Distinct gene expression profiles in ovarian cancer linked to Lynch syndrome
Abstract Ovarian cancer linked to Lynch syndrome represents a rare subset that typically presents at young age as early-stage tumors with an overrepresentation of endometrioid and clear cell histologies. We investigated the molecular profiles of Lynch syndrome-associated and sporadic ovarian cancer with the aim to identify key discriminators and central tumorigenic mechanisms in hereditary ovarian cancer. Global gene expression profiling using whole-genome c-DNA-mediated Annealing, Selection, extension, and Ligation was applied to 48 histopathologically matched Lynch syndrome-associated and sporadic ovarian cance...
Source: Familial Cancer - November 15, 2014 Category: Cancer & Oncology Source Type: research

Cribriform-morular variant of papillary thyroid carcinoma: an indication to screen for occult FAP
Abstract Cribriform-morular variant (CMV) is a rare subtype of papillary thyroid carcinoma (PTC) that is associated with familial adenomatous polyposis (FAP). Given the high likelihood for multi-organ malignancies in FAP patients, this study explores the yield of diagnosing occult FAP among CMV-PTC patients. Institutional database was searched in order to identify patients with pathologically-confirmed CMV-PTC from 2000 to 2012. Medical records were reviewed, and clinical and pathological features were analyzed. Eleven cases of CMV were identified from 6,901 patients with PTC, for a prevalence of 0.16 %. All...
Source: Familial Cancer - November 15, 2014 Category: Cancer & Oncology Source Type: research

A primary care audit of familial risk in patients with a personal history of breast cancer
Abstract Breast cancer is the most common cancer diagnosed in women, both in the UK and worldwide. A small proportion of women are at very high risk of breast cancer, having a particularly strong family history. The National Institute for Health and Clinical Excellence (NICE) has advised that practitioners should not, in most instances, actively seek to identify women with a family history of breast cancer. An audit was undertaken at an urban primary care practice of 15,000 patients, using a paper-based, self-administered questionnaire sent to patients identified with a personal history of breast cancer. The ...
Source: Familial Cancer - November 15, 2014 Category: Cancer & Oncology Source Type: research

Association of interleukin-23 receptor gene polymorphisms with risk of bladder cancer in Chinese
Abstract To assess whether polymorphisms of the interleukin-23 receptor (IL23R) gene are associated with bladder transitional cell carcinoma because chronic inflammation contributes to bladder cancer and the IL23R is known to be critically involved in the carcinogenesis of various malignant tumors. 226 patients with bladder cancer and 270 age-matched controls were involved in the study. Polymerase chain reaction–restriction fragment length polymorphism was used for genotyping. Genotype distribution and allelic frequencies between patients and controls were compared. In all three single nucleotide polymo...
Source: Familial Cancer - November 15, 2014 Category: Cancer & Oncology Source Type: research

Molecular heterogeneity of familial myeloproliferative neoplasms revealed by analysis of the commonly acquired JAK2 , CALR and MPL mutations
Abstract The myeloproliferative neoplasms (MPN) are clonal, hematological malignancies that include polycythemia vera, essential thrombocythemia and primary myelofibrosis. While most cases of MPN are sporadic in nature, a familial pattern of inheritance is well recognised. The phenotype and status of the commonly acquired JAK2 V617F, CALR exon 9 and MPL W515L/K mutations in affected individuals from a consecutive series of ten familial MPN (FMPN) kindred are described. Affected individuals display the classical MPN phenotypes together with one kindred identified suggestive of hereditary thrombocytosis. In affecte...
Source: Familial Cancer - November 15, 2014 Category: Cancer & Oncology Source Type: research

Germline CDKN2A mutations in Brazilian patients of hereditary cutaneous melanoma
Abstract Approximately 10 % of all cutaneous melanoma cases occur in a familial context. The major susceptibility gene for familial melanoma is CDKN2A. In Latin America, genetic studies investigating melanoma predisposition are scarce. The aim of this work was to investigate germline CDKN2A point mutations and genomic rearrangements in a cohort of 59 Brazilian melanoma-prone patients. Screening of CDKN2A alterations was performed by sequencing and multiplex ligation probe amplification. Germline CDKN2A mutations affecting p16INK4a were detected in 8 unrelated probands (13.6 %), including 7 familial...
Source: Familial Cancer - November 15, 2014 Category: Cancer & Oncology Source Type: research

High-resolution melting (HRM) assay for the detection of recurrent BRCA1/BRCA2 germline mutations in Tunisian breast/ovarian cancer families
Abstract Germline deleterious mutations in the BRCA1/BRCA2 genes are associated with an increased risk for the development of breast and ovarian cancer. Given the large size of these genes the detection of such mutations represents a considerable technical challenge. Therefore, the development of cost-effective and rapid methods to identify these mutations became a necessity. High resolution melting analysis (HRM) is a rapid and efficient technique extensively employed as high-throughput mutation scanning method. The purpose of our study was to assess the specificity and sensitivity of HRM for BRCA1 and BRCA2...
Source: Familial Cancer - November 15, 2014 Category: Cancer & Oncology Source Type: research

Phenotype of SDHB mutation carriers in the Netherlands
In conclusion, the two main Dutch SDHB founder mutations do not differ in clinical expression and result in a relatively mild phenotype. Over one-third of SDHB mutation carriers develop HNPGL, with sPGL/PCC in only 15 % and malignancy in only 4 %. (Source: Familial Cancer)
Source: Familial Cancer - November 15, 2014 Category: Cancer & Oncology Source Type: research

Muir–Torre syndrome or phenocopy? The value of the immunohistochemical expression of mismatch repair proteins in sebaceous tumors of immunocompromised patients
Abstract Primary and secondary immunodepressive conditions are associated with an increased incidence of sebaceous tumors. Microsatellite instability (MSI) and lack of expression of mismatch repair (MMR) proteins, typical markers of Muir–Torre/Lynch heredo-familial settings, can be recognized also in immunocompromised patients. We aimed to carry on a systematic examination of clinical, immunohistochemical, biomolecular features of sebaceous tumors arising in immunocompromised and immunocompetent patients between 1986 and 2012. Microsatellite screening, immunohistochemical analysis and genetic testing were p...
Source: Familial Cancer - November 15, 2014 Category: Cancer & Oncology Source Type: research

Association of reduced XRCC2 expression with lymph node metastasis in breast cancer tissues
Abstract The main purpose of this study was to evaluate the association between reduction in XRCC2 gene and involvement of lymph node metastasis in breast cancer. In first part of the study, meta-analysis of 14 published XRCC2 studies was performed to define the role of XRCC2 gene as diagnostic marker and in second part of the study XRCC2 gene expression was observed using real time PCR in study cohort of 100 females (50 breast cancer patients and 50 controls). A statistically significant down regulation of XRCC2 (p 
Source: Familial Cancer - November 15, 2014 Category: Cancer & Oncology Source Type: research

Rapid and cost effective screening of breast and ovarian cancer genes using novel sequence capture method in clinical samples
In this study we present a new method to analyse the risk assessment of women to breast and ovarian cancer. Using Haloplex, a novel sequence capture method combined with next-generation sequencing we were able to perform rapid and cost-effective screening of 16 genes that could be associated with an increased risk of breast and ovarian cancer. The rapid and cost effective analysis of this 16-gene cohort can reveal the genetic background of approximately 30 % of hereditary and familiar cases of breast and ovarian cancers. Thus, it opens up a new and high-throughput approach with fast turnaround time to the genetic diag...
Source: Familial Cancer - November 15, 2014 Category: Cancer & Oncology Source Type: research

The secondary bile acid, deoxycholate accelerates intestinal adenoma–adenocarcinoma sequence in Apc min/+ mice through enhancing Wnt signaling
Abstract Colorectal cancer is one of the leading causes of cancer deaths. It correlates to a high fat diet, which causes an increase of the secondary bile acids including deoxycholate (DOC) in the intestine. We aimed to determine the effects of DOC on intestinal carcinogenesis in Apc min/+ mice, a model of spontaneous intestinal adenomas. Four-week old Apc min/+ mice were treated with 0.2 % DOC in drinking water for 12 weeks. The number and size of tumors were measured, and tissue sections were prepared for the evaluation of intestinal carcinogenesis, cell proliferation, and apopto...
Source: Familial Cancer - November 15, 2014 Category: Cancer & Oncology Source Type: research

Hereditary leiomyomatosis and renal cell cancer (HLRCC): renal cancer risk, surveillance and treatment
Abstract Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant condition in which susceptible individuals are at risk for the development of cutaneous leiomyomas, early onset multiple uterine leiomyomas and an aggressive form of type 2 papillary renal cell cancer. HLRCC is caused by germline mutations in the fumarate hydratase (FH) gene which inactivate the enzyme and alters the function of the tricarboxylic acid (Krebs) cycle. Issues surrounding surveillance and treatment for HLRCC-associated renal cell cancer were considered as part of a recent international symposium on HLRCC. The ma...
Source: Familial Cancer - November 15, 2014 Category: Cancer & Oncology Source Type: research

Population-based genetic risk prediction and stratification for ovarian cancer: views from women at high risk
Abstract There is an opportunity to improve outcomes for ovarian cancer (OC) through advances in risk stratification, early detection and diagnosis. A population-based OC genetic risk prediction and stratification program is being developed. A previous focus group study with individuals from the general population showed support for the proposed program. This qualitative interview study explores the attitudes of women at high risk of OC. Eight women participated in one-on-one, in-depth, semi-structured interviews to explore: experiences of learning of OC risk, risk perceptions, OC knowledge and awareness, and opin...
Source: Familial Cancer - November 13, 2014 Category: Cancer & Oncology Source Type: research

First-Line sunitinib in patients with renal cell carcinoma (RCC) in von Hippel–Lindau (VHL) disease: clinical outcome and patterns of radiological response
Abstract von Hippel–Lindau (VHL) is a rare hereditary condition caused by germline alteration of VHL gene predisposing to renal carcinoma and multiple other tumors. Since acquired dysregulation of VHL-dependent pathways is often present in patients with sporadic RCC treated with the anti-angiogenic drug sunitinib, there is a strong rationale to use the same drug in VHL patients with progressive disease in the kidneys or other sites. Our primary objective was to evaluate the activity of sunitinib in terms of progression-free survival. Secondary objectives: rate of radiological response, patterns of responses ...
Source: Familial Cancer - November 13, 2014 Category: Cancer & Oncology Source Type: research

Health professionals’ evaluation of delivering treatment-focused genetic testing to women newly diagnosed with breast cancer
Abstract Increasingly, women are offered genetic testing shortly after diagnosis of breast cancer to facilitate decision-making about treatment, often referred to as ‘treatment-focused genetic testing’ (TFGT). As understanding the attitudes of health professionals is likely to inform its integration into clinical care we surveyed professionals who participated in our TFGT randomized control study. Thirty-six completed surveys were received (response rate 59 %), 15 (42 %) health professionals classified as genetic and 21 (58 %) as non-genetic. Mainly positive experiences with participatin...
Source: Familial Cancer - November 13, 2014 Category: Cancer & Oncology Source Type: research

Identification of a novel MSH6 germline variant in a family with multiple gastro-intestinal malignancies by next generation sequencing
We describe a kindred with multiple gastrointestinal malignancies where a novel MSH6 germline susceptibility variant was identified by exome sequencing after eluding serial routine testing in multiple affected members. This case fosters discussion of our current understanding of DNA mismatch repair deficiency, the management of Lynch Syndrome, and the emerging role of next generation sequencing in laboratory medicine to identify rare pathogenic germline variants in a comprehensive, unbiased fashion. (Source: Familial Cancer)
Source: Familial Cancer - November 8, 2014 Category: Cancer & Oncology Source Type: research

Estimate of the penetrance of BRCA mutation and the COS software for the assessment of BRCA mutation probability
Abstract We have designed the user-friendly COS software with the intent to improve estimation of the probability of a family carrying a deleterious BRCA gene mutation. The COS software is similar to the widely-used Bayesian-based BRCAPRO software, but it incorporates improved assumptions on cancer incidence in women with and without a deleterious mutation, takes into account relatives up to the fourth degree and allows researchers to consider an hypothetical third gene or a polygenic model of inheritance. Since breast cancer incidence and penetrance increase over generations, we estimated birth-cohort-specific in...
Source: Familial Cancer - November 6, 2014 Category: Cancer & Oncology Source Type: research

Single nucleotide polymorphisms in PDCD6 gene are associated with the development of cervical squamous cell carcinoma
Abstract The programmed cell death 6 (PDCD6), discovered as a proapoptotic calcium-binding protein, has recently been found dysregulated in tumors of various origin and contributed to cancer cell viability. The aim of this study was to determine whether SNPs in PDCD6 are associated with cervical squamous cell carcinoma (CSCC). Polymerase chain reaction-restriction fragment length polymorphism method was used to genotype two tag SNPs (rs3756712 and rs4957014) of PDCD6 in 328 CSCC patients and 541 controls. Significantly increased CSCC risks were found to be associated with T allele of rs3756712 and G allele of ...
Source: Familial Cancer - November 2, 2014 Category: Cancer & Oncology Source Type: research

Vestibular schwannoma in a patient with neurofibromatosis type 1: clinical report and literature review
This report highlights the requirement for ongoing surveillance regarding other manifestations of neurofibromatosis type 2 in such patients, as mosaicism cannot be ruled out. In addition to the NF1 mutation, the NF2 mutation should be considered in such cases if pre-implantation genetic diagnosis in undertaken. (Source: Familial Cancer)
Source: Familial Cancer - November 2, 2014 Category: Cancer & Oncology Source Type: research

The impact of risk-reducing gynaecological surgery in premenopausal women at high risk of endometrial and ovarian cancer due to Lynch syndrome
Abstract Women with Lynch syndrome (LS) have a significantly increased lifetime risk of endometrial cancer (40–60 %) and ovarian cancer (7–12 %). Currently there is little evidence to support the efficacy of screening for the early detection of these cancers. Another option is risk-reducing hysterectomy and/or bilateral salpingo-oophorectomy (BSO). Research on the impact of BSO in premenopausal women with a non-LS associated family history cancer has generally shown that women have a high level of satisfaction about their decision to undergo surgery. However, debilitating menopausal symptoms ...
Source: Familial Cancer - October 24, 2014 Category: Cancer & Oncology Source Type: research

Down-regulation of malignant potential by alpha linolenic acid in human and mouse colon cancer cells
Abstract Omega-3 fatty acids (also called ω-3 fatty acis or n-3 fatty acid) are polyunsaturated fatty acids (PUFAs) with a double bond (C=C) at the third carbon atom from the end of the carbon chain. Numerous test tube and animal studies have shown that omega-3 fatty acids may prevent or inhibit the growth of cancers, suggesting that omega-3 fatty acids are important in cancer physiology. Alpha-linolenic acid (ALA) is one of an essential omega-3 fatty acid and organic compound found in seeds (chia and flaxseed), nuts (notably walnuts), and many common vegetable oils. ALA has also been shown to down-regulate ...
Source: Familial Cancer - October 22, 2014 Category: Cancer & Oncology Source Type: research

Desmoid tumour in familial adenomatous polyposis patients: responses to treatments
Abstract No guidelines for desmoid tumors (DT) management are available and DT have now become the first cause of death in FAP patients who had restorative proctocolectomy. We aimed to assess the results of the different treatments used for DT in Familial Adenomatous Polyposis (FAP) patients. All patients followed for FAP who developed a DT between 1970 and 2010 were collated. We analysed separately the history of DT according to location: mesenteric, parietal or mixed. 79 FAP patients [45 females (56 %); mean age 33.3 ± 12.5] presented 149 DT and were included; 16(20 %) had a DT diagnos...
Source: Familial Cancer - October 15, 2014 Category: Cancer & Oncology Source Type: research

Multiple skin hamartomata: a possible novel clinical presentation of SUFU neoplasia syndrome
We report a 55 year old woman referred for investigation on the basis of skin lesions and a family history of two children from different unions with medulloblastoma. Examination of our patient revealed facial papules (classified as benign folliculosebaceous hamartomatous lesions) and dysmorphology (macrocephaly, hypertelorism and prognathism). She reported her father and her son share the same dermatological features; photographs of the son display hypertelorism. Sequencing in our patient revealed a splice-site mutation in intron 6 of SUFU (c. 756+1G>A), predicted to lead to skipping of exon 6. We suggest that the...
Source: Familial Cancer - October 6, 2014 Category: Cancer & Oncology Source Type: research

Long-term outcomes of risk-reducing surgery in unaffected women at increased familial risk of breast and/or ovarian cancer
This study prospectively investigated long-term psychosocial outcomes for women who opted for risk-reducing mastectomy (RRM) and/or risk-reducing salpingo-oophorectomy (RRSO). Unaffected women from high-risk breast cancer families who had completed baseline questionnaires for an existing study and subsequently underwent RRM and/or RRSO, completed measures of perceived breast and ovarian cancer risk, anxiety, depression, cancer-related anxiety, body image, sexual functioning, menopausal symptoms, use of hormone replacement therapy and decision regret 3 years post-surgery. Outcomes were compared to age- and risk-ma...
Source: Familial Cancer - October 5, 2014 Category: Cancer & Oncology Source Type: research

Mitochondrial membrane potential and reactive oxygen species in cancer stem cells
Abstract Cancer stem cells (CSCs) are believed as the initiators of the occurrence, development and recurrence of malignant tumors. Targeting this unique cell population would provide a less toxic approach than regular chemotherapeutic agents that kill bulk rapid proliferating tumor cells and also normal cells which divide rapidly. To date, major research effort has been aimed at identifying and eradicating CSC population. The metabolism heterogeneity of mitochondria in CSCs shows a big promise for cancer research. Of them, mitochondrial membrane potential (Δψm), reflecting the functional status of the m...
Source: Familial Cancer - September 30, 2014 Category: Cancer & Oncology Source Type: research

Outcomes of genetic evaluation for hereditary cancer syndromes in unaffected individuals
Abstract Genetic testing (GT) for inherited cancer predisposition is most informative when initiated in individuals with cancer, thus standard practice recommends GT start in an affected individual. This strategy can be frustrating for unaffected consultands and providers. Retrospective review of cases was performed to compare outcomes of testing the unaffected consultand and recommending that testing start in an affected relative. Records from cancer-free consultands (N = 101), presenting to the University of Michigan Cancer Genetics Clinic between 6/1/2011 and 12/30/2011 were reviewed. All genetics...
Source: Familial Cancer - September 23, 2014 Category: Cancer & Oncology Source Type: research

Familial and sporadic pancreatic cancer share the same molecular pathogenesis
Abstract Pancreatic ductal adenocarcinoma (PDAC) is nearly uniformly lethal, with a median overall survival in 2014 of only 6 months. The genetic progression of sporadic PDAC (SPC) is well established, with common somatic alterations in KRAS, p16/CDKN2A, TP53, and SMAD4/DPC4. Up to 10 % of all PDAC cases occur in families with two or more affected first-degree relatives (familial pancreatic cancer, FPC), but these cases do not appear to present at an obviously earlier age of onset. This is unusual because most familial cancer syndrome patients present at a substantially younger age than that of correspon...
Source: Familial Cancer - September 21, 2014 Category: Cancer & Oncology Source Type: research

Further evidence for pathogenicity of the TP53 tetramerization domain mutation p.Arg342Pro in Li–Fraumeni syndrome
In conclusion, we provide evidence for the co-segregation of a TP53 tetramerization domain mutation and cancer phenotypes, but also report pre-symptomatic mutation carriers within the family. We review published recommendations for clinical management and surveillance of high-risk members in Li–Fraumeni kindreds. (Source: Familial Cancer)
Source: Familial Cancer - September 17, 2014 Category: Cancer & Oncology Source Type: research

MLH1 promotor hypermethylation does not rule out a diagnosis of Lynch syndrome: a case report
We describe a patient with multiple primary cancers, a deleterious germline MSH6 mutation and somatic MLH1 promotor hypermethylation highlighting the importance of incorporating the clinical history with the genetic evaluation. (Source: Familial Cancer)
Source: Familial Cancer - September 12, 2014 Category: Cancer & Oncology Source Type: research

A polymorphism at miRNA-122-binding site in the IL-1α 3′UTR is associated with risk of epithelial ovarian cancer
Abstract We aimed to investigate the association between rs3783553 polymorphism and susceptibility to epithelial ovarian cancer in a Chinese population and discussed the risk factors associated with survival time. In a case–control study, 301 patients diagnosed with epithelial ovarian cancer and 240 healthy controls were genotyped for rs3783553 polymorphism. Survival time of ovarian cancer patients was explored by Kaplan–Meier analysis and Cox proportional hazards modeling. The distributions of genotype and allele frequencies were significantly different between cases and controls. The variant homozygo...
Source: Familial Cancer - September 7, 2014 Category: Cancer & Oncology Source Type: research

Prevalence of the BLM nonsense mutation, p.Q548X, in ovarian cancer patients from Central and Eastern Europe
Abstract A nonsense mutation, p.Q548X, in the BLM gene has recently been associated with an increased risk for breast cancer. In the present work, we investigated the prevalence of this Slavic founder mutation in 2,561 ovarian cancer cases from Russia, Belarus, Poland, Lithuania or Germany and compared its frequency with 6,205 ethnically matched healthy female controls. The p.Q548X allele was present in nine ovarian cancer patients of Slavic ancestry (0.5 %; including one case with concurrent BRCA1 mutation). The mutation was not significantly more frequent in cases than in controls (Mantel–Haenszel OR ...
Source: Familial Cancer - September 3, 2014 Category: Cancer & Oncology Source Type: research

Genetics of endometrial cancer
Abstract Women who report a history of endometrial cancer in a first-degree relative are at increased risk of endometrial cancer, with a hazard ratio of 1.5 to 2.0. Only a minority of patients with familial endometrial cancer have a recognized cancer syndrome. Lynch syndrome is the most common genetic syndrome associated with endometrial cancer and a marked increased risk of colon cancer. Cowden syndrome is a rare condition resulting from a mutation in the tumor suppressor gene phosphatase and tensin homolog. The risk for endometrial cancer is about five times higher in women with Cowden syndrome than in the gene...
Source: Familial Cancer - September 1, 2014 Category: Cancer & Oncology Source Type: research

Influence of family history on psychosocial distress and perceived need for treatment in prostate cancer survivors
This study investigated the effects of family history of PCa on psychosocial distress and perceived psychosocial treatment need. Data were gathered within the German national research project “Familial Prostate Cancer”. 4.123 PCa survivors who had undergone prostatectomy at least 4 years ago received a questionnaire set. 3.623 of the respondents [68.3 % sporadic, sporadic prostate cancer (SPCa); 31.7 % familial, familial prosate cancer (FPCa)] filled in measures of cancer-specific distress (QSC-R10), depression (PHQ-2), and anxiety (GAD-2). Perceived psychosocial treatment need was assessed using...
Source: Familial Cancer - September 1, 2014 Category: Cancer & Oncology Source Type: research

Nucleotide variants of the cancer predisposing gene CDH1 and the risk of non-syndromic cleft lip with or without cleft palate
Abstract The CDH1 gene plays an important role during carcinogenesis and craniofacial morphogenesis. Germline mutations in this gene have been described in families presenting syndromic diffuse gastric cancer and orofacial clefts. The aim of this study was to evaluate the association between nucleotide variants of CDH1 and the risk of non-syndromic cleft lip with or without cleft palate (NSCL/P). Six single nucleotide polymorphisms (SNPs) of the CDH1 gene (rs16260, rs9929218, rs7186053, rs4783573, rs16958383, and rs1801552) were genotyped using the TaqMan SNP genotyping assays in 250 patients with NSCL/P and 540 ...
Source: Familial Cancer - September 1, 2014 Category: Cancer & Oncology Source Type: research

Novel BRCA1 deleterious mutation (c.1918C>T) in familial breast and ovarian cancer syndrome who share a common ancestry
We report a novel mutation (c.1918C>T) in the exon 11 of the BRCA1 gene that consists of a nonsense mutation that causes a stop codon downstream in the 640 position of the protein. The mutation was present in two Spanish unrelated families and was associated with four breast cancer cases, including two bilateral breast cancer (one of them synchronous). The median age/mean age (range) was 48.5/44.25 years (27–53). This finding led us to perform haplotype analysis in all family carriers. Four highly polymorphic microsatellite markers were used (17-3858, 17-3930, D17S855, D17S1326) to establish whether or not al...
Source: Familial Cancer - September 1, 2014 Category: Cancer & Oncology Source Type: research

A family history questionnaire improves detection of women at risk for hereditary gynecologic cancer: a pilot study
Abstract Pilot study to evaluate whether the use of a standardized questionnaire to document family history of cancer improves identification of women who warrant referral to cancer genetic services (CGS) for increased risk of hereditary cancer, compared to their identification in usual care. Prospective intervention study with historic control group. Gynecology outpatient clinic, Maastricht University Medical Centre, the Netherlands. The prospective intervention group consisted of new outpatients between June 1 and August 1, 2011. The historic control group consisted of new outpatients between May 1, 2009 an...
Source: Familial Cancer - September 1, 2014 Category: Cancer & Oncology Source Type: research

Intronic splicing mutations in PTCH1 cause Gorlin syndrome
Abstract Gorlin syndrome is an autosomal dominant disorder characterized by multiple early-onset basal cell carcinoma, odontogenic keratocysts and skeletal abnormalities. It is caused by heterozygous mutations in the tumour suppressor PTCH1. Routine clinical genetic testing, by Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA) to confirm a clinical diagnosis of Gorlin syndrome, identifies a mutation in 60–90 % of cases. We undertook RNA analysis on lymphocytes from ten individuals diagnosed with Gorlin syndrome, but without known PTCH1 mutations by exonic sequencing or MLPA...
Source: Familial Cancer - September 1, 2014 Category: Cancer & Oncology Source Type: research

Limited diagnostic value of microsatellite instability associated pathology features in colorectal cancer
Abstract To determine the diagnostic test characteristics and inter-observer variation of pathology features for identifying high microsatellite instability (MSI-H) colorectal cancer (CRC). Six pathologists blindly evaluated 177 CRC for the presence of MSI-H associated pathology features. Inter-observer agreement was determined by using Kappa-statistics. In the first random 88/177 cases, mucinous carcinoma, tumor-infiltrating lymphocytes (TIL) and Crohns-like infiltrate (CLI) were the best discriminators between MSI-H and microsatellite stable CRC [OR 5.6 (95 % CI 1.7–19), 5.4 (1.8–17) and 3.5 (1...
Source: Familial Cancer - September 1, 2014 Category: Cancer & Oncology Source Type: research

BRCA1 point mutations in premenopausal breast cancer patients from Central Sudan
We report here 33 BRCA1 point mutations, among which 2 novel missense variants, found in 59 Central Sudanese premenopausal BC patients. The high fractions of mutations with intercontinental and uniquely African distribution (17/33, 51.5 % and 14/33, 42.4 %, respectively) are in agreement with the high genetic diversity expected in an African population. Overall 24/33 variants (72.7 %) resulted neutral; 8/33 of unknown significance (24.3 %, including the 2 novel missense mutations); 1 (3.0 %) overtly deleterious. Notably, in silico studies predict that the novel C-terminal missense variant c.5090G&g...
Source: Familial Cancer - September 1, 2014 Category: Cancer & Oncology Source Type: research

BRCA1 founder mutations compared to ovarian cancer in Belarus
Abstract In Belarus and other Slavic countries, founder mutations in the BRCA1 gene are responsible for a significant proportion of breast cancer cases, but the data on contribution of these mutations to ovarian cancers are limited. To estimate the proportion of ovarian cancers in Belarus, which are dependent on BRCA1 Slavic founder mutations, we sought the presence of three most frequent mutations (BRCA1: 5382insC, C61G and, 4153delA) in 158 consecutive unselected cases of ovarian cancer. One of the three founder mutations was present in 25 of 158 unselected cases of ovarian cancer (15.8 %). We recommend th...
Source: Familial Cancer - September 1, 2014 Category: Cancer & Oncology Source Type: research

Fertility and apparent genetic anticipation in Lynch syndrome
Abstract Genetic anticipation is the phenomenon in which age of onset of an inherited disorder decreases in successive generations. Inconsistent evidence suggests that this occurs in Lynch syndrome. A possible cause for apparent anticipation is fecundity bias, which occurs if the disease adversely affects fertility. The purpose of this study was to determine the effect of age of diagnosis of colorectal cancer (CRC) on lifetime fertility in Lynch syndrome, and whether this can falsely create the appearance of genetic anticipation. A computer model simulated age of diagnosis of CRC in hypothetical Lynch syndrome ca...
Source: Familial Cancer - September 1, 2014 Category: Cancer & Oncology Source Type: research

Duplex value of caveolin-1 in non-small cell lung cancer: a meta analysis
This study is prepared to clarify the prognostic value of Cav-1 in patients with non-small cell lung cancer (NSCLC). All eligible articles from China National Knowledge Infrastructure, Pubmed, Highvire, and Science Direct systems were incorporated into this study. We extracted the patients’ clinical characteristics and survival outcomes and performed a meta-analysis to demonstrate the prognostic role of Cav-1 and the correlations between Cav-1 expression and clinical characteristics. Thirteen articles met the inclusion/exclusion criteria. Cav-1 is deregulated in human lung cancers (NSCLC and small cell lung cancer) c...
Source: Familial Cancer - September 1, 2014 Category: Cancer & Oncology Source Type: research

A survey of the practice patterns of gynecologic oncologists dealing with hereditary cancer patients in Japan
Abstract Hereditary breast and ovarian cancer syndrome (HBOC) is a significant type of familial ovarian cancer. A survey of gynecologic oncologists was conducted in order to characterize the state of care and awareness of information provision for HBOC in Japan and to identify information necessary to enhance HBOC care. All gynecologic oncologists certified by the Japan Society of Gynecologic Oncology (JSGO) as specialists in the treatment of ovarian cancer were included. They were sent a 44-question questionnaire dealing with the background of the respondent, the facilities at the respondent’s medical inst...
Source: Familial Cancer - September 1, 2014 Category: Cancer & Oncology Source Type: research

“Would you test your children without their consent?” and other sticky dilemmas in the field of cancer genetic testing
Abstract Cancer genetic testing is surrounded by myriad ethical, legal, and psychosocial implications which are being revisited as testing expands into an everyday practice and into more complicated areas like whole exome and direct-to-consumer testing. We chose to survey cancer genetic counselors and physicians from a wide range of non-genetics specialties to determine what they would do if faced with the complex decisions associated with cancer genetic testing, how their views compare, and how they align with current guidelines and data. Genetic counselors were significantly more likely than non-genetics physic...
Source: Familial Cancer - September 1, 2014 Category: Cancer & Oncology Source Type: research

Erratum to: Frequency of 5382insC mutation of BRCA1 gene among breast cancer patients: an experience from Eastern India
(Source: Familial Cancer)
Source: Familial Cancer - September 1, 2014 Category: Cancer & Oncology Source Type: research