Fred Menko

Fred Menko
Amsterdam University Medical Center | VUmc · Department of Clinical Genetics

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90
Publications
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Publications

Publications (90)
Article
Full-text available
Purpose: Counselees' preferences are considered important for the choice of risk communication format and for improving patient-centered care. We here report on counselees' preferences for how risks are presented in familial breast cancer counseling and the impact of this preferred format on their understanding of risk. Patients and methods: As...
Article
Objective: In hereditary and familial cancer, counselees are requested to inform their at-risk relatives. We developed an intervention to support counselees in this task. Methods: A randomized controlled trial was conducted aimed at improving cancer genetic counselees' i) knowledge, ii) motivation to disclose information, and ii) self-efficacy i...
Article
Context Heterozygous pathogenic germline variants in CDC73 predispose to the development of primary hyperparathyroidism (pHPT), and less frequently, ossifying fibroma of the jaw and renal and uterine tumors. Clinical information on CDC73-related disorders has so far been limited to small case series. Objective To assess the clinical manifestations...
Article
Full-text available
Cancer genetic counselees receive individualized information regarding heightened risks and medical recommendations which is also relevant for their at-risk relatives. Unfortunately, counselees often insufficiently inform these relatives. We designed an intervention aimed at improving counselees' knowledge regarding which at-risk relatives to infor...
Chapter
Renal cell cancer (RCC) is the common denominator for a heterogeneous group of diseases. The subclassification of these tumours is based on histological type and molecular pathogenesis. Insight into molecular pathogenesis has led to the development of targeted systemic therapies. Genetic susceptibility is the principal cause of RCC in about 2–4 % o...
Article
Full-text available
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 surveilla...
Article
Full-text available
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 easi...
Article
Lynch syndrome (LS), a heritable disorder with an increased risk of primarily colorectal cancer (CRC) and endometrial cancer (EC), can be caused by mutations in the PMS2 gene. We wished to establish whether genotype and/or parent-of-origin effects (POE) explain (part of) the reported variability in severity of the phenotype. European PMS2 mutation...
Article
Full-text available
Mutations in fumarate hydratase (FH) on chromosome 1q43 cause a rare cancer syndrome, the hereditary leiomyomatosis and renal cell cancer (HLRCC), but are rare in nonsyndromic and common uterine leiomyoma (UL), or fibroids. Studies suggested that variants in FH or in a linked gene may also predispose to UL. We re-sequenced 2.3 Mb of DNA spanning FH...
Article
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Pneumothorax is classified “spontaneous pneumothorax” if there is no external force causing it and is classified as “primary spontaneous pneumothorax” (PSP) if there is no underlying lung disease. According to the guidelines of the British Thoracic Society (BTS), “no underlying lung disease” is based on history, physical examination and chest radio...
Article
Despite the use of genetic services, counselees do not always share hereditary cancer information with at-risk relatives. Reasons for not informing relatives may be categorized as a lack of: knowledge, motivation, and/or self-efficacy. This study aims to develop and test the psychometric properties of the Informing Relatives Inventory, a battery of...
Article
Full-text available
The clinical consequences of PMS2 germline mutations are poorly understood compared with other Lynch-associated mismatch repair gene (MMR) mutations. The aim of this European cohort study was to define the cancer risk faced by PMS2 mutation carriers. Data were collected from 98 PMS2 families ascertained from family cancer clinics that included a to...
Article
The development and natural course of lung cysts in patients with Birt–Hogg–Dubé syndrome (BHD) is still unclear, and the relationship between lung cysts and pneumothorax is not fully clarified. Based on the follow-up results of thoracic imaging in six patients with BHD, we hypothesize that decreased potential for stretching of the cysts' wall and...
Article
Full-text available
Aim: Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant condition due to germline mutations in the folliculin (FLCN) gene, clinically characterized by skin fibrofolliculomas, lung cysts, (recurrent) spontaneous pneumothorax (SP) and an increased risk of renal cell cancer (RCC). Families with BHD are most often identified through recognition of...
Article
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...
Article
Full-text available
Background Birt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominantly inherited disorder caused by germline mutations in the folliculin (FLCN) gene. Clinical manifestations of BHD include skin fibrofolliculomas, renal cell cancer, lung cysts and (recurrent) spontaneous pneumothorax (SP). All clinical manifestations usually present in adults > 20...
Article
Full-text available
Background: Birt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominant disorder characterised by the occurrence of benign, mostly facial, skin tumours called fibrofolliculomas, multiple lung cysts, spontaneous pneumothorax and an increased renal cancer risk. Current treatments for fibrofolliculomas have high rates of recurrence and carry a risk of...
Article
Lynch syndrome, an autosomal-dominant disorder characterised by high colorectal and endometrial cancer risks, is caused by inherited mutations in DNA mismatch repair (MMR) genes. Mutations fully abrogating gene function are unambiguously disease causing. However, missense mutations often have unknown functional implications, hampering genetic couns...
Article
Full-text available
Background BRCA1 or BRCA2 mutations confer increased risks of breast and ovarian cancer, but risks have been found to vary across studies and populations. Methods We ascertained pedigree data of 582 BRCA1 and 176 BRCA2 families and studied the variation in breast and ovarian cancer risks using a modified segregation analysis model. Results The aver...
Article
Colorectal adenomatous polyposis is associated with a high risk of colorectal cancer (CRC) and is frequently caused by germline mutations in APC or MUTYH. However, in about 20-30% of patients no underlying gene defect can be identified. In this study, we tested if recently identified CRC risk variants play a role in patients with >10 adenomas. We a...
Article
Full-text available
Birt–Hogg–Dubé (BHD) syndrome is an autosomal dominant disorder where patients are predisposed to kidney cancer, lung and kidney cysts and benign skin tumors. BHD is caused by heterozygous mutations affecting folliculin (FLCN), a conserved protein that is considered a tumor suppressor. Previous research has uncovered multiple roles for FLCN in cell...
Article
Many cancer-patients undergo DNA testing in the BRCA1/2 genes to receive information about the likelihood that cancer is heritable. Previous nonsystematic studies suggested that DNA testing often does not fulfill the counselees' needs for certainty. We explored the balance between the counselees' need for certainty and perceived certainty (NfC-PC,...
Article
Full-text available
BACKGROUND: Inadequate understanding of risk among counselees is a common problem in familial cancer clinics. It has been suggested that graphical displays can help counselees understand cancer risks and subsequent decision-making. We evaluated the effects of a graphical presentation in addition to a frequency format on counselees' understanding, p...
Article
Several studies have shown that counselees do not experience psychopathological levels of distress after DNA test result disclosure. However, it has not systematically been studied whether the absence of psychopathology also means that counselees do not want to receive help. Their self-reported request for help may be related not only with psychopa...
Article
The diagnosis of Lynch syndrome can lead to the prevention of colorectal cancer through periodic colonoscopies and removal of premalignant lesions in susceptible individuals. Therefore, predisposed individuals identified by mutation analysis are advised to inform their at-risk relatives about the options of predictive DNA testing and preventive mea...
Article
Full-text available
Recent studies have revealed that BRCA1 and BRCA2 germline mutation-related breast cancers show frequent overexpression of hypoxia inducible factor-1α (HIF-1α), the key regulator of the hypoxia response. However, the question remained whether hypoxia is a late stage bystander or a true carcinogenetic event in patients with hereditary predisposition...
Data
Positive controls: Immunohistochemical staining of HIF-1α and CAIX in renal clear cell carcinoma (B and D) and for Glut-1 in placental tissue (F). In A, C and E the primary antibody was omitted to provide negative controls. (TIF)
Article
Full-text available
Birt–Hogg–Dubé syndrome (BHD) is an autosomal dominant condition due to germline FLCN (folliculin) mutations, characterized by skin fibrofolliculomas, lung cysts, pneumothorax and renal cancer. We identified a de novo FLCN mutation, c.499C>T (p.Gln167X), in a patient who presented with spontaneous pneumothorax. Subsequently, typical skin features a...
Article
Full-text available
PURPOSEPatients with Lynch syndrome are at high risk for colon and endometrial cancer, but also at an elevated risk for other less common cancers. The purpose of this retrospective cohort study was to provide risk estimates for these less common cancers in proven carriers of pathogenic mutations in the mismatch repair (MMR) genes MLH1, MSH2, and MS...
Conference Paper
Purpose: Many women overestimate their risk of breast cancer. Evidence suggests that people fail to adjust their risk perception to account for longer time frames. It has been argued that using narrower time frames (e.g. 10 years) are more appropriate than life time frames. We studied the effects of presenting risk information in age- related 10 ye...
Article
It has been hypothesized that the Outcomes of DNA testing (O) are better predicted and/or mediated by the counselees' Perception P) than by the actually communicated genetic Information (I). In this study, we aimed at quantifying the effect that perception has in genetic counseling for hereditary breast/ovarian cancer. Two hundred and four women, w...
Article
Full-text available
Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant syndrome characterized by skin piloleiomyomas, uterine leiomyomas and papillary type 2 renal cancer caused by germline mutations in the fumarate hydratase (FH) gene. Previously, we proposed renal imaging for FH mutation carriers starting at the age of 20 years. However...
Article
Genetic counseling may help counselees understand their genetic risk of developing breast/ovarian cancer. However, many studies have shown that their perception of their risks is inaccurate. Information-oriented variables often predicted the level of accuracy, focusing on specific processes of receiving and processing risks. We examined counselee-o...
Article
Previously, we proposed that familial multiple trichodiscomas (OMIM 190340) is distinct from Birt-Hogg-Dubé syndrome (BHD) (OMIM #135150). BHD is characterized by multiple fibrofolliculomas/trichodiscomas, lung cysts, pneumothorax, and renal cell cancer. Germline FLCN mutations can be detected in most but not all BHD families. We sought to evaluate...
Article
Previous studies suggest that learning a DNA-test-result has no direct impact on the medical-decisions and psychological well-being of counselees. Their perception, especially their recollections and interpretations of their cancer-risks and heredity, predict and/or mediate this impact. These studies were criticized for their small range of predict...
Article
Full-text available
Objective of this paper is to study how DNA-test result information was communicated and perceived within families. A retrospective descriptive study in 13 probands with a BRCA1/2 unclassified variant, 7 with a pathogenic mutation, 5 with an uninformative result, and in 44, 14, and 12 of their 1st and 2nd degree relatives respectively. We examined...
Article
Background: Unclassified variant and uninformative BRCA1/2 results are not only relevant for probands to whom results are disclosed but also for untested relatives. Previous studies have seldomly included relatives and have not explained how their lives were influenced by these results. We explored the family communication timeline of genetic couns...
Article
Background: Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominantly inherited familial cancer syndrome characterized most commonly by the development of facial fibrofolliculomas, pulmonary cysts (predisposing to spontaneous pneumothorax) and renal cancer. Germline mutations in FLCN on 17p11.2 have been reported in patients with BHD and also in pat...
Article
Full-text available
An unclassified variant (UV) in exon 1 of the MLH1 gene, c.112A > C, p.Asn38His, was found in six families who meet diagnostic criteria for Lynch syndrome. The pathogenicity of this variant was unknown. We aim to elucidate the pathogenicity of this MLH1 variant in order to counsel these families adequately and to enable predictive testing in health...
Data
Table S1. Microsatellite instability- and immunohistochemistry results in patients with MLH1 missense mutation and affected family members.
Article
If a hereditary predisposition to colorectal cancer or breast cancer is diagnosed, most guidelines state that clinical geneticists should request index patients to inform their at-risk relatives about the existence of this condition in their family, thus enabling them to consider presymptomatic genetic testing. Those identified as mutation carriers...
Article
Full-text available
BACKGROUND Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant multisystem disorder with skin (fibrofolliculomas or trichodiscomas), lung (cysts and pneumothorax) and kidney (renal cell carcinoma) tumours. Although colorectal neoplasia was reported initially to be part of the BHD phenotype, some recent studies have not confirmed this association...
Article
BACKGROUND Li-Fraumeni syndrome (LFS) is a rare autosomal dominant cancer predisposition syndrome. Most families fulfilling the classical diagnostic criteria harbour TP53 germline mutations. However, TP53 germline mutations may also occur in less obvious phenotypes. As a result, different criteria are in use to decide which patients qualify for TP5...
Article
Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant condition characterised by the presence of facial fibrofolliculomas, pulmonary cysts which may be associated with spontaneous pneumothorax and renal tumours. Germline mutations in the gene Folliculin (FLCN) were first identified in BHD patients in 2002. In addition FLCN mutations have also been...
Article
Full-text available
Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant condition characterised clinically by skin fibrofolliculomas, pulmonary cysts, spontaneous pneumothorax, and renal cancer. The condition is caused by germline mutations in the FLCN gene, which encodes folliculin; the function of this protein is largely unknown, although FLCN has been linked to...
Article
Spontaneous pneumothorax can be due to Birt-Hogg-Dubé syndrome (BHD syndrome), an autosomal dominant predisposition for fibrofolliculomas, multiple lung cysts, pneumothorax and renal cancer. The syndrome is the result of germline mutations in the FLCN (folliculin) gene. Its clinical presentation is highly variable. Consequently, this syndrome is pr...
Article
Full-text available
Ductal carcinoma in situ (DCIS) is an established late precursor of sporadic invasive breast cancer and to a large extent parallels its invasive counterpart with respect to molecular changes and immunophenotype. Invasive breast cancers in germline BRCA1 and BRCA2 mutation carriers have a distinct "basal" and "luminal" immunophenotype, respectively,...
Article
Full-text available
CHEK2 has previously been excluded as a major cause of Li-Fraumeni syndrome (LFS). One particular CHEK2 germline mutation, c.1100delC, has been shown to be associated with elevated breast cancer risk. The prevalence of CHEK2*1100delC differs between populations and has been found to be relatively high in the Netherlands. The question remains nevert...
Article
Full-text available
Understanding risks is considered to be crucial for informed decision-making. Inaccurate risk perception is a common finding in women with a family history of breast cancer attending genetic counseling. As yet, it is unclear how risks should best be communicated in clinical practice. This study protocol describes the design and methods of the BRISC...
Article
Unclassified variants (UVs, variants of uncertain clinical significance) are found in 13% of all BRCA1/2 mutation analyses. Little is known about the counsellees' recall and interpretation of a UV, and its psychosocial/medical impact. Retrospective semi-structured interviews with open questions and five-point Likert scales were carried out in 24 co...
Article
Full-text available
Birt-Hogg-Dubé syndrome (BHD) is an autosomal-dominant genodermatosis characterized by skin fibrofolliculomas and an increased risk of spontaneous pneumothorax, renal and possibly other tumors. A causative gene (FLCN) on chromosome 17p has recently been identified. We here report clinical and genetic studies of 20 BHD families ascertained by the pr...
Article
Full-text available
Hypoxia is a hallmark of cancer. Hypoxia inducible factor-1alpha (HIF-1alpha) is the key regulator of the hypoxia response. HIF-1alpha is overexpressed during sporadic breast carcinogenesis and correlated with poor prognosis. Little is known on the role of HIF-1alpha in hereditary breast carcinogenesis. A recent study suggests a role for BRCA1 in H...
Article
Background: Heterozygous defects in mismatch-repair (MMR) genes cause hereditary nonpolyposis colorectal cancer (HNPCC). In this syndrome, tumors typically arise from age 25 years onward. Case reports have shown that homozygosity or compound heterozygosity for MMR gene mutations can cause multiple tumors in childhood, sometimes combined with neuro...
Article
Serum CA-125 level is commonly used as indicator for ovarian cancer recurrence. However, its value for the prediction of neoplastic lesions is unknown. The aim of this study was to investigate whether CA-125 concentrations are indicative of adnexal dysplasia and cancer in women at hereditary high risk of ovarian/tubal cancer. CA-125 was obtained fr...
Article
Full-text available
This study examined: (1) levels of cancer-specific distress more than one year after genetic counselling for hereditary nonpolyposis colorectal cancer (HNPCC); (2) associations between sociodemographic, clinical and psychosocial factors and levels of distress; (3) the impact of genetic counselling on family relationships, and (4) social consequence...
Article
To analyse the prevalence of (pre) malignant lesions occurring in breast and adnexal tissue at prophylactic surgery in women at hereditary high risk of breast and/or ovarian cancers. Tissue was obtained from 85 women who underwent prophylactic bilateral salpingo-oophorectomy (pBSO) and from 59 women who underwent prophylactic mastectomy (pM). Contr...
Article
Although an increased cancer risk in Peutz-Jeghers syndrome is established, data on the spectrum of tumors associated with the disease and the influence of germ-line STK11/LKB1 (serine/threonine kinase) mutation status are limited. We analyzed the incidence of cancer in 419 individuals with Peutz-Jeghers syndrome, and 297 had documented STK11/LKB1...
Article
Full-text available
Li-Fraumeni syndrome (LFS) is an autosomal-dominant condition characterized by early-onset sarcoma, breast cancer and other specific tumour types. In most LFS kindreds germline TP53 mutations have been identified. In general, TP53 germline mutations are not associated with late-onset common cancers. We encountered a large kindred in which a wide sp...
Article
Full-text available
Germline mutations of the SDHD, SDHB and SDHC genes, encoding three of the four subunits of succinate dehydrogenase, are a major cause of hereditary paraganglioma and pheochromocytoma, and demonstrate that these genes are classic tumor suppressors. Succinate dehydrogenase is a heterotetrameric protein complex and a component of both the Krebs cycle...
Article
Periodic colonoscopy is an effective means of reducing the incidence and mortality of colorectal cancer in individuals with a family history of the disease. The aims of this study were to determine the degree of compliance and to identify the factors related significantly to noncompliance with periodic screening in this high-risk population. A tota...
Article
Hereditary nonpolyposis colorectal carcinoma (HNPCC) is caused by a mutated mismatch repair (MMR) gene. The aim of our study was to determine the cumulative risk of developing cancer in a large series of MSH6 mutation carriers. Mutation analysis was performed in 20 families with a germline mutation in MSH6. We compared the cancer risks between MSH6...
Article
There is limited data on the spectrum and risk for cancer associated with germline serine/threonine protein kinase 11 (STK11) mutations that cause Peutz-Jeghers syndrome (PJS). We analyzed the incidence of cancer in 240 individuals with PJS possessing germline mutations in STK11. Fifty-four cancers were found among carriers. Overall, the risk for d...
Article
In vitro studies suggest that a deficient mismatch repair (MMR) system reduces 5-Fluorouracil cytotoxicity. Colon cancer (CC) in hereditary nonpolyposis colorectal cancer (HNPCC) is due to a dysfunctioning MMR gene that leads to microsatellite instability (MSI). Clinical studies on the efficacy of 5-Fluorouracil (5-FU) in MSI high tumours are contr...
Article
Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant condition due to heterozygous germline mutations in DNA mismatch repair genes, in particular MLH1, MSH2 and MSH6. Recently, a syndrome was recognized in which children develop haematological malignancies, solid tumours and signs of neurofibromatosis type 1 due to bi-allelic...
Article
The adenoma-carcinoma sequence in hereditary nonpolyposis colorectal cancer (HNPCC) is accelerated. It remains unknown whether the mismatch repair (MMR) defect also promotes the development of adenomas. The aim of this study was to compare the risk of developing colorectal adenoma and carcinoma in HNPCC carriers and noncarriers (controls) and to co...