Hans F A Vasen

Leiden University Medical Centre, Leyden, South Holland, Netherlands

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Publications (371)2545.73 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: 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 total of 2,548 family members and 377 proven mutation carriers. To adjust for potential ascertainment bias, a modified segregation analysis model was used to calculate colorectal cancer (CRC) and endometrial cancer (EC) risks. Standardized incidence ratios (SIRs) were calculated to estimate risks for other Lynch syndrome-associated cancers. The cumulative risk (CR) of CRC for male mutation carriers by age 70 years was 19%. The CR among female carriers was 11% for CRC and 12% for EC. The mean age of CRC development was 52 years, and there was a significant difference in mean age of CRC between the probands (mean, 47 years; range, 26 to 68 years) and other family members with a PMS2 mutation (mean, 58 years; range, 31 to 86 years; P < .001). Significant SIRs were observed for cancers of the small bowel, ovaries, breast, and renal pelvis. CRC and EC risks were found to be markedly lower than those previously reported for the other MMR. However, these risks embody the isolated risk of carrying a PMS2 mutation, and it should be noted that we observed a substantial variation in cancer phenotype within and between families, suggesting the influence of genetic modifiers and lifestyle factors on cancer risks. © 2014 by American Society of Clinical Oncology.
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 12/2014;
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    ABSTRACT: The detection of pancreatic tumors lacks a sensitive and specific diagnostic tool. Mass spectrometry (MS)-based profiling of serum proteins is a promising approach for discovery of new clinical biomarkers or biomarker signatures.
    Journal of Cancer Research and Clinical Oncology 09/2014; · 2.91 Impact Factor
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    ABSTRACT: The p16-Leiden germline variant in the CDKN2A gene is associated with a high risk of melanoma and pancreatic cancer. The aims of this study were to assess the risk of developing other cancers and to determine whether tobacco use would alter cancer risk in carriers of such a variant. We therefore prospectively evaluated individuals with a p16-Leiden germline variant, participating in a pancreatic surveillance programme, for the occurrence of cancer (n=150). Tobacco use was assessed at the start of the surveillance programme. We found a significantly increased risk for melanoma (relative risk (RR) 41.3; 95% confidence interval (CI) 22.9-74.6) and pancreatic cancer (RR 80.8; 95% CI 44.7-146). In addition, increased risks were found for cancers of the lip, mouth and pharynx (RR 18.8; 95% CI 6.05-58.2) and respiratory tumours (RR 4.56; 95% CI 1.71-12.1). Current smokers developed significantly more cancers of the lip, mouth and pharynx, respiratory system and pancreas compared with former and never-smokers. In conclusion, this study shows that carriers of a p16-Leiden variant have an increased risk of developing various types of cancer, and smoking significantly increases the risk of frequently occurring cancers. Smoking cessation should be an integral part of the management of p16-Leiden variant carriers.European Journal of Human Genetics advance online publication, 17 September 2014; doi:10.1038/ejhg.2014.187.
    European journal of human genetics: EJHG 09/2014; · 3.56 Impact Factor
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    ABSTRACT: The aim was to determine the prevalence of small-bowel neoplasia in asymptomatic patients with Lynch syndrome (LS) by video capsule endoscopy (VCE).
    Gastroenterology 09/2014; 144(5):S-25–S-26. · 12.82 Impact Factor
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    ABSTRACT: Background:We aimed to quantify previously observed relatively high cancer risks in BRCA2 mutation carriers (BRCA2 carriers) over 60 in the Northern Netherlands, and to analyze whether these could be explained by mutation spectrum or population background risk. Methods:This consecutive cohort study included all known pathogenic BRCA1/2 carriers in the Northern Netherlands (N = 1,050). Carrier and general reference populations were: BRCA1/2 carriers in the rest of the Netherlands (N = 2,013) and the general population in both regions. Regional differences were assessed with hazard ratios (HRs) and odds ratios (ORs). HRs were adjusted for birth year and mutation spectrum. Results:All BRCA1 carriers and BRCA2 carriers under age 60 had a significantly lower breast cancer risk in the Northern Netherlands, HRs were 0.66 and 0.64, respectively. Above age 60, the breast cancer risk in BRCA2 carriers in the Northern Netherlands was higher than in the rest of the Netherlands (HR = 3.99, 95% CI 1.11-14.35). Adjustment for mutational spectrum changed the HRs for BRCA1, BRCA2 <60 and BRCA2 ≥60 years by -3%, +32% and +11% to 0.75, 0.50 and 2.61, respectively. There was no difference in background breast cancer incidence between the two regions (OR = 1.03, 95% CI 0.97-1.09). Conclusions:Differences in mutation spectrum only partly explain the regional differences in breast cancer risk in BRCA2 carriers, and for an even smaller part in BRCA1 carriers. Impact:The increased risk in BRCA2 carriers over 60 may warrant extension of intensive breast screening beyond age 60.
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    ABSTRACT: Dietary intake of B vitamins and methionine, essential components of DNA synthesis and methylation pathways, may influence colorectal tumor (CRT) development. The impact of B vitamins on colorectal carcinogenesis in individuals with Lynch syndrome (LS) is unknown but is important given their high lifetime risk of developing neoplasms. The role of MTHFR C677T genotype in modifying these relationships in LS individuals is also unclear. We investigated associations between dietary intakes of folate, vitamins B2, B6, B12, and methionine and CRT development in a prospective cohort study of 470 mismatch repair gene mutation carriers.
    Cancer causes & control : CCC. 06/2014;
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    ABSTRACT: Data on survival of BRCA1/2-associated primary breast cancer (PBC) patients who opt for subsequent contralateral risk-reducing mastectomy (CRRM) are scarce and inconsistent. We examined the efficacy of CRRM on overall survival in mutation carriers with a history of PBC. From a Dutch multicentre cohort, we selected 583 BRCA-associated PBC patients, being diagnosed between 1980 and 2011. Over time, 242 patients (42%) underwent CRRM and 341 patients (58%) remained under surveillance. Survival analyses were carried out using Cox models, with CRRM as a time-dependent covariate. The median follow-up after PBC diagnosis was 11.4 years. In the CRRM group, four patients developed contralateral breast cancer (2%), against 64 patients (19%) in the surveillance group (p<0.001). The mortality was lower in the CRRM group than in the surveillance group (9.6 and 21.6 per 1000 person-years of observation, respectively; adjusted hazard ratio 0.49, 95% confidence interval 0.29-0.82). Survival benefit was especially seen in young PBC patients (<40 years), in patients having a PBC with differentiation grade 1/2 and/or no triple-negative phenotype, and in patients not treated with adjuvant chemotherapy. We conclude that CRRM is associated with improved overall survival in BRCA1/2 mutation carriers with a history of PBC. Further research is warranted to develop a model based on age at diagnosis and tumour and treatment characteristics that can predict survival benefit for specific subgroups of patients, aiming at further personalized counselling and improved decision making. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 06/2014; · 6.20 Impact Factor
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    ABSTRACT: Constitutional mismatch repair deficiency (CMMRD) syndrome is a distinct childhood cancer predisposition syndrome that results from biallelic germline mutations in one of the four MMR genes, MLH1, MSH2, MSH6 or PMS2. The tumour spectrum is very broad, including mainly haematological, brain and intestinal tract tumours. Patients show a variety of non-malignant features that are indicative of CMMRD. However, currently no criteria that should entail diagnostic evaluation of CMMRD exist. We present a three-point scoring system for the suspected diagnosis CMMRD in a paediatric/young adult cancer patient. Tumours highly specific for CMMRD syndrome are assigned three points, malignancies overrepresented in CMMRD two points and all other malignancies one point. According to their specificity for CMMRD and their frequency in the general population, additional features are weighted with 1-2 points. They include multiple hyperpigmented and hypopigmented skin areas, brain malformations, pilomatricomas, a second childhood malignancy, a Lynch syndrome (LS)-associated tumour in a relative and parental consanguinity. According to the scoring system, CMMRD should be suspected in any cancer patient who reaches a minimum of three points by adding the points of the malignancy and the additional features. The diagnostic steps to confirm or refute the suspected diagnosis are outlined. We expect that application of the suggested strategy for CMMRD diagnosis will increase the number of patients being identified at the time when they develop their first tumour. This will allow adjustment of the treatment modalities, offering surveillance strategies for second malignancies and appropriate counselling of the entire family.
    Journal of Medical Genetics 04/2014; · 5.70 Impact Factor
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    ABSTRACT: Lynch syndrome (LS) is an autosomal dominant disorder caused by a defect in one of the DNA mismatch repair genes: MLH1, MSH2, MSH6 and PMS2. In the last 15 years, an increasing number of patients have been described with biallelic mismatch repair gene mutations causing a syndrome referred to as 'constitutional mismatch repair-deficiency' (CMMR-D). The spectrum of cancers observed in this syndrome differs from that found in LS, as about half develop brain tumours, around half develop digestive tract cancers and a third develop haematological malignancies. Brain tumours and haematological malignancies are mainly diagnosed in the first decade of life, and colorectal cancer (CRC) and small bowel cancer in the second and third decades of life. Surveillance for CRC in patients with LS is very effective. Therefore, an important question is whether surveillance for the most common CMMR-D-associated cancers will also be effective. Recently, a new European consortium was established with the aim of improving care for patients with CMMR-D. At a workshop of this group held in Paris in June 2013, one of the issues addressed was the development of surveillance guidelines. In 1968, criteria were proposed by WHO that should be met prior to the implementation of screening programmes. These criteria were used to assess surveillance in CMMR-D. The evaluation showed that surveillance for CRC is the only part of the programme that largely complies with the WHO criteria. The values of all other suggested screening protocols are unknown. In particular, it is questionable whether surveillance for haematological malignancies improves the already favourable outcome for patients with these tumours. Based on the available knowledge and the discussions at the workshop, the European consortium proposed a surveillance protocol. Prospective collection of all results of the surveillance is needed to evaluate the effectiveness of the programme.
    Journal of Medical Genetics 02/2014; · 5.70 Impact Factor
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    ABSTRACT: Men with germline breast cancer 1, early onset (BRCA1) or breast cancer 2, early onset (BRCA2) gene mutations have a higher risk of developing prostate cancer (PCa) than noncarriers. IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in BRCA1/2 mutation carriers and controls) is an international consortium of 62 centres in 20 countries evaluating the use of targeted PCa screening in men with BRCA1/2 mutations. To report the first year's screening results for all men at enrolment in the study. We recruited men aged 40-69 yr with germline BRCA1/2 mutations and a control group of men who have tested negative for a pathogenic BRCA1 or BRCA2 mutation known to be present in their families. All men underwent prostate-specific antigen (PSA) testing at enrolment, and those men with PSA >3 ng/ml were offered prostate biopsy. PSA levels, PCa incidence, and tumour characteristics were evaluated. The Fisher exact test was used to compare the number of PCa cases among groups and the differences among disease types. We recruited 2481 men (791 BRCA1 carriers, 531 BRCA1 controls; 731 BRCA2 carriers, 428 BRCA2 controls). A total of 199 men (8%) presented with PSA >3.0 ng/ml, 162 biopsies were performed, and 59 PCas were diagnosed (18 BRCA1 carriers, 10 BRCA1 controls; 24 BRCA2 carriers, 7 BRCA2 controls); 66% of the tumours were classified as intermediate- or high-risk disease. The positive predictive value (PPV) for biopsy using a PSA threshold of 3.0 ng/ml in BRCA2 mutation carriers was 48%-double the PPV reported in population screening studies. A significant difference in detecting intermediate- or high-risk disease was observed in BRCA2 carriers. Ninety-five percent of the men were white, thus the results cannot be generalised to all ethnic groups. The IMPACT screening network will be useful for targeted PCa screening studies in men with germline genetic risk variants as they are discovered. These preliminary results support the use of targeted PSA screening based on BRCA genotype and show that this screening yields a high proportion of aggressive disease. In this report, we demonstrate that germline genetic markers can be used to identify men at higher risk of prostate cancer. Targeting screening at these men resulted in the identification of tumours that were more likely to require treatment.
    European Urology 01/2014; · 10.48 Impact Factor
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    ABSTRACT: 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 analysed a total of 16 SNPs with a reported association with CRC in a cohort of 252 genetically unexplained index patients with >10 colorectal adenomas and 745 controls. In addition, we collected detailed clinical information from index patients and their first-degree relatives (FDRs). We found a statistically significant association with two of the variants tested: rs3802842 (at chromosome 11q23, OR=1.60, 95% CI 1.3 to 2.0) and rs4779584 (at chromosome 15q13, OR=1.50, 95% CI 1.2 to 1.9). The majority of index patients (84%) had between 10 and 100 adenomas and 15% had >100 adenomas. Only two index patients (1%), both with >100 adenomas, had FDRs with polyposis. Forty-one per cent of the index patients had one or more FDRs with CRC. These SNPs are the first common, low-penetrant variants reported to be associated with adenomatous polyposis not caused by a defect in the APC, MUTYH, POLD1 and POLE genes. Even though familial occurrence of polyposis was very rare, CRC was over-represented in FDRs of polyposis patients and, if confirmed, these relatives will therefore benefit from surveillance.
    Journal of Medical Genetics 11/2013; · 5.70 Impact Factor
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    ABSTRACT: Patients with germline PTEN mutations are at high risk of developing benign and malignant tumours. We aimed to evaluate the cumulative risk of several types of cancer and of dysplastic cerebellar gangliocytoma (Lhermitte-Duclos disease, LDD). In addition, genotype-phenotype correlations in PTEN hamartoma tumour syndrome (PHTS) were assessed. Data on patients with PTEN mutations were collected from clinical genetic centres in Western Europe, Australia, and the USA. The cumulative risk of developing cancers of the breast, thyroid, endometrium, skin, kidneys, colorectum, and lungs, and also LDD was calculated by Kaplan-Meier methods. Associations between mutations and cancer were assessed by Chi square means. A total of 180 germline PTEN mutation carriers, 81 males (45 %), from nine countries were included. The cumulative risk of developing any cancer and/or LDD at age 60 was 56 % for males and 87 % for females (p = 0.001). Females had significant higher risks of developing breast cancer, thyroid cancer, and LDD than males. The only genotype-phenotype correlation identified was a lower frequency of thyroid cancer in patients with missense mutations (p = 0.014). In conclusion, PHTS patients, particularly females, have a substantial risk of developing one or more tumours from a broad tumour spectrum. Major genotype-phenotype associations could not be identified.
    Familial Cancer 08/2013; · 1.94 Impact Factor
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    ABSTRACT: Surveillance guidelines for the management of Familial Colorectal Cancer (FCC), a dominant family history of colorectal cancer in which the Polyposis syndromes and Lynch syndrome have been excluded, are not firmly established. The outcome of colonoscopic surveillance is studied using data from six centres. DNA mismatch repair deficiency was excluded by genetic testing. Families were classified as FCC type X if they fulfilled the original Amsterdam criteria (AC) and late onset (LOFCC) if they fulfilled the AC apart from not having a cancer aged under50. The most advanced findings on colonoscopy were analysed. 1585 individuals (median age 47.3, 44% male) from 530 FCC families (349 FCC type X) underwent a total of 4992 colonoscopies with 7904 patient-years of follow-up. Results for FCC type X and LOFCC were very similar. At baseline22 prevalent asymptomatic colorectal cancers were diagnosed, 120 (7.6%) individuals had high-risk adenomas and 225 (14.2%) simple adenomas. 1088 individualshad further colonoscopy (median follow-up of 6.2 years).Of nine individuals diagnosed with cancer. 8 had a previous history of at least one polyp/adenoma. High-risk adenomas were detected in 92 (8.7%) and multiple adenomas were detected in 20 (1.9%) individuals. Both FCC type X and LOFCC have a high prevalence of colorectal cancers and on follow-up develop high-risk adenomas (including multiple adenomas), but infrequent interval cancers. They should be managed similarly with five-yearly colonoscopies undertaken from between 30-40 with more intensive surveillance in individuals developing multiple or high-risk adenomas.
    International Journal of Cancer 07/2013; · 6.20 Impact Factor
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    ABSTRACT: Background: Life time melanoma risk of mutation carriers from families with a germline mutation in the CDKN2A gene is estimated to be 67%. The necessity to include family members in a melanoma surveillance program is widely endorsed, but there is no consensus on which family members should be invited. Methods: In a retrospective follow-up study we investigated the yield of surveillance of first and second degree relatives of melanoma and pancreatic cancer patients from 21 families with the 'p16-Leiden' CDKN2A mutation. Melanoma incidence rates were compared to the general population. Results: 354 first degree relatives and 391 second degree relatives were included. Forty-five first degree relatives and 11 second degree relatives were diagnosed with melanoma. Most (72%) of second degree relatives diagnosed with melanoma, had become a first degree relative prior to diagnosis, due to the occurrence of a melanoma in a parent or sibling. Overall, melanoma incidence rate was 2.1 per 1000 person years (95% CI, 1.2 to 3.8) in family members still being second degree relatives at diagnosis, compared to 9.9 per 1000 person years (95% CI, 7.4 to 13.3) in first degree relatives. The Standardized Morbidity Ratio for melanoma of second degree relatives compared to the general population was 12.9 (95% CI, 7.2 - 23.4). Conclusions: Second degree relatives from families with the p16-Leiden mutation in CDKN2A have a considerably increased melanoma risk compared to the general population. Impact: This study provides justification for the surveillance of second degree relatives from families with a CDKN2A germline mutation.
    Cancer Epidemiology Biomarkers &amp Prevention 07/2013; · 4.56 Impact Factor
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    ABSTRACT: Despite colonoscopic surveillance, Lynch syndrome patients develop colorectal cancer (CRC). Identification of modifiable factors has the potential to improve outcome of surveillance. The aims of this study were to determine (1) characteristics of patients with CRC, (2) endoscopic and histological features of these cancers, and (3) quality of the previous colonoscopy. Approximately 2,200 medical reports from proven and obligate mutation carriers identified at the Dutch Lynch Syndrome Registry and two large hospitals were retrospectively analyzed for the presence of an interval cancer defined as CRC diagnosed within 24 months of previous colonoscopy. Thirty-one interval cancers were detected in 29 patients (median age of 52 [range 35-73]), after a median time of 17 months. All were MLH1 or MSH2 mutation carriers, and 39 % had a previous CRC. In patients without previous surgery for CRC, 84 % was proximally located. Of all interval cancers, 77 % were at local stage (T1-3N0Mx). In three patients (9 %) with an incomplete previous colonoscopy, CRC was located in the unexamined colon. In six of the nine patients with an adenoma during previous colonoscopy, the cancer was detected in the same colonic segment as the previously removed adenoma. Interval cancers were detected in MLH1 and MSH2 mutation carriers, especially in those with a history of previous CRC and between 40 and 60 years. Interval cancer could be related to incompleteness of previous endoscopy and possibly residual adenomatous tissue. Further reduction of the interval cancer risk may be achieved by optimizing endoscopy quality and individualization of surveillance guidelines.
    International Journal of Colorectal Disease 07/2013; · 2.24 Impact Factor
  • Christoph Engel, Hans F A Vasen
    Journal of Clinical Oncology 06/2013; 31(17):2230. · 18.04 Impact Factor
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    ABSTRACT: Lynch syndrome (LS), one of the most frequent forms of hereditary colorectal cancer (CRC), is caused by a defect in one of the mismatch repair (MMR) genes. Carriers of MMR defects have a strongly increased risk of developing CRC and endometrial cancer. Over the last few years, value-based healthcare has been introduced as an approach to the cost-effective delivery of measurable patient value over complete cycles of care. This requires all involved stakeholders to formulate and validate 'patient value' for Lynch syndrome, as well as to identify targets and associated costs. The aim of this study was to develop a value-based care model for Lynch syndrome that can determine patient value and associated costs, and to design a coordinated care pathway from existing guidelines. All specialists in our hospital involved in the management of LS patients evaluated the care delivered to these patients at their department and formulated outcome measures relevant to patient value. Patients were then invited to complete a questionnaire that assessed the importance of these measures on a scale of 1-10. Six high-value outcomes were identified: (1) prevention of cancer or detection of early stage cancer (2) rapid results from MMR gene mutation testing (3) rapid investigation of the colon and uterus (4) no/little pain during colonoscopy and gynaecologic examination/biopsy (5) the offer of psychological help and (6) registration with the Dutch Lynch syndrome registry. A total of 38 (59 %) out of 62 patients completed the questionnaire. The relevance of all outcomes was confirmed by the patients and mean scores varied from 7.2 to 9.9. Patients underscored the relevance of both proper patient education and the efficiency of surveillance during their care cycle. Value-based care delivery for Lynch syndrome includes the implementation of six parameters related to prevention and early detection of cancer, a short cycle time and registration to ensure continuation of care. Estimated costs are 3320 for the first cycle of care ( 3550 including gynaecologic surveillance) and approximately 720 per subsequent annual cycle ( 950 including gynaecologic surveillance).
    Familial Cancer 05/2013; · 1.94 Impact Factor
  • Familial Cancer 05/2013; · 1.94 Impact Factor
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    ABSTRACT: Lynch syndrome (LS) is one of the inherited colorectal cancer (CRC) syndromes and is due to germline mutations in one of the mismatch repair (MMR) genes. Within LS affected-families the expression of the syndrome varies, which suggests that other factors, such as lifestyle factors, have an influence on the LS phenotype. This review gives an overview of studies that assessed the role of lifestyle factors in the development of CRC in LS. Several published studies investigated smoking habits or body fatness (BMI) in relation to colorectal tumours. Those studies fairly consistently suggest that smoking and a high BMI markedly increase the risk of CRC in persons with LS. Other lifestyle factors, such as physical activity, alcohol or diet have not or only scarcely been studied. Lifestyle factors may indeed affect CRC risk in LS. However, more prospective studies with only confirmed MMR gene mutation carriers should be done to further elucidate the role of all lifestyle factors in CRC and in other types of cancer in persons with LS. Information on the role of lifestyle factors in the development of LS-associated cancers may help in establishing lifestyle and dietary recommendations with the ultimate goal of decreasing cancer risk in persons with LS.
    Familial Cancer 05/2013; · 1.94 Impact Factor
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    ABSTRACT: Serrated polyposis syndrome is associated with an increased colorectal cancer risk. Although the underlying genetic cause of the condition is unknown, first-degree relatives of patients with serrated polyposis have an increased risk for colorectal cancer compared with the general population. This suggests an inheritable component. Since other hereditary polyposis syndromes are often associated with an expanded extracolonic tumour spectrum, our aim was to determine the extra colonic cancer risks for patients with serrated polyposis and their first-degree relatives and compare these risks with the general population. Serrated polyposis index patients from 5 medical centres were included. Demographic data concerning age, sex and reported malignancies were ascertained by reviewing medical charts and histopathology reports. Family history was obtained by examining pedigree records from the department of Clinical Genetics. Incidence rates of extracolonic malignancies were compared with the general population through a person-year analysis, adjusted for age and sex. Population-based incidence data were derived from the Eindhoven Cancer Registry. A total of 105 patients with serrated polyposis and 341 first-degree relatives were included. Among the patients with serrated polyposis, 9 extracolonic cancers were observed, compared to 13 expected malignancies in the general population (RR 0.69 95 % CI 0.36-1.33; p = 0.27). Among the first-degree relatives, 44 extracolonic malignancies were observed, compared to 48 expected malignancies (RR 0.92 95 % CI 0.69-1.24; p = 0.60). In this study, the overall incidence of extracolonic malignancies in patients with serrated polyposis and their first-degree relatives was not increased. Large international studies are required to confirm these results.
    Familial Cancer 04/2013; · 1.94 Impact Factor

Publication Stats

16k Citations
2,545.73 Total Impact Points


  • 1989–2014
    • Leiden University Medical Centre
      • • Department of Gastroenterology and Hepatology
      • • Department of Human Genetics
      • • Department of Pathology
      • • Department of Clinical Genetics
      Leyden, South Holland, Netherlands
  • 2013
    • Universitair Medisch Centrum Groningen
      • Department of Gastroenterology and Hepatology
      Groningen, Province of Groningen, Netherlands
    • Isala Klinieken
      • Department of Gastroenterology and Hepatology
      Zwolle, Overijssel, Netherlands
  • 2007–2013
    • Wageningen University
      • Division of Human Nutrition
      Wageningen, Provincie Gelderland, Netherlands
  • 2011
    • John Hunter Hospital
      New Lambton, New South Wales, Australia
  • 1993–2011
    • Copenhagen University Hospital Hvidovre
      Hvidovre, Capital Region, Denmark
  • 2003–2010
    • Erasmus MC
      • • Department of Internal Oncology
      • • Department of Gastroenterology and Hepatology
      • • Department of Clinical Genetics
      Rotterdam, South Holland, Netherlands
  • 1998–2008
    • University of Groningen
      • • Department of Gastroenterology and Hepatology
      • • Department of Medical Genetics
      Groningen, Province of Groningen, Netherlands
  • 1996–2008
    • Radboud University Nijmegen
      • • Department of Gastroenterology and Hepatology
      • • Department of Pathology
      • • Department of Urology
      Nijmegen, Provincie Gelderland, Netherlands
  • 1994–2008
    • Creighton University
      • Department of Preventive Medicine
      Omaha, Nebraska, United States
  • 1997–2004
    • University of Helsinki
      • Department of Medical Genetics
      Helsinki, Province of Southern Finland, Finland
  • 2002
    • Seoul National University
      • Cancer Research Institute
      Seoul, Seoul, South Korea
  • 1990–2002
    • Leiden University
      • Molecular Cell Biology Group
      Leyden, South Holland, Netherlands
  • 2001
    • Erasmus Universiteit Rotterdam
      • Department of Clinical Genetics
      Rotterdam, South Holland, Netherlands
  • 1989–2001
    • University Medical Center Utrecht
      • • Department of Medical Genetics
      • • Department of Endocrinology
      Utrecht, Utrecht, Netherlands
  • 1999–2000
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • Department of Surgery
      Amsterdam, North Holland, Netherlands
    • University of St Andrews
      • School of Biology
      Saint Andrews, SCT, United Kingdom
    • Institute of Genetics and Molecular Medicine
      Edinburgh, Scotland, United Kingdom
    • Imperial College Healthcare NHS Trust
      Londinium, England, United Kingdom
    • The Seoul Institute
      Sŏul, Seoul, South Korea
  • 1998–1999
    • VU University Amsterdam
      • Department of Clinical Genetics
      Amsterdamo, North Holland, Netherlands