining patterns, posing challenges in the interpretation of the staining results in some cases. Here we report a case of an 80-year-old female with a colonic adenocarcinoma that exhibited an unusual “null” IHC staining pattern wi...
Source: Familial Cancer - August 17, 2017 Category: Cancer & Oncology Source Type: research

Mutational analysis of the RB1 gene and the inheritance patterns of retinoblastoma in Jordan
In conclusion, in addition to all bilateral RB patients in our cohort, 30% of unilateral cases showed germline mutation. Almost half (47%) of germline cases had inherited disease from affected (6%) parent or unaffected carrier (94%). Therefore molecular screening is critical for the genetic counseling regarding the risk for inherited RB in both unilatera l and bilateral cases including those with no family history. (Source: Familial Cancer)
Source: Familial Cancer - August 12, 2017 Category: Cancer & Oncology Source Type: research

A germline missense mutation in exon 3 of the MSH2 gene in a Lynch syndrome family: correlation with phenotype and localization assay
AbstractLynch syndrome is caused by germline mutations in any of the MisMatch Repair (MMR) genes. About 37% ofMSH2 variants are missense variants causing single amino-acid substitutions. Whether missense variants affect the normal function of MMR proteins is crucial both to provide affected families a more accurate risk assessment and to offer predictive testing to family members. Here we report one family, fulfilling both Amsterdam I and II criteria and Bethesda guidelines, referred to our center for genetic counselling. The proband and some of her relatives have been investigated for microsatellite instability (MSI), imm...
Source: Familial Cancer - August 7, 2017 Category: Cancer & Oncology Source Type: research

p53 signaling pathway polymorphisms, cancer risk and tumor phenotype in TP53 R337H mutation carriers
In conclusion, our results suggest that MDM2 SNP 309 may contribute to the LFL phenotype and also to an earlier age at diagnosis of ACC and BC cancer in carriers of the R337H founder mutation. (Source: Familial Cancer)
Source: Familial Cancer - July 29, 2017 Category: Cancer & Oncology Source Type: research

Pancreatic adenocarcinoma with a germline PTEN p.Arg234Gln mutation
AbstractA minor fraction of pancreatic ductal adenocarcinoma (PDAC) develops in association with germline mutations of the genes responsible for inherited cancer syndromes. However, the PDAC that has a germlinePTEN mutation has not received much attention. Genome-wide whole exome sequencing was performed on germline and somatic DNA from an 82-year-old woman who had developed a solid pancreatic cancer but did not show characteristic findings of PTEN hamartoma tumor syndromes (PHTS). Histology of the resected pancreatic tumor showed unique PDAC findings of primarily dendriform structures and dense fibrous tissue, accompanied...
Source: Familial Cancer - July 28, 2017 Category: Cancer & Oncology Source Type: research

Erratum to: A new hereditary colorectal cancer network in the Middle East and eastern Mediterranean countries to improve care for high-risk families
(Source: Familial Cancer)
Source: Familial Cancer - July 27, 2017 Category: Cancer & Oncology Source Type: research

Remarkable effects of imatinib in a family with young onset gastrointestinal stromal tumors and cutaneous hyperpigmentation associated with a germline KIT -Trp557Arg mutation: case report and literature overview
AbstractGastrointestinal stromal tumors (GISTs) occur mostly sporadically. GISTs associated with a familial syndrome are very rare and are mostly wild type forKIT and platelet-derived growth factor alpha (PDGFRA). To date 35 kindreds and 8 individuals have been described with GISTs associated with germlineKIT mutations. This is the third family described with a germline p.Trp557Arg mutation in exon 11 of theKIT gene. The effect of imatinib in patients harboring a germlineKIT mutation has been rarely described. Moreover, in some studies imatinib treatment was withheld considering the lack of evidence for efficacy of this tr...
Source: Familial Cancer - July 14, 2017 Category: Cancer & Oncology Source Type: research

A comparison of cosegregation analysis methods for the clinical setting
AbstractQuantitative cosegregation analysis can help evaluate the pathogenicity of genetic variants. However, genetics professionals without statistical training often use simple methods, reporting only qualitative findings. We evaluate the potential utility of quantitative cosegregation in the clinical setting by comparing three methods. One thousand pedigrees each were simulated for benign and pathogenic variants inBRCA1 andMLH1 using United States historical demographic data to produce pedigrees similar to those seen in the clinic. These pedigrees were analyzed using two robust methods, full likelihood Bayes factors (FL...
Source: Familial Cancer - July 10, 2017 Category: Cancer & Oncology Source Type: research

The spectrum of genetic variants in hereditary pancreatic cancer includes Fanconi anemia genes
AbstractApproximately 5 –10% of all pancreatic cancer patients carry a predisposing mutation in a known susceptibility gene. Since>90% of patients present with late stage disease, it is crucial to identify high risk individuals who may be amenable to early detection or other prevention. To explore the spectrum of hereditary pancreatic cancer susceptibility, we evaluated germline DNA from pancreatic cancer participants (n  = 53) from a large hereditary cancer registry. For those without a known predisposition mutation gene (n = 49), germline next generation sequencing was completed using...
Source: Familial Cancer - July 8, 2017 Category: Cancer & Oncology Source Type: research

Association of genetic variations in RTN4 3 ′-UTR with risk for clear cell renal cell carcinoma
AbstractNogo proteins play an important role in the apoptosis of cells, especially in tumor cells. The present study was conducted to evaluate whether the TATC (rs71682980) and CAA (rs34917480) insertion/deletion polymorphisms ofRTN4 3 ′-UTR are associated with clear cell renal cell carcinoma (ccRCC). These two polymorphisms were genotyped in 308 ccRCC patients and 466 healthy controls by polymerase chain reaction polyacrylamide gel electrophoresis (PCR-PAGE). Significantly reduced ccRCC risk was observed to be associated with t he TATCins/ins genotype carriers (Versus TATCdel/del: adjusted OR 0.53, 95% CI 0.32 &ndas...
Source: Familial Cancer - July 7, 2017 Category: Cancer & Oncology Source Type: research

Novel BRCA1 splice-site mutation in ovarian cancer patients of Slavic origin
We report a novel mutation LRG_292t1:c.4356delA,p.(Ala1453Glnfs*3) in the 12th exon ofBRCA1, in the splice site region near the donor site of intron 12. It is a frameshift mutation with the termination codon generated on the third amino acid position from the site of deletion. Human Splice Finder 3.0 and MutationTaster have assessed this variation as disease causing, based on the alteration of splicing, creation of premature stop codon and other potential alterations initiated by nucleotide deletion. Among the most important alterations are frameshift and splice site changes (score of the newly created donor splice site: 0...
Source: Familial Cancer - July 6, 2017 Category: Cancer & Oncology Source Type: research

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