BRCA1 and pancreatic cancer: pedigree findings and their causal relationships

Lynch, Henry T.; Deters, Carolyn A.; Snyder, Carrie; Lynch, Jane F.; Villeneuve, Pierre; Silberstein, Julie; Martin, Holly; Narod, Steven A.; Brand, Randall E.

doi:10.1016/j.cancergencyto.2004.01.032

Cited by 86 publications

(53 citation statements)

References 37 publications

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“…The patient without molecular conWrmation had a brother and son who carried the identical 5382insC mutation; we later conWrmed the presence of the same mutation in this patient when we sequenced his tumor DNA to identify the remaining allele. The age at diagnosis of pancreatic cancer did not diVer signiWcantly between the mutation carriers and sporadic cases; this is similar to the Wndings of other studies (Lynch et al 2005;Hall and Olopade 2005). Though further studies are needed to deWnitively determine if BRCA1 is associated with increased pancreatic cancer risk, current data suggests that the penetrance of BRCA1 mutations for pancreatic cancer is lower than that of BRCA2 (Risch et al 2006).…”

Section: Discussionsupporting

confidence: 75%

“…Both BRCA1 and BRCA2 have important roles in the repair of double-stranded DNA breaks (Gudmundsdottir and Ashworth 2006). A number of anecdotal reports have described pancreatic cancer in association with BRCA1 mutations (Struewing et al 1997;Lynch et al 2005). We previously identiWed 38 individuals from a group of 102 pancreatic cancer patients who were considered to have intermediate/high-risk families, of whom one Ashkenazi Jewish patient screened positive for a deleterious BRCA1 mutation (Lal et al 2000).…”

Section: Discussionmentioning

confidence: 99%

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Germline BRCA1 mutations predispose to pancreatic adenocarcinoma

et al. 2008

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Although the association of germline BRCA2 mutations with pancreatic adenocarcinoma is well established, the role of BRCA1 mutations is less clear. We hypothesized that the loss of heterozygosity at the BRCA1 locus occurs in pancreatic cancers of germline BRCA1 mutation carriers, acting as a "second-hit" event contributing to pancreatic tumorigenesis. Seven germline BRCA1 mutation carriers with pancreatic adenocarcinoma and nine patients with sporadic pancreatic cancer were identified from clinic- and population-based registries. DNA was extracted from paraffin-embedded tumor and nontumor samples. Three polymorphic microsatellite markers for the BRCA1 gene, and an internal control marker on chromosome 16p, were selected to test for the loss of heterozygosity. Tumor DNA demonstrating loss of heterozygosity in BRCA1 mutation carriers was sequenced to identify the retained allele. The loss of heterozygosity rate for the control marker was 20%, an expected baseline frequency. Loss of heterozygosity at the BRCA1 locus was 5/7 (71%) in BRCA1 mutation carriers; tumor DNA was available for sequencing in 4/5 cases, and three demonstrated loss of the wild-type allele. Only 1/9 (11%) sporadic cases demonstrated loss of heterozygosity at the BRCA1 locus. Loss of heterozygosity occurs frequently in pancreatic cancers of germline BRCA1 mutation carriers, with loss of the wild-type allele, and infrequently in sporadic cancer cases. Therefore, BRCA1 germline mutations likely predispose to the development of pancreatic cancer, and individuals with these mutations may be considered for pancreatic cancer-screening programs.

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Germline BRCA1 mutations predispose to pancreatic adenocarcinoma

et al. 2008

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“…59 Finally, a variety of other cancers have been implicated, albeit inconsistently, as part of the BRCA1-related cancer spectrum. 60 The most convincing associations are an increased risk of pancreatic cancer 61 and male breast cancer 62,63 with the cumulative breast cancer risks to age 70 among BRCA1 male mutation carriers being 1.2%. Initial reports of increased colorectal cancer risk have generally not been replicated.…”

Section: Brca1-other Related Cancer Risksmentioning

confidence: 99%

Hereditary breast and ovarian cancer due to mutations in BRCA1 and BRCA2

Petrucelli

Daly

Feldman

2010

Genetics in Medicine

358

255

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“…A family history of PC is another risk factor [7][8][9][10][11][12][13][14][15][16]. Familial PC (FPC), which is defined as the presence of two first-degree relatives (FDRs) with PC and is not associated with known hereditary syndromes, accounts for 4-10% of all PC cases [7] (similar incidences in western countries and Japan [17]) ( Table 1) [17][18][19][20][21][22][23][24][25][26][27][28].…”

Section: Abbreviationsmentioning

confidence: 99%

Familial pancreatic cancer and hereditary syndromes: screening strategy for high-risk individuals

Matsubayashi

2011

J Gastroenterol

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Globally, and almost evenly across nations, a familial disposition can be found in 4-10% of patients with pancreatic cancer (PC). A family history of PC is a risk for this disease and the risk level changes in correlation with the number of affected relatives. Several hereditary syndromes with potential germline mutation also have a high risk for PC; however, little is yet known regarding the genes responsible for familial pancreatic cancer (FPC). Characteristics of FPC cases are similar to those of other familial tumors, including younger onset than in sporadic cases and an ethnic difference (Ashkenazi Jewish > other Caucasian). Other risks resemble those of sporadic cases and include smoking and diabetes mellitus. People with several genetic syndromes, including Peutz-Jeghers syndrome, hereditary pancreatitis, breast-ovarian cancer syndrome, hereditary nonpolyposis colorectal cancer, and familial adenomatous polyposis also have an increased risk of PC. In many countries, but not yet in Japan, screening of these high-risk individuals is now ongoing for the detection of early PC under established familial pancreatic cancer registries. In addition to the ordinary risk factors, such as smoking, diabetes, pancreatitis, cysts, duct ectasia, and intraductal papillary mucinous neoplasm (IPMN), individuals with a family history of PC and hereditary syndromes are expected to be entered into the screening protocol.

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BRCA1 and pancreatic cancer: pedigree findings and their causal relationships

Cited by 86 publications

References 37 publications

Germline BRCA1 mutations predispose to pancreatic adenocarcinoma

Germline BRCA1 mutations predispose to pancreatic adenocarcinoma

Hereditary breast and ovarian cancer due to mutations in BRCA1 and BRCA2

Familial pancreatic cancer and hereditary syndromes: screening strategy for high-risk individuals

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