Multi-gene panel testing for hereditary cancer susceptibility in a rural Familial Cancer Program
This study explores our Familial Cancer Program’s experience implementing multi-gene panel testing in a largely rural patient population. We conducted a retrospective review of patients undergoing panel testing between May 2011 and August 2015. Our goal was to evaluate factors that might be predictors of identifying variants (pathogenic or uncertain significance) and to assess clinical management changes due to testing. We utilized a structured family history tool to determine the significance of patient’s family histories with respect to identification of genetic variants. A total of 227 patients underwent pan...
Source: Familial Cancer - July 11, 2016 Category: Cancer & Oncology Source Type: research

M üllerian intra-abdominal carcinomatosis in hereditary breast ovarian cancer syndrome: implications for risk-reducing surgery
Abstract More than 40  years ago Lynch et al. described several multigenerational breast cancer family pedigrees which demonstrated autosomal dominant inheritance of a trait(s) that increased risks for both breast and ovarian cancers. Mutation carriers in at least 90 % of these hereditary breast ovarian cancer (HBOC) s yndrome families have been linked to cancer-associated mutations in the genes BRCA1 and BRCA2 . This review focuses on the contributions of Lynch, colleagues and collaborators and pertinent literature, toward defining the HBOC syndrome, the cancer risks that the inherited adverse mutations convey...
Source: Familial Cancer - July 1, 2016 Category: Cancer & Oncology Source Type: research

Undefined familial colorectal cancer and the role of pleiotropism in cancer susceptibility genes
In conclusion, while we identified genes that may be considered interesting candidates as determinants of CRC risk warranting further research, there is currently scant evidence to support a role for genes other than those responsible for established CRC syndromes in the clinical management of familial CRC. (Source: Familial Cancer)
Source: Familial Cancer - June 29, 2016 Category: Cancer & Oncology Source Type: research

A model for patient-direct screening and referral for familial cancer risk
We describe a systematic model for information collection, screening and referral for hereditary cancer risk. Individuals from three different clinical and research populations were screened for hereditary cancer risk using a two-tier process: a 7-item screener followed by review of family history by a genetic counselor and application of published criteria. A total of 869 subjects participated in the study; 769 in this high risk population had increased familial cancer risk based on the screening questionnaire. Of these eligible participants, 500 (65.0 %) provided family histories and 332 (66.4 %) of these were ...
Source: Familial Cancer - June 27, 2016 Category: Cancer & Oncology Source Type: research

Occurrence of renal cell carcinoma and hematologic malignancies (predominantly lymphoid) in individuals and in families
This study evaluates the occurrence of renal cell cancer and hematologic malignancies in individual patients and families, and the occurrence of age-of-onset anticipation among generations. Family history data from our familial patient registry, including more than 700 pedigrees of familial hematologic malignancies, and 700 patients with renal cell cancer, were reviewed. Twenty-six patients with a personal history of both RCC and HM are reported. Seventy four patients with RCC are noted to have 95 family members with HM. Consistent with past reports, there was male predominance among the patients with both diseases (71&nbs...
Source: Familial Cancer - June 22, 2016 Category: Cancer & Oncology Source Type: research

Lynch syndrome in South America: past, present and future
Abstract After decades of unawareness about Lynch syndrome, the medical community in South America is increasingly interested and informed. The visits and support of mentors like H. T. Lynch had been crucial to this awakening. Several countries have at least one registry with skilled personnel in genetic counseling and research. However, this only represents a very restricted resource for the region. According to the GETH, there are 27 hereditary cancer care centers in South America (21 in Brazil, 3 in Argentina, 1 in Uruguay, 1 in Chile and 1 in Peru). These registries differ in fundamental aspects of function, ...
Source: Familial Cancer - June 10, 2016 Category: Cancer & Oncology Source Type: research

An investigation of the factors effecting high-risk individuals’ decision-making about prophylactic total gastrectomy and surveillance for hereditary diffuse gastric cancer (HDGC)
Abstract Hereditary diffuse gastric cancer has an early onset and poor prognosis, therefore, individuals who carry a pathogenic (CDH1) mutation in the E-cadherin gene (CDH1) are offered endoscopic surveillance and advised to undergo prophylactic total gastrectomy (PTG) in their early to mid-twenties. Patients not ready or fit to undergo gastrectomy, or in whom the genetic testing result is unknown or ambiguous, are offered surveillance. Little is known about the factors that influence decisions to undergo or decline PTG, making it difficult to provide optimal support for those facing these decisions. Qualitative i...
Source: Familial Cancer - June 2, 2016 Category: Cancer & Oncology Source Type: research

Introduction to special issue of Familial Cancer
(Source: Familial Cancer)
Source: Familial Cancer - May 30, 2016 Category: Cancer & Oncology Source Type: research

Surgical considerations in FAP-related pouch surgery: Could we do better?
Abstract The ileoanal pouch has become the standard restorative procedure of choice for patients with the classical phenotype in FAP (familial adenomatous polyposis) and also for ulcerative colitis (UC). Whilst we tend to encounter descriptive analyses comparing functional outcome, fertility and quality of life (QOL) between series in literature, there may be an urgent need to discuss the subtle technical modifications that may be pivotal for improving long-term QOL in FAP patients. Our aim is to review the current literature and discuss the aspects of ileal pouch-anal anastomosis that may require specific reevalu...
Source: Familial Cancer - May 19, 2016 Category: Cancer & Oncology Source Type: research

Angelina and Brad effect
(Source: Familial Cancer)
Source: Familial Cancer - May 3, 2016 Category: Cancer & Oncology Source Type: research

Increased incidence of bladder cancer, lymphoid leukaemia, and myeloma in a cohort of Queensland melanoma families
Abstract Familial cancer risk has been proposed as a shared feature of many cancers, and overall susceptibility is influenced by combinations of low to moderate risk polymorphisms, rare high penetrance germline mutations, and modulation of risk by environmental and genetic factors. Clustering of melanoma occurs in approximately 10 % of families, and an over-representation of additional cancers has been noticed in some ‘melanoma’ families. The degree to which other cancers aggregate in families affected by melanoma has not been well defined. Therefore, this study aimed to assess the risk of cancers...
Source: Familial Cancer - April 23, 2016 Category: Cancer & Oncology Source Type: research

Chemoprevention of familial adenomatous polyposis
Abstract Familial adenomatous polyposis (FAP) has always been first and foremost a surgical disease, whose treatment with colectomy has long been known to reduce risk of premature cancer death. The notion of reducing polyp burden and potentially delaying surgical intervention has spawned a host of “chemoprevention” trials. In this paper I selectively review the findings from these studies, highlighting trial design issues and in particular some of the limitations of historical and existing trial endpoint measures. Nonsteroidal anti-inflammatory agents have been the most commonly employed chemopreventiv...
Source: Familial Cancer - April 15, 2016 Category: Cancer & Oncology Source Type: research

Ventricular fibrillation resulting from electrolyte imbalance reveals vipoma in MEN1 syndrome
Abstract Sporadic VIPoma is an exceedingly rare tumor with an annual incidence of 1:10 million people worldwide, yet it is described in approximately 5 % of MEN1 patients. The majority of VIPomas are malignant and radical surgery is the best therapeutic option. A 58-year-old man presented with cardiocirculatory arrest due to ventricular fibrillation. The patient had a 3-month history of epigastric pain with diarrhea. After reanimation, laboratory data revealed severe hypokalemia and hypercalcemia. Further investigations showed hyperparathyroidism, left adrenal adenoma and pituitary microprolactinoma and genet...
Source: Familial Cancer - April 12, 2016 Category: Cancer & Oncology Source Type: research

Familial adenomatous polyposis in pediatrics: natural history, emerging surveillance and management protocols, chemopreventive strategies, and areas of ongoing debate
Abstract Familial adenomatous polyposis (FAP) is a hereditary condition with a near 100 % lifetime risk of colorectal cancer without prophylactic colectomy. Most patients with FAP have a mutation in the adenomatous polyposis coli gene on chromosome 5q22. This condition frequently presents in children with polyps developing most frequently in the second decade of life and surveillance colonoscopy is required starting at age ten. Polyps are found not only in the colon, but in the stomach and duodenum. Knowledge of the natural history of FAP is important as there are several extra-colonic sequelae which also req...
Source: Familial Cancer - April 7, 2016 Category: Cancer & Oncology Source Type: research

Recent discoveries in the molecular genetics of Lynch syndrome
Abstract Lynch syndrome is the inherited predisposition to cancer caused by a germline mutation in a DNA mismatch repair gene. The consequent tumors have a characteristic microsatellite instability (MSI) phenotype. Genomic sequencing of Lynch syndrome-associated colorectal cancers (CRCs) has demonstrated that these tumors have a substantially greater number of mutations than non-MSI CRCs, and that the target mutations driving tumor behavior are also different from what occurs in sporadic tumors. There are multiple non-Lynch syndrome entities that can create clinical confusion with that disease, including the acqui...
Source: Familial Cancer - April 2, 2016 Category: Cancer & Oncology Source Type: research

Non-genetic health professionals’ attitude towards, knowledge of and skills in discussing and ordering genetic testing for hereditary cancer
This study was undertaken to gain insight in their perceptions, attitudes and knowledge. Two publically accessible databases were used to invite NGHPs providing cancer genetic services to complete a questionnaire. The survey assessed: sociodemographic attributes, experience in ordering hereditary cancer genetic testing, attitude, knowledge, perception of communication skills (e.g. information giving, decision-making) and educational needs. Of all respondents (N = 49, response rate 11 %), most have a positive view of their own information giving (mean = 53.91, range 13–65) and decision making ...
Source: Familial Cancer - March 23, 2016 Category: Cancer & Oncology Source Type: research

Are lung cysts in renal cell cancer (RCC) patients an indication for FLCN mutation analysis?
Abstract Renal cell cancer (RCC) represents 2–3 % of all cancers and is the most lethal of the urologic malignancies, in a minority of cases caused by a genetic predisposition. Birt–Hogg–Dubé syndrome (BHD) is one of the hereditary renal cancer syndromes. As the histological subtype and clinical presentation in BHD are highly variable, this syndrome is easily missed. Lung cysts—mainly under the main carina—are reported to be present in over 90 % of all BHD patients and might be an important clue in differentiating between sporadic RCC and BHD associated RCC. We condu...
Source: Familial Cancer - March 23, 2016 Category: Cancer & Oncology Source Type: research

Correlation between the germline methylation status in ERβ promoter and the risk in prostate cancer: a prospective study
Abstract Familial aggregation of cancer may reflect an overall contribution of inherited genes or a shared mechanism for the manipulation of gene function. DNA methylation in the promoter regions is considered to be a mechanism through which tumor suppressor genes are inhibited, which will lead to tumorigenesis and tumor progression. To evaluate the association between the methylation status in the promoter of estrogen receptor (ER) β,possibly a tumor suppressor gene specific for prostate cancer, and the risk in prostate cancer in a Chinese population, a case–control study that included 56 sp...
Source: Familial Cancer - March 23, 2016 Category: Cancer & Oncology Source Type: research

Erratum to: Methylation of the miR-126 gene associated with glioma progression
(Source: Familial Cancer)
Source: Familial Cancer - March 23, 2016 Category: Cancer & Oncology Source Type: research

Hereditary cancer registries improve the care of patients with a genetic predisposition to cancer: contributions from the Dutch Lynch syndrome registry
Abstract The Dutch Hereditary Cancer Registry was established in 1985 with the support of the Ministry of Health (VWS). The aims of the registry are: (1) to promote the identification of families with hereditary cancer, (2) to encourage the participation in surveillance programs of individuals at high risk, (3) to ensure the continuity of lifelong surveillance examinations, and (4) to promote research, in particular the improvement of surveillance protocols. During its early days the registry provided assistance with family investigations and the collection of medical data, and recommended surveillance when a fami...
Source: Familial Cancer - March 14, 2016 Category: Cancer & Oncology Source Type: research

Patient and genetic counselor perceptions of in-person versus telephone genetic counseling for hereditary breast/ovarian cancer
Abstract Telephone genetic counseling (TC) for high-risk women interested in BRCA1/2 testing has been shown to yield positive outcomes comparable to usual care (UC; in-person) genetic counseling. However, little is known about how genetic counselors perceive the delivery of these alternate forms of genetic counseling. As part of a randomized trial of TC versus UC, genetic counselors completed a 5-item genetic counselor process questionnaire (GCQ) assessing key elements of pre-test sessions (information delivery, emotional support, addressing questions and concerns, tailoring of session, and facilitation of decisio...
Source: Familial Cancer - March 11, 2016 Category: Cancer & Oncology Source Type: research

Genetic counseling and cascade genetic testing in Lynch syndrome
Abstract Lynch syndrome is the most common cause of inherited colorectal and endometrial cancers. Individuals with Lynch syndrome have a 10–80 % lifetime risk for colorectal cancer and a 15–60 % lifetime risk for endometrial cancer. Both cancers are preventable through chemoprevention, intensive cancer surveillance, and risk-reducing surgery options. Efforts to identify as many individuals with Lynch syndrome as possible will prevent cancers and save lives. This includes the traditional cancer genetic counseling model whereby individuals with and without cancer are evaluated for a possible Ly...
Source: Familial Cancer - March 11, 2016 Category: Cancer & Oncology Source Type: research

Estimating cumulative risks for breast cancer for carriers of variants in uncommon genes
We present cumulative risks for several under-studied genes and provide generic information that can be extrapolated to data still emerging. (Source: Familial Cancer)
Source: Familial Cancer - March 9, 2016 Category: Cancer & Oncology Source Type: research

CTNNB1 -mutant colorectal carcinomas with immediate invasive growth: a model of interval cancers in Lynch syndrome
Abstract The implementation of regular colonoscopy programs has significantly decreased the mortality associated with colorectal cancer (CRC) in Lynch syndrome patients. However, interval CRCs in Lynch syndrome that remain undetected by colonoscopy still represent a substantial problem in the management of the syndrome. One possible reason of interval cancers could be a non-polypous pathway of cancer development. To examine the possibility of a non-polypous pathway of CRC development in Lynch syndrome, we analyzed the histological appearance of 46 Lynch syndrome-associated CRCs and compared them to 34 sporadic mic...
Source: Familial Cancer - March 9, 2016 Category: Cancer & Oncology Source Type: research

Evaluation of TP53 Pro72Arg and MDM2 SNP285–SNP309 polymorphisms in an Italian cohort of LFS suggestive patients lacking identifiable TP53 germline mutations
Abstract Li-Fraumeni syndrome (LFS) is a rare genetic cancer predisposition disease, partly determined by the presence of a TP53 germline mutation; lacking thereof, in presence of a typical LFS phenotype, defines a wide group of ‘LFS Suggestive’ patients. Alternative LFS susceptibility genes have been investigated without promising results, thus suggesting other genetic determinants involvement in cancer predisposition. Hence, this study explores the single and combined effects of cancer risk, age of onset and cancer type of three single nucleotide polymorphisms (SNPs)—TP53 Pro72Arg, MDM2 SNP285 ...
Source: Familial Cancer - March 8, 2016 Category: Cancer & Oncology Source Type: research

No evidence of increased breast cancer risk for proven noncarriers from BRCA1 and BRCA2 families
Abstract In families screened for mutations in the BRCA1 or BRCA2 genes and found to have a segregating mutation the breast cancer risk for women shown not to carry the family-specific mutation might be at above “average” risk. We assessed the risk of breast cancer in a clinic based cohort of 725 female proven noncarriers in 239 BRCA1 and BRCA2 families compared with birth-matched controls from the Danish Civil Registration System. Prospective analysis showed no significantly increased risk for breast cancer in noncarriers with a hazard ratio of 0.67 [95 % confidence interval (CI) 0.32–1.42,...
Source: Familial Cancer - March 7, 2016 Category: Cancer & Oncology Source Type: research

Decentralized colonoscopic surveillance with high patient compliance prevents hereditary and familial colorectal cancer
This study evaluates the preventive effect for individuals with a family history of CRC of decentralized colonoscopic surveillance with the guidance of a cancer prevention clinic. We performed a population based prospective study of 261 patients with HCRC or FCRC, recorded in the colonoscopic surveillance registry at the Cancer genetics clinic, University Hospital of Umeå, Sweden. Colonoscopic surveillance was conducted every second (HCRC) or fifth (FCRC) year at local hospitals in Northern Sweden. Main outcome measures were findings of high-risk adenomas (HRA) or CRC, and patient compliance to surveillance. Estimati...
Source: Familial Cancer - March 2, 2016 Category: Cancer & Oncology Source Type: research

MEN 2A-related cutaneous lichen amyloidosis: report of three kindred and systematic literature review of clinical, biochemical and molecular characteristics
Abstract Multiple endocrine neoplasia type 2A (MEN2A) may be rarely associated with cutaneous lichen amyloidosis (CLA), a skin lesion located in the interescapular region. Here, we describe 3 MEN2A-related CLA kindred and perform a systematic review (SR) of the literature on clinical, biochemical and molecular characteristics of MEN2A-related CLA patients. Thirty-eight patients with MEN2A-related CLA followed at our institution were evaluated. The median age at MEN2A diagnosis in our cohort was 25 (13–41) years, 68 % were women and all harbored codon 634 RET mutations. The literature search resulte...
Source: Familial Cancer - February 26, 2016 Category: Cancer & Oncology Source Type: research

Evolution of cancer risk assessment and counseling related to psychological, financial and legal implications
Abstract Cancer risk assessment, genetic counseling and genetic testing have experienced advances and changes over the past two decades due to improved technology, legal movements to protect those at an increased risk for cancer due to genetics, as well as advances in detection, prevention and treatment. This brief article will provide a summary of these advances over three eras of cancer genetics: pre-discovery of the more common high impact genes, namely BRCA1/BRCA2 and the mismatch repair genes associated with Lynch syndrome; the time during which the genes were being discovered; and current day. (Source: Familial Cancer)
Source: Familial Cancer - February 26, 2016 Category: Cancer & Oncology Source Type: research

Difference in CXCR4 expression between sporadic and VHL-related hemangioblastoma
Abstract Central nervous system hemangioblastomas occur sporadically and in patients with von Hippel–Lindau (VHL) disease due to a VHL germline mutation. This mutation leads to enhanced transcription of chemokine receptor 4 (CXCR4), its ligand (CXCL12) and vascular endothelial growth factor A (VEGFA). We aimed to determine in VHL-related and sporadic hemangioblastomas CXCR4, CXCL12, and VEGFA protein expression and to correlate this to hemangioblastoma size and expression in normal surrounding tissue. 27 patients with a hemangioblastoma were included for analysis of immunohistochemistry of tissue, MRI and DN...
Source: Familial Cancer - February 26, 2016 Category: Cancer & Oncology Source Type: research

Multiple endocrine neoplasia type 1 syndrome: single centre experience from western India
We report here a case series of MEN1 patients (n = 18) from 14 unrelated families. Retrospective study describing the clinical profile of MEN1 patients from endocrine unit of a tertiary care hospital from western India. Additionally clinical profile of primary hyperparathyroidism (PHPT) in MEN1 patients was compared with that of apparently sporadic PHPT cohort from our centre. Eighteen patients (10 males, 8 females) diagnosed as MEN1 were included. Mean age at diagnosis was 31.5 ± 10.6 years (range 17–54). Incidence of primary hyperparathyroidism (PHPT), pituitary adenoma (PA), and gas...
Source: Familial Cancer - February 23, 2016 Category: Cancer & Oncology Source Type: research

Communicating genetic test results within the family: Is it lost in translation? A survey of relatives in the randomized six-step study
Abstract Genetic testing for cancer susceptibility genes is increasingly being integrated into medical care. Test results help inform risks of the individual being tested as well as family members who could benefit from knowing the results. The responsibility for informing relatives of genetic test results falls on the proband, the first family member being tested. However, there are several challenges associated with sharing genetic test results within families including incomplete understanding of test results, emotional distance among family members, and poor communication skills. In this paper we describe the ...
Source: Familial Cancer - February 20, 2016 Category: Cancer & Oncology Source Type: research

Colonoscopy and chromoscopy in hereditary colorectal cancer syndromes
Abstract With hereditary colorectal cancer prevention studies it is difficult to demonstrate reduced mortality. Large populations are needed with well characterized genetics followed over a long period of time. Those studies do exist for standard white light colonoscopy surveillance in Lynch syndrome, but not for newer technologies including chromoscopy. For these newer technologies adenoma detection rate becomes the stand-in for mortality, and the assumption is made that surveillance efficacy impacts cancer occurrence. Though well-designed and important work exists in this area, the data do not support firm concl...
Source: Familial Cancer - February 18, 2016 Category: Cancer & Oncology Source Type: research

Familial atypical multiple mole melanoma (FAMMM) syndrome: history, genetics, and heterogeneity
Abstract Approximately 5–10 % of cutaneous melanoma occurs in kindreds with a hereditary predisposition. Mutations in the CDKN2A gene are found to occur in approximately 20–40 % of these kindreds. The first historical mention of what is now called the familial atypical multiple mole melanoma syndrome appears to be from 1820, with more reports throughout the 1950s, 1960s, and later years. In 1991, Lynch and Fusaro described an association between familial multiple mole melanoma and pancreatic cancer and work continues to elucidate the syndrome’s genotypic and phenotypic heterogeneity. In...
Source: Familial Cancer - February 18, 2016 Category: Cancer & Oncology Source Type: research

Finding the needle in a haystack: identification of cases of Lynch syndrome with MLH1 epimutation
Abstract Constitutional epimutation of the DNA mismatch repair gene, MLH1, represents a minor cause of Lynch syndrome. MLH1 epimutations are characterized by the soma-wide distribution of methylation of a single allele of the MLH1 promoter accompanied by constitutive allelic loss of transcription. ‘Primary’ MLH1 epimutations, considered pure epigenetic defects, tend to arise de novo in patients without a family history or any apparent genetic mutation. These demonstrate non-Mendelian inheritance. ‘Secondary’ MLH1 epimutations have a genetic basis and have been linked to non-coding genetic a...
Source: Familial Cancer - February 17, 2016 Category: Cancer & Oncology Source Type: research

Colorectal cancer risk variants at 8q23.3 and 11q23.1 are associated with disease phenotype in APC mutation carriers
Abstract Familial adenomatous polyposis (FAP) is a dominantly inherited syndrome caused by germline mutations in the APC gene and characterized by the development of multiple colorectal adenomas and a high risk of developing colorectal cancer (CRC). The severity of polyposis is correlated with the site of the APC mutation. However, there is also phenotypic variability within families with the same underlying APC mutation, suggesting that additional factors influence the severity of polyposis. Genome-wide association studies identified several single nucleotide polymorphisms (SNPs) that are associated with CRC. We ...
Source: Familial Cancer - February 15, 2016 Category: Cancer & Oncology Source Type: research

Müllerian intra-abdominal carcinomatosis in hereditary breast ovarian cancer syndrome: implications for risk-reducing surgery
Abstract More than 40 years ago Lynch et al. described several multigenerational breast cancer family pedigrees which demonstrated autosomal dominant inheritance of a trait(s) that increased risks for both breast and ovarian cancers. Mutation carriers in at least 90 % of these hereditary breast ovarian cancer (HBOC) syndrome families have been linked to cancer-associated mutations in the genes BRCA1 and BRCA2. This review focuses on the contributions of Lynch, colleagues and collaborators and pertinent literature, toward defining the HBOC syndrome, the cancer risks that the inherited adverse mutations co...
Source: Familial Cancer - February 13, 2016 Category: Cancer & Oncology Source Type: research

High microsatellite instability (MSI-H) colorectal carcinoma: a brief review of predictive biomarkers in the era of personalized medicine
Abstract Approximately 15 % of colorectal carcinomas (CRC) display high level microsatellite instability (MSI-H) due to either a germline mutation in one of the genes responsible for DNA mismatch repair (Lynch syndrome, 3 %) or somatic inactivation of the same pathway, most commonly through hypermethylation of the MLH1 gene (sporadic MSI-H, 12 %). Although heterogeneous, MSI-H colorectal carcinomas as a group show some distinct biologic characteristics when compared to CRC with stable or low level microsatellite instability. In the present review we will highlight therapeutically relevant characteri...
Source: Familial Cancer - February 13, 2016 Category: Cancer & Oncology Source Type: research

Hereditary cancer syndromes: utilizing DNA repair deficiency as therapeutic target
Abstract Human cells have numerous repair mechanisms to counteract various insults incurred on the DNA. Any mutation in these repair mechanisms can lead to accumulation of DNA errors and carcinogenesis. This review aims to discuss the therapeutic options in the two most common DNA repair deficient cancer syndromes, namely Lynch syndrome (hereditary non-polyposis colorectal cancer) and breast cancer susceptibility gene (BRCA) associated ovarian and breast cancer. Deficiency in DNA repair mechanisms renders these tumors with increased sensitivity to platinum agents. There has been increasing amount of information on...
Source: Familial Cancer - February 12, 2016 Category: Cancer & Oncology Source Type: research

Update on Lynch syndrome genomics
Abstract Four main DNA mismatch repair (MMR) genes have been identified, MLH1, MSH2, MSH6, and PMS2, which when mutated cause susceptibility to Lynch syndrome (LS). LS is one of the most prevalent hereditary cancer syndromes in man and accounts for 1–3 % of unselected colorectal carcinomas and some 15 % of those with microsatellite instability and/or absent MMR protein. The International Society for Gastrointestinal Hereditary Tumours (InSiGHT) maintains a database for LS-associated mutations since 1996. The database was recently reorganized to efficiently gather published and unpublished data and ...
Source: Familial Cancer - February 12, 2016 Category: Cancer & Oncology Source Type: research

Evaluation of laboratory perspectives on hereditary cancer panels
This study provides healthcare providers information on the laboratory approach to panel testing, highlighting both commonalities and differences in laboratory approaches, and may allow providers to make more informed decisions when ordering hereditary cancer panels. (Source: Familial Cancer)
Source: Familial Cancer - February 11, 2016 Category: Cancer & Oncology Source Type: research

Controversies in the surgery of patients with familial adenomatous polyposis and Lynch syndrome
Abstract Dominantly inherited syndromes of colorectal cancer predisposition are characterized by multifocal neoplasia with an early age of onset. The risk of colorectal cancer is high in affected patients and care of the patients is based on the aims of cancer prevention and cancer cure. At the same time, quality of life should be disturbed as little as possible. Because patients are generally young, the stakes are high. Injudicious decision-making can have unfortunate effects on patients and families. In this article the controversial aspects of surgery in familial adenomatous polyposis and Lynch syndrome are dis...
Source: Familial Cancer - February 11, 2016 Category: Cancer & Oncology Source Type: research

Modeling the dyadic effects of parenting, stress, and coping on parent–child communication in families tested for hereditary breast-ovarian cancer risk
Abstract Genetic testing for BRCA genes, associated with hereditary breast-ovarian cancer risk, is an accepted cancer control strategy. BRCA genetic testing has both medical and psychosocial implications for individuals seeking testing and their family members. However, promoting open and adaptive communication about cancer risk in the family is challenging for parents of minor children. Using prospective data collected from mothers undergoing BRCA genetic testing and their untested co-parents (N = 102 parenting dyads), we examined how maternal and co-parent characteristics independently and conjointly i...
Source: Familial Cancer - February 5, 2016 Category: Cancer & Oncology Source Type: research

Rapid detection of germline mutations for hereditary gastrointestinal polyposis/cancers using HaloPlex target enrichment and high-throughput sequencing technologies
Abstract Genetic testing for hereditary colorectal polyposis/cancers has become increasingly important. Therefore, the development of a timesaving diagnostic platform is indispensable for clinical practice. We designed and validated target enrichment sequencing for 20 genes implicated in familial gastrointestinal polyposis/cancers in 32 cases with previously confirmed mutations using the HaloPlex enrichment system and MiSeq. We demonstrated that HaloPlex captured the targeted regions with a high efficiency (99.66 % for covered target regions, and 99.998 % for breadth of coverage), and MiSeq achieved a hi...
Source: Familial Cancer - February 2, 2016 Category: Cancer & Oncology Source Type: research

Ovarian cancer patients at high risk of BRCA mutation: the constitutional genetic characterization does not change prognosis
We described clinical, pathological and therapeutic features and compared prognosis of BRCA mutation carriers and non-mutated patients. Out of 617 ovarian cancer patients, we identified 104 patients who were considered at high risk of mutation. The 33 mutated patients were more likely to present a personal (33 vs. 10 %, p = 0.003) or a family (42 vs. 24 %, p = 0.06) history of breast/ovarian cancers. BRCA1/2 mutation carriers and wild type patients displayed similar prognosis: median progression–free survival (PFS) of 20.9 versus 37.7 months (p = 0.21); median overall surv...
Source: Familial Cancer - February 1, 2016 Category: Cancer & Oncology Source Type: research

A mutation of the succinate dehydrogenase B gene in a Korean family with paraganglioma
We report a case of germline SDHB mutation. This mutation was a deletion of thymine at nucleotide position 757 in exon 7 of the SDHB gene (c.757delT). (Source: Familial Cancer)
Source: Familial Cancer - February 1, 2016 Category: Cancer & Oncology Source Type: research

BRCA1/BRCA2 founder mutations and cancer risks: impact in the western Danish population
In conclusion, founder mutations in BRCA1 and BRCA2 contribute to up to one-third of the families in western Denmark and among these the BRCA1 c.3319G>T mutation is potentially linked to an increased risk of ovarian cancer. (Source: Familial Cancer)
Source: Familial Cancer - February 1, 2016 Category: Cancer & Oncology Source Type: research

Migrant breast cancer patients and their participation in genetic counseling: results from a registry-based study
Abstract Certain ethnic groups seem to have less access to cancer genetic counseling. Our study was to investigate the participation in cancer genetic counseling among migrant breast cancer patients of Turkish and Moroccan origin. Hospital medical records of Turkish and Moroccan and of a comparative group of non-Turkish/Moroccan newly diagnosed breast cancer patients were studied. All women were diagnosed between 2007 and 2012. Eligibility for genetic counseling was assessed with a checklist. A total of 156 Turkish/Moroccan patients were identified, and 321 patients were assigned to the comparative group. About on...
Source: Familial Cancer - February 1, 2016 Category: Cancer & Oncology Source Type: research

Constitutional MLH1 methylation presenting with colonic polyposis syndrome and not Lynch syndrome
We report the first case of constitutional MLH1 promoter methylation associated with a colonic polyposis syndrome in a 39 year-old man with a family history of colorectal cancer (CRC) and a personal history of 21 polyps identified over 8 years as well as the development of two synchronous CRCs over 16 months who was evaluated for a hereditary cancer syndrome. Immunohistochemistry (IHC) of multiple tumors showed absent MLH1 and PMS2 expression, though germline testing with Sanger sequencing and multiplex ligation-dependent probe amplification of these mismatch repair genes (MMR) genes was negative. A next gen...
Source: Familial Cancer - January 18, 2016 Category: Cancer & Oncology Source Type: research

Exome sequencing identifies potential novel candidate genes in patients with unexplained colorectal adenomatous polyposis
Abstract In up to 30 % of patients with colorectal adenomatous polyposis, no germline mutation in the known genes APC, causing familial adenomatous polyposis, MUTYH, causing MUTYH-associated polyposis, and POLE or POLD1, causing Polymerase-Proofreading-associated polyposis can be identified, although a hereditary etiology is likely. To uncover new causative genes, exome sequencing was performed using DNA from leukocytes and a total of 12 colorectal adenomas from seven unrelated patients with unexplained sporadic adenomatous polyposis. For data analysis and variant filtering, an established bioinformatics pipe...
Source: Familial Cancer - January 16, 2016 Category: Cancer & Oncology Source Type: research