Hereditary Pancreatic Cancer

Lynch, Henry T.; Brand, Randall E.; Deters, Carolyn A.; Shaw, Trudy G.; Lynch, Jane F.

doi:10.1159/000055849

Cited by 47 publications

(26 citation statements)

References 37 publications

(43 reference statements)

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“…Complementary to these approaches, linkage studies of hereditary cases of pancreatic cancers have localized or identified other genes that play a role in the transformation of pancreatic epithelium (for a review see ref. 5).…”

Section: Introductionmentioning

confidence: 99%

“…5 These cases include pancreatic cancer associated with genetic syndromes such as Peutz-Jeghers syndrome (PJS), familial atypical mole-multiple melanoma syndrome (FAMMM), familial adenomatous polyposis (FAP), hereditary nonpolyposis colon cancer syndrome (HNPCC) and ataxia telangiectasia; familial pancreatic cancer; pancreatic cancer associated with hereditary pancreatitis; and pancreatic carcinoma associated with hereditary breast-ovarian cancer syndrome ( Table 1). The responsible genes for most of these syndromes have been identified, and of these STK11/LKB1, p16INK4, BRCA2, APC, hMSH2 and hMLH1 are known to be altered in some sporadic pancreatic adenocarcinomas.…”

Section: Introductionmentioning

confidence: 99%

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Clinicopathologic and Molecular Features of Pancreatic Adenocarcinoma Associated with Peutz-Jeghers Syndrome

Yee

Furth

Pack

2003

Cancer Biology & Therapy

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Pancreatic cancer is increasingly prevalent and almost uniformly fatal. Studies of the molecular genetics of sporadic and hereditary cases of pancreatic cancer as well as the molecular biology of pancreatic development may advance our understanding of the mechanism underlying pathogenesis of this malignancy. Based on a case of pancreatic adenocarcinoma in a patient with Peutz-Jeghers syndrome (PJS), the clinicopathologic features and molecular genetics of pancreatic tumors associated with this hereditary cancer syndrome are reviewed. Particular emphasis is placed on the developmental roles and biochemical functions of STK11/LKB1, the gene mainly responsible for PJS. Modeling pancreatic cancer in animal models such as the mouse and zebrafish will further our understanding of the pathogenesis of this important disease, and the studies derived from these model organisms can be potentially applied for developing novel preventive and therapeutic strategies.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinicopathologic and Molecular Features of Pancreatic Adenocarcinoma Associated with Peutz-Jeghers Syndrome

Yee

Furth

Pack

2003

Cancer Biology & Therapy

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“…Whether or not an individual who meets both HBOS and FPC criteria has a risk of PC above the increased risk imparted by a BRCA1/2 mutation is unknown. Families highly enriched in PC have been described in several cancer syndromes (Lynch et al 2001(Lynch et al , 2002. At the same time, this finding emphasizes the importance of recognizing the heterogeneity of disease presentation in a given cancer syndrome and the possible clinical implications of that variability (e.g.…”

Section: Discussionmentioning

confidence: 86%

“…While the compilation of family history of breast and ovarian cancer is crucial in an HBOS evaluation, the importance of a family history of PC to cancer risk assessment is less clear. Pancreatic cancer is a manifestation of a number of cancer syndromes, including HBOS (anonymous, 1999;Jagelman et al 1988;Lynch et al 2001;Thompson et al 2002). For known carriers of BRCA1/2 mutations, the relative risk of PC is elevated [BRCA1: RR 2.26 (1.26-4.06); BRCA2: RR 3.51 (1.87-6.58)] though absolute risks are small (anonymous, 1999;Thompson et al 2002).…”

Section: Introductionmentioning

confidence: 99%

Family History of Pancreatic Cancer in a High‐Risk Cancer Clinic: Implications for Risk Assessment

Hall

Dignam²,

Olopade

2008

Journal of Genetic Counseling

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Detailed family history is a critical element of cancer risk assessment. The relative importance of pancreatic cancer (PC) in a close family member, particularly in hereditary breast-ovarian syndrome (HBOS), is not clearly defined. We use a case-control design to investigate the importance of a family history of PC to cancer risk assessment. Case and control families were identified from the University of Chicago Cancer Risk database (1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005). Pedigrees were analyzed for personal and familial clinical cancer data. Cases included all new subjects (probands) reporting a close relative (first or second degree) with PC. Controls included the probands enrolled in the database immediately prior to and subsequent to each case (i.e. two controls for each case). From 1,231 pedigrees, 103 PC were reported by the proband in 87 unique families. Many probands reported multiple or early-onset PCs: one third (28/87) of case families met criteria for a familial PC syndrome [≥2 first-degree relatives with PC (n=10) or PC diagnosed ≤50 (n=18)]. Of these families, the majority (75%) concurrently met criteria suggestive of hereditary breastovarian syndrome (HBOS). Because of a family history consistent with HBOS, at least one individual from each of 29 case and 55 control families underwent genetic testing for BRCA1/2. Among case families, 19 of 29 (66%) had a BRCA1/2 mutation compared with 16 of 55 (29%) controls. A significant association between family history of PC and a BRCA1/2 mutation was seen (OR 3.78,). This point estimate was strengthened but less precise in the nonAshkenazi Jewish subset of tested families (OR 6.03,. In a high-risk population, a family history of PC, though infrequently reported, is nonetheless clinically meaningful. In risk assessment for HBOS, identifying a family history of PC should strongly raise the suspicion of an unrecognized BRCA1/2 mutation.

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“…This exact definition, however, remains a matter of debate (54). Studies of familial aggregation in this population have shown a 2.8-to 18-fold increase in the risk of pancreatic cancer in patients with a positive family history when compared with controls (11, 55 -59), with a risk that tends to increase with the number of affected kindreds.…”

Section: Translational Relevancementioning

confidence: 99%

Screening for Pancreatic Cancer in High-Risk Individuals: A Call for Endoscopic Ultrasound

Larghi

Verna

Lecca

et al. 2009

Clinical Cancer Research

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Pancreatic cancer has a dismal prognosis, and early detection through screening is likely to be our best hope to improve survival. The relatively low incidence of pancreatic cancer and the insensitive screening techniques available currently render this approach prohibitively expensive and inefficient in the general population. Screening has begun, however, in the subset of patients at the highest risk of disease, such as those with inherited risk due to familial multiorgan cancer syndromes or in familial groupings of pancreatic cancer with yet unidentified genetic abnormalities, termed familial pancreatic cancer. Screening is currently done at several large centers in the world, each with a unique multidisciplinary approach and series of screening tests. Endoscopic ultrasound has emerged as the most promising imaging test given its high sensitivity and potential for tissue sampling. However, this potential to detect and cure early lesions should be carefully balanced with the risk of overtreatment, especially in view of the morbidity and mortality of pancreatic surgery. Additional experience to help determine the best screening strategy is greatly needed. Screening should therefore be done at experienced centers with multidisciplinary teams of specialists and in the context of research protocols.

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Hereditary Pancreatic Cancer

Cited by 47 publications

References 37 publications

Clinicopathologic and Molecular Features of Pancreatic Adenocarcinoma Associated with Peutz-Jeghers Syndrome

Clinicopathologic and Molecular Features of Pancreatic Adenocarcinoma Associated with Peutz-Jeghers Syndrome

Family History of Pancreatic Cancer in a High‐Risk Cancer Clinic: Implications for Risk Assessment

Screening for Pancreatic Cancer in High-Risk Individuals: A Call for Endoscopic Ultrasound

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