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Cited by 120Pancreatic and Hepatic Oncology ResearchGenetic factors in colorectal cancerBRCA gene mutations in cancer

Inherited pancreatic cancer syndromes

Open access
Solomon, Sheila, Das, Siddhartha, Brand, Randall, Whitcomb, David C.·2012·The Cancer Journal
DOI 10.1097/ppo.0b013e318278c4a6PMC PMC3565835
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Abstract

Pancreatic cancer remains one of the most challenging of all cancers. Genetic risk factors are believed to play a major role, but other than genes coding for blood group, genetic risks for sporadic cases remain elusive. However, several germline mutations have been identified that lead to hereditary pancreatic cancer, familial pancreatic cancer, and increased risk for pancreatic cancer as part of a familial cancer syndrome. The most important genes with variants increasing risk for pancreatic cancer include BRCA1, BRCA2, PALB2, ATM, CDKN2A, APC, MLH1, MSH2, MSH6, PMS2, PRSS1, and STK11. Recognition of members of high-risk families is important for understanding pancreatic cancer biology, for recommending risk reduction strategies and, in some cases, initiating cancer surveillance programs. Because the best methods for surveillance have not been established, the recommendation to refer at-risk patients to centers with ongoing research programs in pancreatic cancer surveillance is supported.

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  • Several studies show that the probability PDAC development can be further increased by including additional factors such as weight change, ethnicity, and lifestyle factors that are commonly contained in electronic medical records.

    “Of note, several studies show that the probability PDAC development can be further increased by including additional factors such as weight change, ethnicity, and lifestyle factors that are commonly contained in electronic medical records.171–178”

    From Artificial Intelligence and Early Detection of Pancreatic Cancer: 2020 Summative Review (2021) · cites this paper as [171]

    The Hereditary and Familial Pancreatic Cancers section treats ethnicity as relevant to identifying inherited risk, and the CDKN2A and PRSS1 sections associate smoking with pancreatic cancer risk in specific high-risk groups (page numbers unavailable). The paper does not report that adding weight change, ethnicity, and lifestyle factors from electronic medical records improves estimates of PDAC development probability. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • Genomic risk contributes to up to 8% of PDAC cases.

    “Recent studies estimate that genomic risk contributes to up to 8% of PDAC cases,180–184”

    From Artificial Intelligence and Early Detection of Pancreatic Cancer: 2020 Summative Review (2021) · cites this paper as [180]

    The opening passage of “Inherited Pancreatic Cancer Syndromes” (page not provided) says inherited risk factors contribute to at least 5–10% of pancreatic adenocarcinoma cases. This supports the general claim that inherited risk contributes to a share of cases, but not “up to 8%” as an upper limit; the paper says the recognized contribution may rise. (LLM, conf=0.86)

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Research works printed but not linked: 63

  1. [1]Lewis ZK Frost CJ Venne VL Pancreatic cancer surveillance among high-risk populations: knowledge and intent Journal of genetic counseling 18 229 238 2009 19263198
  2. [2]Lillemoe KD Yeo CJ Cameron JL Pancreatic cancer: state-of-the-art care CA: a cancer journal for clinicians 50 241 268 2000 10986966
  3. [3]Brand RE Advances in counselling and surveillance of patients at risk for pancreatic cancer Gut 56 1460 1469 2007 17872573 PMC2000231
  4. [4]Klein AP Evidence for a major gene influencing risk of pancreatic cancer Genetic epidemiology 23 133 149 2002 12214307
  5. [5]Lindor NM Greene MH The concise handbook of family cancer syndromes. Mayo Familial Cancer Program Journal of the National Cancer Institute 90 1039 1071 1998 9672254
  6. [6]Brune KA Importance of age of onset in pancreatic cancer kindreds Journal of the National Cancer Institute 102 119 126 2010 20068195 PMC2808346
  7. [7]Rulyak SJ Risk for the Development of Pancreatic Cancer in Famililal Pancreatic Cancer Kindreds Gastroenterology 124 1292 1299 2003 12730869
  8. [9]Chen S Parmigiani G Meta-analysis of BRCA1 and BRCA2 penetrance Journal of clinical oncology: official journal of the American Society of Clinical Oncology 25 1329 1333 2007 17416853 PMC2267287
  9. [10]Claus EB Schildkraut JM Thompson WD Risch NJ The genetic attributable risk of breast and ovarian cancer Cancer 77 2318 2324 1996 8635102
  10. [11]Pal T BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases Cancer 104 2807 2816 2005 16284991
  11. [12]Risch HA Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer American journal of human genetics 68 700 710 2001 11179017 PMC1274482
  12. [13]Struewing JP The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews The New England journal of medicine 336 1401 1408 1997 9145676
  13. [14]Brose MS Cancer risk estimates for BRCA1 mutation carriers identified in a risk evaluation program Journal of the National Cancer Institute 94 1365 1372 2002 12237282
  14. [15]Beger C Down-regulation of BRCA1 in chronic pancreatitis and sporadic pancreatic adenocarcinoma Clinical cancer research: an official journal of the American Association for Cancer Research 10 3780 3787 2004 15173085
  15. [16]Moran A Risk of cancer other than breast or ovarian in individuals with BRCA1 and BRCA2 mutations Familial cancer 11 235 242 2012 22187320
  16. [17]Axilbund JE Absence of germline BRCA1 mutations in familial pancreatic cancer patients Cancer biology & therapy 8 131 135 2009 19029836 PMC2684337
  17. [18]Wooster R Identification of the breast cancer susceptibility gene BRCA2 Nature 378 789 792 1995 8524414
  18. [19]Sharan SK Embryonic lethality and radiation hypersensitivity mediated by Rad51 in mice lacking Brca2 Nature 386 804 810 1997 9126738
  19. [20]Goggins M Germline BRCA2 gene mutations in patients with apparently sporadic pancreatic carcinomas Cancer research 56 5360 5364 1996 8968085
  20. [21]Murphy KM Evaluation of candidate genes MAP2K4, MADH4, ACVR1B, and BRCA2 in familial pancreatic cancer: deleterious BRCA2 mutations in 17% Cancer research 62 3789 3793 2002 12097290
  21. [22]Cancer risks in BRCA2 mutation carriers The Breast Cancer Linkage Consortium. Journal of the National Cancer Institute 91 1310 1316 1999 10433620
  22. [23]Feldmann G Inactivation of Brca2 cooperates with Trp53(R172H) to induce invasive pancreatic ductal adenocarcinomas in mice: a mouse model of familial pancreatic cancer Cancer biology & therapy 11 959 968 2011 21455033 PMC3127047
  23. [24]Rahman N PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene Nature genetics 39 165 167 2007 17200668 PMC2871593
  24. [26]Casadei S Contribution of inherited mutations in the BRCA2-interacting protein PALB2 to familial breast cancer Cancer research 71 2222 2229 2011 21285249 PMC3059378
  25. [27]Geoffroy-Perez B Cancer risk in heterozygotes for ataxia-telangiectasia International journal of cancer Journal international du cancer 93 288 293 2001 11410879
  26. [28]Sahu RP Batra S Srivastava SK Activation of ATM/Chk1 by curcumin causes cell cycle arrest and apoptosis in human pancreatic cancer cells British journal of cancer 100 1425 1433 2009 19401701 PMC2694438
  27. [32]Vasen HF Risk of developing pancreatic cancer in families with familial atypical multiple mole melanoma associated with a specific 19 deletion of p16 (p16-Leiden) International journal of cancer Journal international du cancer 87 809 811 2000 10956390
  28. [33]McWilliams RR Prevalence of CDKN2A mutations in pancreatic cancer patients: implications for genetic counseling European journal of human genetics: EJHG 19 472 478 2011 21150883 PMC3060321
  29. [34]Petersen GM Slack J Nakamura Y Screening guidelines and premorbid diagnosis of familial adenomatous polyposis using linkage Gastroenterology 100 1658 1664 1991 1673441
  30. [35]Kadmon M Tandara A Herfarth C Duodenal adenomatosis in familial adenomatous polyposis coli. A review of the literature and results from the Heidelberg Polyposis Register International journal of colorectal disease 16 63 75 2001 11355321
  31. [36]Giardiello FM Brensinger JD Petersen GM AGA technical review on hereditary colorectal cancer and genetic testing Gastroenterology 121 198 213 2001 11438509
  32. [37]Barrow E Cumulative lifetime incidence of extracolonic cancers in Lynch syndrome: a report of 121 families with proven mutations Clinical genetics 75 141 149 2009 19215248
  33. [38]Kastrinos F Risk of pancreatic cancer in families with Lynch syndrome JAMA 302 1790 1795 2009 19861671 PMC4091624
  34. [39]Geary J Gene-related cancer spectrum in families with hereditary non-polyposis colorectal cancer (HNPCC) Familial cancer 7 163 172 2008 17939062
  35. [40]Handra-Luca A Couvelard A Degott C Flejou JF Correlation between patterns of DNA mismatch repair hmlh1 and hmsh2 protein expression and progression of dysplasia in intraductal papillary mucinous neoplasms of the pancreas Virchows Archiv: an international journal of pathology 444 235 238 2004 14760534
  36. [41]Arnason T Loss of expression of DNA mismatch repair proteins is rare in pancreatic and small intestinal neuroendocrine tumors Archives of pathology & laboratory medicine 135 1539 1544 2011 22129180
  37. [42]House MG Prognostic value of hMLH1 methylation and microsatellite instability in pancreatic endocrine neoplasms Surgery 134 902 908 discussion 909 2003 14668721
  38. [43]Whitcomb DC Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene Nature genetics 14 141 145 1996 8841182
  39. [44]Amann ST Gates LK Aston CE Pandya A Whitcomb DC Expression and penetrance of the hereditary pancreatitis phenotype in monozygotic twins Gut 48 542 547 2001 11247900 PMC1728254
  40. [45]Rebours V Levy P Ruszniewski P An overview of hereditary pancreatitis Dig Liver Dis 2011 21907651
  41. [46]Whitcomb DC Genetic aspects of pancreatitis Annu Rev Med 61 413 424 2010 20059346
  42. [47]Lowenfels AB Maisonneuve P Whitcomb DC Lerch MM DiMagno EP Cigarette smoking as a risk factor for pancreatic cancer in patients with hereditary pancreatitis JAMA 286 169 170 2001 11448279
  43. [48]Rebours V Mortality rate and risk factors in patients with hereditary pancreatitis: uni- and multidimensional analyses The American journal of gastroenterology 104 2312 2317 2009 19550412
  44. [49]Rhim AD EMT and dissemination precede pancreatic tumor formation Cell 148 349 361 2012 22265420 PMC3266542
  45. [50]Daniluk J An NF-kappaB pathway-mediated positive feedback loop amplifies Ras activity to pathological levels in mice The Journal of clinical investigation 122 1519 1528 2012 22406536 PMC3314459
  46. [51]Ulrich CD II Pancreatic cancer in hereditary pancreatitis – Consensus guidelines for prevention, screening, and treatment Pancreatology 1 416 422 2001 12120218
  47. [52]Sutton JM Total pancreatectomy and islet cell autotransplantation as a means of treating patients with genetically linked pancreatitis Surgery 148 676 685 discussion 685–676 2010 20846557
  48. [53]Giardiello FM Very high risk of cancer in familial Peutz-Jeghers syndrome Gastroenterology 119 1447 1453 2000 11113065
  49. [54]Maheu C Pancreatic cancer risk counselling and screening: impact on perceived risk and psychological functioning Familial cancer 9 617 624 2010 20623197
  50. [55]Klein AP Prospective risk of pancreatic cancer in familial pancreatic cancer kindreds Cancer research 64 2634 2638 2004 15059921
  51. [56]Ghiorzo P Contribution of germline mutations in the BRCA and PALB2 genes to pancreatic cancer in Italy Familial cancer 11 41 47 2012 21989927
  52. [57]Stadler ZK Prevalence of BRCA1 and BRCA2 mutations in Ashkenazi Jewish families with breast and pancreatic cancer Cancer 118 493 499 2012 21598239
  53. [58]Ferrone CR BRCA germline mutations in Jewish patients with pancreatic adenocarcinoma Journal of clinical oncology: official journal of the American Society of Clinical Oncology 27 433 438 2009 19064968 PMC3657622
  54. [60]Ghiorzo P CDKN2A is the main susceptibility gene in Italian pancreatic cancer families Journal of medical genetics 49 164 170 2012 22368299
  55. [62]Moore PS Role of disease-causing genes in sporadic pancreatic endocrine tumors: MEN1 and VHL Genes, chromosomes & cancer 32 177 181 2001 11550286
  56. [63]Park JH Germline mutations of the MEN1 gene in Korean families with multiple endocrine neoplasia type 1 (MEN1) or MEN1-related disorders Clinical genetics 64 48 53 2003 12791038
  57. [64]Ohye H A novel germline mutation of multiple endocrine neoplasia type 1 (MEN1) gene in a Japanese MEN1 patient and her daughter Endocrine journal 46 325 329 1999 10460018
  58. [65]Bartsch D MEN1 gene mutations in 12 MEN1 families and their associated tumors European journal of endocrinology/European Federation of Endocrine Societies 139 416 420 1998 9820618
  59. [66]Gargiulo S Germline MLH1 and MSH2 mutations in Italian pancreatic cancer patients with suspected Lynch syndrome Familial cancer 8 547 553 2009 19728162
  60. [67]Lindor NM Pancreatic cancer and a novel MSH2 germline alteration Pancreas 40 1138 1140 2011 21926548 PMC3425611
  61. [68]Banville N Medullary carcinoma of the pancreas in a man with hereditary nonpolyposis colorectal cancer due to a mutation of the MSH2 mismatch repair gene Human pathology 37 1498 1502 2006 16996571
  62. [70]Tischkowitz MD Analysis of the gene coding for the BRCA2-interacting protein PALB2 in familial and sporadic pancreatic cancer Gastroenterology 137 1183 1186 2009 19635604 PMC3914669
  63. [71]Gorry MC Mutations in the cationic trypsinogen gene are associated with recurrent acute and chronic pancreatitis Gastroenterology 113 1063 1068 1997 9322498

Cited by

Sorted by citations

Authors
Solomon, S., Das, S., Brand, R., & Whitcomb, D. C.
Affiliations
University of Pittsburgh (US)
ORCID
Venue
The Cancer Journal
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2012-11
Volume
18
Issue
6
Pages
485-491
ISSN
1528-9117 (ISSN-L)
DOI
10.1097/ppo.0b013e318278c4a6
PMC
PMC3565835
OpenAlex
W2025262971
Cited by
120
References
8
Citations by year
2026: 2 · 2025: 4 · 2024: 11 · 2023: 13 · 2022: 11 · 2021: 17 · 2020: 12 · 2019: 7 · 2018: 9 · 2017: 7 · 2016: 10 · 2015: 5 · 2014: 8 · 2013: 4
FWCI
0.56
Type
journal article
Language
en
Open access
Locations
  • The Cancer Journal (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Diabetes and Digestive and Kidney Diseases (R13DK096904, R56DK061451)
Topics
  • Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
Keywords
hereditary pancreatic cancer, hereditary cancer, germline mutations, genetic risk factors, BRCA1, BRCA2, PALB2, ATM, CDKN2A, APC, MLH1, MSH2, MSH6, PMS2, PRSS1, STK11, cancer surveillance, risk mitigation, high-risk families
MeSH terms
Animals, Humans, Pancreatic Neoplasms, Genetic Predisposition to Disease, Carcinoma, Pancreatic Ductal

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