The risk of developing pancreatic cancer in families with familial atypical multiple mole melanoma (FAMMM) associated with a specific 19 BP deletion of P16 (P16 Leiden)

Vasen, Hans F. A.; Gruis, Nelleke A.; Frants, R.R.; Velden, Pieter A. van der; Hille, E.T.M.; Bergman, Wilma

doi:10.1016/s0016-5085(00)84701-0

Cited by 107 publications

(144 citation statements)

References 14 publications

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“…Association of pancreatic cancer in our study with colon and small intestinal cancers may indicate the presence of HNPCC in some families in the Swedish FamilyCancer Database (Lynch and de la Chapelle, 2003). Inherited mutations of the CDKN2A tumour suppressor gene have been reported in pancreatic cancer patients with a family history of melanoma (Goldstein et al, 1995;Vasen et al, 2000). The BRCA2 gene might also be involved in the observed aggregations of pancreatic cancer with other cancers (for example, breast, prostate).…”

Section: Discussionmentioning

confidence: 54%

Familial association of pancreatic cancer with other malignancies in Swedish families

Hiripi

Bermejo

et al. 2009

Br J Cancer

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BACKGROUND:The aim of this study was to characterise the familial association of pancreatic cancer with other malignancies. METHODS: Relative risks (RRs) of pancreatic cancer according to family history of cancer were calculated using the updated Swedish Family-Cancer Database, which includes over 11.5 million individuals. Estimates were based on Poisson regression. RRs of tumours for individuals with a parental history of pancreatic cancer were also estimated. RESULTS: The risk of pancreatic cancer was elevated in individuals with a parental history of cancers of the liver (RR 1.41; 95% CI 1.10 -1.81), kidney (RR 1.37; 95% CI 1.06 -1.76), lung (RR 1.50; 95% CI 1.27 -1.79) and larynx (RR 1.98; 95% CI 1.19 -3.28). Associations were also found between parental history of pancreatic cancer and cancers of the small intestine, colon, breast, lung, testis and cervix in offspring. There was an increased risk of pancreatic cancer associated with early-onset breast cancer in siblings. CONCLUSION: Pancreatic cancer aggregates in families with several types of cancer. Smoking may contribute to the familial aggregation of pancreatic and lung tumours, and the familial clustering of pancreatic and breast cancer could be partially explained by inherited mutations in the BRCA2 gene.

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Section: Discussionmentioning

confidence: 54%

Familial association of pancreatic cancer with other malignancies in Swedish families

Hiripi

Bermejo

et al. 2009

Br J Cancer

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“…8,14 There are several potential explanations for this difference. A reporting bias could exist (over reporting in pancreatic kindreds or underreporting in melanoma kindreds), and our study is limited by relying on proband report of cancer among relatives.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, there has been a relative deficiency of data to estimate penetrance for known carriers of mutations predisposing to pancreatic cancer, with published data from selected melanoma kindreds. 8,14 Therefore, we performed a study in an unselected series of pancreatic adenocarcinoma patients from the Mayo Clinic Biospecimen Resource for Pancreas Research.…”

Section: Introductionmentioning

confidence: 99%

Prevalence of CDKN2A mutations in pancreatic cancer patients: implications for genetic counseling

et al. 2010

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Germline mutations in CDKN2A have been reported in pancreatic cancer families, but genetic counseling for pancreatic cancer risk has been limited by lack of information on CDKN2A mutation carriers outside of selected pancreatic or melanoma kindreds. Lymphocyte DNA from consecutive, unselected white non-Hispanic patients with pancreatic adenocarcinoma was used to sequence CDKN2A. Frequencies of mutations that alter the coding of p16INK4 or p14ARF were quantified overall and in subgroups. Penetrance and likelihood of carrying mutations by family history were estimated. Among 1537 cases, 9 (0.6%) carried germline mutations in CDKN2A, including three previously unreported mutations. CDKN2A mutation carriers were more likely to have a family history of pancreatic cancer (P¼0.003) or melanoma (P¼0.03), and a personal history of melanoma (P¼0.01). Among cases who reported having a first-degree relative with pancreatic cancer or melanoma, the carrier proportions were 3.3 and 5.3%, respectively. Penetrance for mutation carriers by age 80 was calculated to be 58% for pancreatic cancer (95% confidence interval (CI) 8-86%), and 39% for melanoma (95% CI 0-80). Among cases who ever smoked cigarettes, the risk for pancreatic cancer was higher for carriers compared with non-carriers (HR 25.8, P¼2.1Â10 À13 ), but among nonsmokers, this comparison did not reach statistical significance. Germline mutations in CDKN2A among unselected pancreatic cancer patients are uncommon, although notably penetrant, especially among smokers. Carriers of germline mutations of CDKN2A should be counseled to avoid tobacco use to decrease risk of pancreatic cancer in addition to taking measures to decrease melanoma risk. Keywords: cyclin-dependent kinase inhibitor p16; genes; p16; pancreatic neoplasms INTRODUCTION Pancreatic cancer is associated with very poor survival rates, with long-term survivors limited to those with resected early stage tumors. However, detection of pancreatic cancer at an early stage is challenging, and this mandates identification of high-risk groups to be targeted for prevention and screening intervention.Since first observed by Lynch and Krush in 1968, 1 the incidence of pancreatic cancer has been noted to be increased in many families affected by inherited melanoma syndromes. In genetic analyses of these families, 20-40% of inherited increased melanoma susceptibility can be linked to mutations of the CDKN2A gene (p16/Ink4) located on chromosome 9p21. [2][3][4][5] As a result of the increased incidence of pancreatic cancer in melanoma families with CDKN2A mutations, it was hypothesized that mutations likely also predispose to pancreatic cancer development. 2 Mutations in CDKN2A have subsequently been described in familial pancreatic cancer kindreds, some without melanoma. 3,4 Somatic mutations of CDKN2A are present in up to 95% of pancreatic tumors. 5 These findings provide further support for the premise that CDKN2A mutations have an important role in the development of pancreatic cancer. Clinical findings in mutation carri...

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“…Furthermore, p16-Leiden has been found to be associated with a strongly increased risk, approximately 17%, of developing pancreatic cancer, which is known for its high mortality rate [9].…”

Section: Introductionmentioning

confidence: 99%

Genetic testing in familial melanoma: uptake and implications

et al. 2008

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Objective: We report on the uptake and psychological impact of p16-Leiden genetic testing to contribute to a greater understanding of counseling melanoma families.Methods: Within a defined research setting, genetic counseling and testing were offered to members of p16-Leiden-positive melanoma pedigrees, at risk of carrying a gene defect associated with an increased risk of melanoma and pancreatic cancer.Results: One hundred and eighty-four individuals sought counseling, of which 141 (77%) opted for genetic testing. Uptake of genetic counseling and testing, and psychological motivation was evaluated in 94 (57%) individuals. Higher pre-test risk of carrying the mutation and older age proved significantly predictive for counseling uptake. Age was predictive for test acceptance, whereas fearful test expectancies predicted test decline. Counselees had lower distress levels than those reported in other oncogenetic testing settings.Conclusion: We are the first to report on genetic testing for familial melanoma. Following the first counseling session, we found a relatively high uptake rate for p16-Leiden testing and no clinically worrisome levels of distress.

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The risk of developing pancreatic cancer in families with familial atypical multiple mole melanoma (FAMMM) associated with a specific 19 BP deletion of P16 (P16 Leiden)

Cited by 107 publications

References 14 publications

Familial association of pancreatic cancer with other malignancies in Swedish families

Familial association of pancreatic cancer with other malignancies in Swedish families

Prevalence of CDKN2A mutations in pancreatic cancer patients: implications for genetic counseling

Genetic testing in familial melanoma: uptake and implications

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