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Other Syndromes and Genes Associated with Gastric Cancer Predisposition

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Hereditary Gastric and Breast Cancer Syndrome

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Abstract

Gastric cancer is the fifth most common type of cancer and the fourth leading cause of cancer-related death; nevertheless, genetic predisposition to this malignancy is still widely unexplored.

Besides hereditary diffuse gastric cancer (HDGC), associated with germline CDH1 and CTNNA1 pathogenic variants, other genetic syndromes characterized by high risk to develop gastric cancer have been described, encompassing gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS), associated with germline genetic variants in the APC promoter, and familial intestinal gastric cancer (FIGC), still lacking a clear genetic cause.

Moreover, gastric cancer risk is associated with pathogenic variants in genes involved in DNA mismatch repair, such as MLH1 and MSH2 (Lynch syndrome), apoptosis, including TP53 (Li-Fraumeni syndrome) and double-strand break repair, such as BRCA1/BRCA2 and PALB2 (hereditary breast and ovarian cancer syndrome).

Furthermore, gastric cancer can be a manifestation of gastrointestinal polyposis syndromes, such as those associated with APC (familial adenomatous polyposis), MUTYH (MUTYH-associated polyposis), BMPR1A/SMAD4 (juvenile polyposis syndrome), STK11 (Peutz-Jeghers syndrome), and PTEN (Cowden syndrome) genes.

Recent advances in molecular techniques, such as next-generation sequencing, led to the identification of many new genes involved in the predisposition to gastric cancer, some of which are low or moderate penetrant that predispose to other syndromes.

Consequently, in patients with early onset gastric cancer and/or strong gastric cancer family history, the use of multigene panel testing should be considered in cancer risk assessment, including different surveillance recommendations for each syndrome.

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References

  1. van der Post RS, Vogelaar IP, Carneiro F et al (2015) Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers. J Med Genet 52:361–374. https://doi.org/10.1136/jmedgenet-2015-103094

    Article  CAS  PubMed  Google Scholar 

  2. Guilford P, Hopkins J, Harraway J et al (1998) E-cadherin germline mutations in familial gastric cancer. Nature 392:402–405. https://doi.org/10.1038/32918

    Article  CAS  PubMed  Google Scholar 

  3. Majewski IJ, Kluijt I, Cats A et al (2013) An α-E-catenin (CTNNA1) mutation in hereditary diffuse gastric cancer. J Pathol 229:621–629. https://doi.org/10.1002/path.4152

    Article  CAS  PubMed  Google Scholar 

  4. Weren RDA, van der Post RS, Vogelaar IP et al (2018) Role of germline aberrations affecting CTNNA1, MAP3K6 and MYD88 in gastric cancer susceptibility. J Med Genet 55:669–674. https://doi.org/10.1136/jmedgenet-2017-104962

    Article  CAS  PubMed  Google Scholar 

  5. Lobo S, Benusiglio PR, Coulet F et al (2021) Cancer predisposition and germline CTNNA1 variants. Eur J Med Genet 64:104316. https://doi.org/10.1016/j.ejmg.2021.104316

    Article  CAS  PubMed  Google Scholar 

  6. Gaston D, Hansford S, Oliveira C et al (2014) Germline mutations in MAP3K6 are associated with familial gastric cancer. PLoS Genet 10:e1004669. https://doi.org/10.1371/journal.pgen.1004669

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Vogelaar IP, Ligtenberg MJL, van der Post RS et al (2016) Recurrent candidiasis and early-onset gastric cancer in a patient with a genetically defined partial MYD88 defect. Familial Cancer 15:289–296. https://doi.org/10.1007/s10689-015-9859-z

    Article  CAS  PubMed  Google Scholar 

  8. Hansford S, Kaurah P, Li-Chang H et al (2015) Hereditary diffuse gastric cancer syndrome: CDH1 mutations and beyond. JAMA Oncol 1:23–32. https://doi.org/10.1001/jamaoncol.2014.168

    Article  PubMed  Google Scholar 

  9. Vogelaar IP, van der Post RS, van Krieken JHJ et al (2017) Unraveling genetic predisposition to familial or early onset gastric cancer using germline whole-exome sequencing. Eur J Hum Genet 25:1246–1252. https://doi.org/10.1038/ejhg.2017.138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Sahasrabudhe R, Lott P, Bohorquez M et al (2017) Germline mutations in PALB2, BRCA1, and RAD51C, which regulate DNA recombination repair, in patients with gastric cancer. Gastroenterology 152:983–986.e6. https://doi.org/10.1053/j.gastro.2016.12.010

    Article  CAS  PubMed  Google Scholar 

  11. Garcia-Pelaez J, Barbosa-Matos R, São José C et al (2022) Gastric cancer genetic predisposition and clinical presentations: established heritable causes and potential candidate genes. Eur J Med Genet 65:104401. https://doi.org/10.1016/j.ejmg.2021.104401

    Article  CAS  PubMed  Google Scholar 

  12. Slavin T, Neuhausen SL, Rybak C et al (2017) Genetic gastric cancer susceptibility in the international clinical cancer genomics community research network. Cancer Genet 216–217:111–119. https://doi.org/10.1016/j.cancergen.2017.08.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Tedaldi G, Pirini F, Tebaldi M et al (2019) Multigene panel testing increases the number of loci associated with gastric cancer predisposition. Cancers (Basel) 11. https://doi.org/10.3390/cancers11091340

  14. Fewings E, Larionov A, Redman J et al (2018) Germline pathogenic variants in PALB2 and other cancer-predisposing genes in families with hereditary diffuse gastric cancer without CDH1 mutation: a whole-exome sequencing study. Lancet Gastroenterol Hepatol 3:489–498. https://doi.org/10.1016/S2468-1253(18)30079-7

    Article  PubMed  PubMed Central  Google Scholar 

  15. Antoniou AC, Casadei S, Heikkinen T et al (2014) Breast-cancer risk in families with mutations in PALB2. N Engl J Med 371:497–506. https://doi.org/10.1056/NEJMoa1400382

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Helgason H, Rafnar T, Olafsdottir HS et al (2015) Loss-of-function variants in ATM confer risk of gastric cancer. Nat Genet 47:906–910. https://doi.org/10.1038/ng.3342

    Article  CAS  PubMed  Google Scholar 

  17. Moslemi M, Moradi Y, Dehghanbanadaki H et al (2021) The association between ATM variants and risk of breast cancer: a systematic review and meta-analysis. BMC Cancer 21:27. https://doi.org/10.1186/s12885-020-07749-6

    Article  PubMed  PubMed Central  Google Scholar 

  18. Worthley DL, Phillips KD, Wayte N et al (2012) Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS): a new autosomal dominant syndrome. Gut 61:774–779. https://doi.org/10.1136/gutjnl-2011-300348

    Article  CAS  PubMed  Google Scholar 

  19. Carvalho J, Oliveira P, Senz J et al (2020) Redefinition of familial intestinal gastric cancer: clinical and genetic perspectives. J Med Genet 58:1. https://doi.org/10.1136/jmedgenet-2019-106346

    Article  CAS  PubMed  Google Scholar 

  20. Cheng L, Eng C, Nieman LZ et al (2011) Trends in colorectal cancer incidence by anatomic site and disease stage in the United States from 1976 to 2005. Am J Clin Oncol 34:573–580. https://doi.org/10.1097/COC.0b013e3181fe41ed

    Article  PubMed  Google Scholar 

  21. Siegel RL, Medhanie GA, Fedewa SA, Jemal A (2019) State variation in early-onset colorectal cancer in the United States, 1995-2015. J Natl Cancer Inst 111:1104–1106. https://doi.org/10.1093/jnci/djz098

    Article  PubMed  PubMed Central  Google Scholar 

  22. Giardiello FM, Offerhaus JG Phenotype and cancer risk of various polyposis syndromes. Eur J Cancer 31A:1085–7. https://doi.org/10.1016/0959-8049(95)00139-a

  23. Møller P, Seppälä TT, Bernstein I et al (2018) Cancer risk and survival in path_MMR carriers by gene and gender up to 75 years of age: a report from the prospective Lynch syndrome database. Gut 67:1306–1316. https://doi.org/10.1136/gutjnl-2017-314057

    Article  PubMed  Google Scholar 

  24. National Comprehensive Cancer Network (NCCN) (2022) Genetic/Familial High-Risk Assessment: Colorectal v 2.2021. https://www.nccn.org/professionals/physician_gls/pdf/genetics_colon.pdf

  25. Siegel RL, Miller KD, Fuchs HE, Jemal A (2022) Cancer statistics, 2022. CA Cancer J Clin 72:7–33. https://doi.org/10.3322/caac.21708

    Article  PubMed  Google Scholar 

  26. Bailey CE, Hu C-Y, You YN et al (2015) Increasing disparities in the age-related incidences of colon and rectal cancers in the United States, 1975-2010. JAMA Surg 150:17–22. https://doi.org/10.1001/jamasurg.2014.1756

    Article  PubMed  PubMed Central  Google Scholar 

  27. Rumilla K, Schowalter KV, Lindor NM et al (2011) Frequency of deletions of EPCAM (TACSTD1) in MSH2-associated Lynch syndrome cases. J Mol Diagn 13:93–99. https://doi.org/10.1016/j.jmoldx.2010.11.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Masciari S, Dewanwala A, Stoffel EM et al (2011) Gastric cancer in individuals with Li-Fraumeni syndrome. Genet Med 13:651–657. https://doi.org/10.1097/GIM.0b013e31821628b6

    Article  PubMed  PubMed Central  Google Scholar 

  29. National Comprehensive Cancer Network (NCCN) (2022) Genetic/familial high-risk assessment: breast, ovarian, and pancreatic v. 2.2022. https://www.nccn.org/professionals/physician_gls/pdf/genetics_bop.pdf

  30. Friedenson B (2005) BRCA1 and BRCA2 pathways and the risk of cancers other than breast or ovarian. MedGenMed 7:60

    PubMed  PubMed Central  Google Scholar 

  31. Shibata C, Ogawa H, Miura K et al (2013) Clinical characteristics of gastric cancer in patients with familial adenomatous polyposis. Tohoku J Exp Med 229:143–146. https://doi.org/10.1620/tjem.229.143

    Article  PubMed  Google Scholar 

  32. Win AK, Reece JC, Dowty JG et al (2016) Risk of extracolonic cancers for people with biallelic and monoallelic mutations in MUTYH. Int J Cancer 139:1557–1563. https://doi.org/10.1002/ijc.30197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Hearle N, Schumacher V, Menko FH et al (2006) Frequency and spectrum of cancers in the Peutz-Jeghers syndrome. Clin Cancer Res 12:3209–3215. https://doi.org/10.1158/1078-0432.CCR-06-0083

    Article  CAS  PubMed  Google Scholar 

  34. Syngal S, Brand RE, Church JM et al (2015) ACG clinical guideline: genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol 110:223–262. https://doi.org/10.1038/ajg.2014.435

    Article  PubMed  PubMed Central  Google Scholar 

  35. Correia TF, Mesquita I, Marcos M, et al (2021) Surgical approach to gastric polyposis in Cowen syndrome-case report. J Surg Case Rep 2021:rjab258. https://doi.org/10.1093/jscr/rjab258

  36. Rudloff U (2018) Gastric adenocarcinoma and proximal polyposis of the stomach: diagnosis and clinical perspectives. Clin Exp Gastroenterol 11:447–459. https://doi.org/10.2147/CEG.S163227

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Gullo I, van der Post RS, Carneiro F (2021) Recent advances in the pathology of heritable gastric cancer syndromes. Histopathology 78:125–147. https://doi.org/10.1111/his.14228

    Article  PubMed  Google Scholar 

  38. Li J, Woods SL, Healey S et al (2016) Point mutations in exon 1B of APC reveal gastric adenocarcinoma and proximal polyposis of the stomach as a familial adenomatous polyposis variant. Am J Hum Genet 98:830–842. https://doi.org/10.1016/j.ajhg.2016.03.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Beer A, Streubel B, Asari R et al (2017) Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) - a rare recently described gastric polyposis syndrome - report of a case. Z Gastroenterol 55:1131–1134. https://doi.org/10.1055/s-0043-117182

    Article  PubMed  Google Scholar 

  40. Foretová L, Navrátilová M, Svoboda M et al (2019) GAPPS - gastric adenocarcinoma and proximal polyposis of the stomach syndrome in 8 families tested at Masaryk Memorial Cancer Institute - prevention and prophylactic gastrectomies. Klin Onkol 32:109–117. https://doi.org/10.14735/amko2019S109

    Article  PubMed  Google Scholar 

  41. Kanemitsu K, Iwatsuki M, Yamashita K et al (2021) Two Asian families with gastric adenocarcinoma and proximal polyposis of the stomach successfully treated via laparoscopic total gastrectomy. Clin J Gastroenterol 14:92–97. https://doi.org/10.1007/s12328-020-01290-6

    Article  PubMed  Google Scholar 

  42. Mitsui Y, Yokoyama R, Fujimoto S et al (2018) First report of an Asian family with gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) revealed with the germline mutation of the APC exon 1B promoter region. Gastric Cancer 21:1058–1063. https://doi.org/10.1007/s10120-018-0855-5

    Article  CAS  PubMed  Google Scholar 

  43. Repak R, Kohoutova D, Podhola M et al (2016) The first European family with gastric adenocarcinoma and proximal polyposis of the stomach: case report and review of the literature. Gastrointest Endosc 84:718–725. https://doi.org/10.1016/j.gie.2016.06.023

    Article  PubMed  Google Scholar 

  44. Caldas C, Carneiro F, Lynch HT et al (1999) Familial gastric cancer: overview and guidelines for management. J Med Genet 36:873–880

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Oliveira C, Suriano G, Ferreira P et al (2004) Genetic screening for familial gastric cancer. Hered Cancer Clin Pract 2:51–64. https://doi.org/10.1186/1897-4287-2-2-51

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Shinmura K, Kohno T, Takahashi M et al (1999) Familial gastric cancer: clinicopathological characteristics, RER phenotype and germline p53 and E-cadherin mutations. Carcinogenesis 20:1127–1131. https://doi.org/10.1093/carcin/20.6.1127

    Article  CAS  PubMed  Google Scholar 

  47. Garcia-Pelaez J, Barbosa-Matos R, Gullo I et al (2021) Histological and mutational profile of diffuse gastric cancer: current knowledge and future challenges. Mol Oncol 1–27:2841. https://doi.org/10.1002/1878-0261.12948

    Article  CAS  Google Scholar 

  48. Sereno M, Aguayo C, Guillén Ponce C et al (2011) Gastric tumours in hereditary cancer syndromes: clinical features, molecular biology and strategies for prevention. Clin Transl Oncol 13:599–610. https://doi.org/10.1007/s12094-011-0705-y

    Article  PubMed  Google Scholar 

  49. Corso G, Roncalli F, Marrelli D et al (2013) History, pathogenesis, and management of familial gastric cancer: original study of John XXIII’s family. Biomed Res Int 2013:385132. https://doi.org/10.1155/2013/385132

    Article  CAS  PubMed  Google Scholar 

  50. Kohlmann W, Gruber SB (2004) Lynch syndrome. GeneReviews® (updated 2021)

    Google Scholar 

  51. Chung DC, Rustgi AK (1995) DNA mismatch repair and cancer. Gastroenterology 109:1685–1699. https://doi.org/10.1016/0016-5085(95)90660-6

    Article  CAS  PubMed  Google Scholar 

  52. Tutlewska K, Lubinski J, Kurzawski G (2013) Germline deletions in the EPCAM gene as a cause of Lynch syndrome - literature review. Hered Cancer Clin Pract 11:9. https://doi.org/10.1186/1897-4287-11-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Iyer RR, Pluciennik A, Burdett V, Modrich PL (2006) DNA mismatch repair: functions and mechanisms. Chem Rev 106:302–323. https://doi.org/10.1021/cr0404794

    Article  CAS  PubMed  Google Scholar 

  54. Bonadona V, Bonaïti B, Olschwang S et al (2011) Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome. JAMA 305:2304–2310. https://doi.org/10.1001/jama.2011.743

    Article  CAS  PubMed  Google Scholar 

  55. Walsh MD, Buchanan DD, Cummings MC et al (2010) Lynch syndrome-associated breast cancers: clinicopathologic characteristics of a case series from the colon cancer family registry. Clin Cancer Res 16:2214–2224. https://doi.org/10.1158/1078-0432.CCR-09-3058

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Burn J, Bishop DT, Mecklin J-P et al (2008) Effect of aspirin or resistant starch on colorectal neoplasia in the Lynch syndrome. N Engl J Med 359:2567–2578. https://doi.org/10.1056/NEJMoa0801297

    Article  CAS  PubMed  Google Scholar 

  57. Le DT, Uram JN, Wang H et al (2015) PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 372:2509–2520. https://doi.org/10.1056/NEJMoa1500596

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Zhao P, Li L, Jiang X, Li Q (2019) Mismatch repair deficiency/microsatellite instability-high as a predictor for anti-PD-1/PD-L1 immunotherapy efficacy. J Hematol Oncol 12:54. https://doi.org/10.1186/s13045-019-0738-1

    Article  PubMed  PubMed Central  Google Scholar 

  59. Harris CC (1996) Structure and function of the p53 tumor suppressor gene: clues for rational cancer therapeutic strategies. J Natl Cancer Inst 88:1442–1455. https://doi.org/10.1093/jnci/88.20.1442

    Article  CAS  PubMed  Google Scholar 

  60. Ozaki T, Nakagawara A (2011) p53: the attractive tumor suppressor in the cancer research field. J Biomed Biotechnol 2011:603925. https://doi.org/10.1155/2011/603925

    Article  CAS  PubMed  Google Scholar 

  61. Boyd MT, Vlatkovic N (2008) p53: a molecular marker for the detection of cancer. Expert Opin Med Diagn 2:1013–1024. https://doi.org/10.1517/17530059.2.9.1013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Schneider K, Zelley K, Nichols KE, Garber J (1999) Li-Fraumeni Syndrome. GeneReviews® (updated 2019)

    Google Scholar 

  63. Frebourg T, Bajalica Lagercrantz S, Oliveira C et al (2020) Guidelines for the Li-Fraumeni and heritable TP53-related cancer syndromes. Eur J Hum Genet 28:1379–1386. https://doi.org/10.1038/s41431-020-0638-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Li FP, Fraumeni JF (1969) Soft-tissue sarcomas, breast cancer, and other neoplasms. A familial syndrome? Ann Intern Med 71:747–752. https://doi.org/10.7326/0003-4819-71-4-747

    Article  CAS  PubMed  Google Scholar 

  65. Chompret A, Brugières L, Ronsin M et al (2000) P53 germline mutations in childhood cancers and cancer risk for carrier individuals. Br J Cancer 82:1932–1937. https://doi.org/10.1054/bjoc.2000.1167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Nichols KE, Malkin D, Garber JE et al (2001) Germ-line p53 mutations predispose to a wide spectrum of early-onset cancers. Cancer Epidemiol Biomark Prev 10:83–87

    CAS  Google Scholar 

  67. Olivier M, Goldgar DE, Sodha N et al (2003) Li-Fraumeni and related syndromes: correlation between tumor type, family structure, and TP53 genotype. Cancer Res 63:6643–6650

    CAS  PubMed  Google Scholar 

  68. Varley JM (2003) Germline TP53 mutations and Li-Fraumeni syndrome. Hum Mutat 21:313–320. https://doi.org/10.1002/humu.10185

    Article  CAS  PubMed  Google Scholar 

  69. Gonzalez KD, Noltner KA, Buzin CH et al (2009) Beyond Li Fraumeni syndrome: clinical characteristics of families with p53 germline mutations. J Clin Oncol 27:1250–1256. https://doi.org/10.1200/JCO.2008.16.6959

    Article  CAS  PubMed  Google Scholar 

  70. Wong P, Verselis SJ, Garber JE et al (2006) Prevalence of early onset colorectal cancer in 397 patients with classic Li-Fraumeni syndrome. Gastroenterology 130:73–79. https://doi.org/10.1053/j.gastro.2005.10.014

    Article  PubMed  Google Scholar 

  71. Birch JM, Alston RD, McNally RJ et al (2001) Relative frequency and morphology of cancers in carriers of germline TP53 mutations. Oncogene 20:4621–4628. https://doi.org/10.1038/sj.onc.1204621

    Article  CAS  PubMed  Google Scholar 

  72. Bougeard G, Renaux-Petel M, Flaman JM et al (2015) Revisiting Li-Fraumeni syndrome from TP53 mutation carriers. J Clin Oncol 33:2345–2352. https://doi.org/10.1200/JCO.2014.59.5728

    Article  CAS  PubMed  Google Scholar 

  73. Mai PL, Best AF, Peters JA et al (2016) Risks of first and subsequent cancers among TP53 mutation carriers in the National Cancer Institute Li-Fraumeni syndrome cohort. Cancer 122:3673–3681. https://doi.org/10.1002/cncr.30248

    Article  CAS  PubMed  Google Scholar 

  74. Roy R, Chun J, Powell SN (2011) BRCA1 and BRCA2: different roles in a common pathway of genome protection. Nat Rev Cancer 12:68–78. https://doi.org/10.1038/nrc3181

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Foulkes WD, Shuen AY (2013) In brief: BRCA1 and BRCA2. J Pathol 230:347–349. https://doi.org/10.1002/path.4205

    Article  CAS  PubMed  Google Scholar 

  76. Wang Y, Cortez D, Yazdi P et al (2000) BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures. Genes Dev 14:927–939

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Hedenfalk IA, Ringnér M, Trent JM, Borg A (2002) Gene expression in inherited breast cancer. Adv Cancer Res 84:1–34

    Article  CAS  PubMed  Google Scholar 

  78. Xia B, Sheng Q, Nakanishi K et al (2006) Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2. Mol Cell 22:719–729. https://doi.org/10.1016/j.molcel.2006.05.022

    Article  CAS  PubMed  Google Scholar 

  79. Buisson R, Dion-Côté A-M, Coulombe Y et al (2010) Cooperation of breast cancer proteins PALB2 and piccolo BRCA2 in stimulating homologous recombination. Nat Struct Mol Biol 17:1247–1254. https://doi.org/10.1038/nsmb.1915

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Petrucelli N, Daly MB, Pal T (1998) BRCA1- and BRCA2-associated hereditary breast and ovarian cancer. GeneReviews® (updated 2022)

    Google Scholar 

  81. Antoniou A, Pharoah PDP, Narod S et al (2003) Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet 72:1117–1130. https://doi.org/10.1086/375033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Chen S, Parmigiani G (2007) Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol 25:1329–1333. https://doi.org/10.1200/JCO.2006.09.1066

    Article  PubMed  Google Scholar 

  83. Mavaddat N, Peock S, Frost D et al (2013) Cancer risks for BRCA1 and BRCA2 mutation carriers: results from prospective analysis of EMBRACE. J Natl Cancer Inst 105:812–822. https://doi.org/10.1093/jnci/djt095

    Article  CAS  PubMed  Google Scholar 

  84. Tai YC, Domchek S, Parmigiani G, Chen S (2007) Breast cancer risk among male BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst 99:1811–1814. https://doi.org/10.1093/jnci/djm203

    Article  CAS  PubMed  Google Scholar 

  85. Leongamornlert D, Mahmud N, Tymrakiewicz M et al (2012) Germline BRCA1 mutations increase prostate cancer risk. Br J Cancer 106:1697–1701. https://doi.org/10.1038/bjc.2012.146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Kote-Jarai Z, Leongamornlert D, Saunders E et al (2011) BRCA2 is a moderate penetrance gene contributing to young-onset prostate cancer: implications for genetic testing in prostate cancer patients. Br J Cancer 105:1230–1234. https://doi.org/10.1038/bjc.2011.383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Tedaldi G, Tebaldi M, Zampiga V et al (2020) Male breast cancer: results of the application of multigene panel testing to an Italian cohort of patients. Diagnostics (Basel, Switzerland) 10. https://doi.org/10.3390/diagnostics10050269

  88. Thompson D, Easton DF, Breast Cancer Linkage Consortium (2002) Cancer incidence in BRCA1 mutation carriers. J Natl Cancer Inst 94:1358–1365. https://doi.org/10.1093/jnci/94.18.1358

    Article  CAS  PubMed  Google Scholar 

  89. Ghiorzo P, Pensotti V, Fornarini G et al (2012) Contribution of germline mutations in the BRCA and PALB2 genes to pancreatic cancer in Italy. Familial Cancer 11:41–47. https://doi.org/10.1007/s10689-011-9483-5

    Article  CAS  PubMed  Google Scholar 

  90. Iqbal J, Ragone A, Lubinski J et al (2012) The incidence of pancreatic cancer in BRCA1 and BRCA2 mutation carriers. Br J Cancer 107:2005–2009. https://doi.org/10.1038/bjc.2012.483

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Ford D, Easton DF, Bishop DT et al (1994) Risks of cancer in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Lancet 343:692–695. https://doi.org/10.1016/s0140-6736(94)91578-4

    Article  CAS  PubMed  Google Scholar 

  92. Moran A, O’Hara C, Khan S et al (2012) Risk of cancer other than breast or ovarian in individuals with BRCA1 and BRCA2 mutations. Familial Cancer 11:235–242. https://doi.org/10.1007/s10689-011-9506-2

    Article  CAS  PubMed  Google Scholar 

  93. Breast Cancer Linkage Consortium (1999) Cancer risks in BRCA2 mutation carriers. J Natl Cancer Inst 91:1310–1316. https://doi.org/10.1093/jnci/91.15.1310

    Article  Google Scholar 

  94. Fong PC, Boss DS, Yap TA et al (2009) Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med 361:123–134. https://doi.org/10.1056/NEJMoa0900212

    Article  CAS  PubMed  Google Scholar 

  95. Sandhu SK, Schelman WR, Wilding G et al (2013) The poly(ADP-ribose) polymerase inhibitor niraparib (MK4827) in BRCA mutation carriers and patients with sporadic cancer: a phase 1 dose-escalation trial. Lancet Oncol 14:882–892. https://doi.org/10.1016/S1470-2045(13)70240-7

    Article  CAS  PubMed  Google Scholar 

  96. Cortesi L, Rugo HS, Jackisch C (2021) An overview of PARP inhibitors for the treatment of breast cancer. Target Oncol 16:255. https://doi.org/10.1007/s11523-021-00796-4

    Article  PubMed  PubMed Central  Google Scholar 

  97. Audeh MW, Carmichael J, Penson RT et al (2010) Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial. Lancet 376:245–251. https://doi.org/10.1016/S0140-6736(10)60893-8

    Article  CAS  PubMed  Google Scholar 

  98. Tutt A, Robson M, Garber JE et al (2010) Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet (London, England) 376:235–244. https://doi.org/10.1016/S0140-6736(10)60892-6

    Article  CAS  PubMed  Google Scholar 

  99. Sandhu SK, Omlin A, Hylands L et al (2013) Poly (ADP-ribose) polymerase (PARP) inhibitors for the treatment of advanced germline BRCA2 mutant prostate cancer. Ann Oncol 24:1416–1418. https://doi.org/10.1093/annonc/mdt074

    Article  CAS  PubMed  Google Scholar 

  100. Golan T, Hammel P, Reni M et al (2019) Maintenance Olaparib for germline BRCA-mutated metastatic pancreatic cancer. N Engl J Med 381:317–327. https://doi.org/10.1056/NEJMoa1903387

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Hodgson DR, Dougherty BA, Lai Z et al (2018) Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes. Br J Cancer 119:1401–1409. https://doi.org/10.1038/s41416-018-0274-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Li A, Geyer FC, Blecua P et al (2019) Homologous recombination DNA repair defects in PALB2-associated breast cancers. NPJ Breast Cancer 5:23. https://doi.org/10.1038/s41523-019-0115-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Konstantinopoulos PA, Spentzos D, Karlan BY et al (2010) Gene expression profile of BRCAness that correlates with responsiveness to chemotherapy and with outcome in patients with epithelial ovarian cancer. J Clin Oncol 28:3555–3561. https://doi.org/10.1200/JCO.2009.27.5719

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Mateo J, Lord CJ, Serra V et al (2019) A decade of clinical development of PARP inhibitors in perspective. Ann Oncol 30:1437. https://doi.org/10.1093/annonc/mdz192

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Wang Y, Zheng K, Huang Y et al (2021) PARP inhibitors in gastric cancer: beacon of hope. J Exp Clin Cancer Res 40:211. https://doi.org/10.1186/s13046-021-02005-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Ilyas M, Tomlinson IP (1997) The interactions of APC, E-cadherin and beta-catenin in tumour development and progression. J Pathol 182:128–137. https://doi.org/10.1002/(SICI)1096-9896(199706)182:2<128::AID-PATH839>3.0.CO;2-Q

    Article  CAS  PubMed  Google Scholar 

  107. Dinarvand P, Davaro EP, Doan JV et al (2019) Familial adenomatous polyposis syndrome: an update and review of extraintestinal manifestations. Arch Pathol Lab Med 143:1382–1398. https://doi.org/10.5858/arpa.2018-0570-RA

    Article  CAS  PubMed  Google Scholar 

  108. Jasperson KW, Patel SG, Ahnen DJ (1998) APC-associated polyposis conditions. GeneReviews® (updated 2022)

    Google Scholar 

  109. Ma H, Brosens LAA, Offerhaus GJA et al (2018) Pathology and genetics of hereditary colorectal cancer. Pathology 50:49–59. https://doi.org/10.1016/j.pathol.2017.09.004

    Article  CAS  PubMed  Google Scholar 

  110. Knudsen AL, Bülow S, Tomlinson I et al (2010) Attenuated familial adenomatous polyposis: results from an international collaborative study. Color Dis 12:e243–e249. https://doi.org/10.1111/j.1463-1318.2010.02218.x

    Article  CAS  Google Scholar 

  111. Nieuwenhuis MH, Vasen HFA (2007) Correlations between mutation site in APC and phenotype of familial adenomatous polyposis (FAP): a review of the literature. Crit Rev Oncol Hematol 61:153–161. https://doi.org/10.1016/j.critrevonc.2006.07.004

    Article  CAS  PubMed  Google Scholar 

  112. Lynch HT, Smyrk T, McGinn T et al (1995) Attenuated familial adenomatous polyposis (AFAP). A phenotypically and genotypically distinctive variant of FAP. Cancer 76:2427–2433. https://doi.org/10.1002/1097-0142(19951215)76:12<2427::aid-cncr2820761205>3.0.co;2-b

    Article  CAS  PubMed  Google Scholar 

  113. Garrean S, Hering J, Saied A et al (2008) Gastric adenocarcinoma arising from fundic gland polyps in a patient with familial adenomatous polyposis syndrome. Am Surg 74:79–83

    Article  PubMed  Google Scholar 

  114. Arnason T, Liang W-Y, Alfaro E et al (2014) Morphology and natural history of familial adenomatous polyposis-associated dysplastic fundic gland polyps. Histopathology 65:353–362. https://doi.org/10.1111/his.12393

    Article  PubMed  Google Scholar 

  115. Leone PJ, Mankaney G, Sarvapelli S et al (2019) Endoscopic and histologic features associated with gastric cancer in familial adenomatous polyposis. Gastrointest Endosc 89:961–968. https://doi.org/10.1016/j.gie.2018.12.018

    Article  PubMed  Google Scholar 

  116. Mankaney G, Leone P, Cruise M et al (2017) Gastric cancer in FAP: a concerning rise in incidence. Familial Cancer 16:371–376. https://doi.org/10.1007/s10689-017-9971-3

    Article  PubMed  Google Scholar 

  117. Slupska MM, Baikalov C, Luther WM et al (1996) Cloning and sequencing a human homolog (hMYH) of the Escherichia coli mutY gene whose function is required for the repair of oxidative DNA damage. J Bacteriol 178:3885–3892. https://doi.org/10.1128/jb.178.13.3885-3892.1996

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Nielsen M, Infante E, Brand R (2012) MUTYH Polyposis. GeneReviews® (updated 2021)

    Google Scholar 

  119. Hurley JJ, Thomas LE, Walton S-J et al (2018) The impact of chromoendoscopy for surveillance of the duodenum in patients with MUTYH-associated polyposis and familial adenomatous polyposis. Gastrointest Endosc 88:665–673. https://doi.org/10.1016/j.gie.2018.04.2347

    Article  PubMed  Google Scholar 

  120. Spigelman AD, Williams CB, Talbot IC et al (1989) Upper gastrointestinal cancer in patients with familial adenomatous polyposis. Lancet (London, England) 2:783–785. https://doi.org/10.1016/s0140-6736(89)90840-4

    Article  CAS  PubMed  Google Scholar 

  121. Mishina Y, Starbuck MW, Gentile MA et al (2004) Bone morphogenetic protein type IA receptor signaling regulates postnatal osteoblast function and bone remodeling. J Biol Chem 279:27560–27566. https://doi.org/10.1074/jbc.M404222200

    Article  CAS  PubMed  Google Scholar 

  122. Massagué J (2012) TGFβ signalling in context. Nat Rev Mol Cell Biol 13:616–630. https://doi.org/10.1038/nrm3434

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Larsen Haidle J, Howe JR (2003) Juvenile polyposis syndrome. GeneReviews® (updated 2022)

    Google Scholar 

  124. Latchford AR, Neale K, Phillips RKS, Clark SK (2012) Juvenile polyposis syndrome: a study of genotype, phenotype, and long-term outcome. Dis Colon Rectum 55:1038–1043. https://doi.org/10.1097/DCR.0b013e31826278b3

    Article  PubMed  Google Scholar 

  125. Aytac E, Sulu B, Heald B et al (2015) Genotype-defined cancer risk in juvenile polyposis syndrome. Br J Surg 102:114–118. https://doi.org/10.1002/bjs.9693

    Article  CAS  PubMed  Google Scholar 

  126. Ishida H, Ishibashi K, Iwama T (2018) Malignant tumors associated with juvenile polyposis syndrome in Japan. Surg Today 48:253–263. https://doi.org/10.1007/s00595-017-1538-2

    Article  CAS  PubMed  Google Scholar 

  127. Blatter R, Tschupp B, Aretz S et al (2020) Disease expression in juvenile polyposis syndrome: a retrospective survey on a cohort of 221 European patients and comparison with a literature-derived cohort of 473 SMAD4/BMPR1A pathogenic variant carriers. Genet Med 22:1524–1532. https://doi.org/10.1038/s41436-020-0826-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. MacFarland SP, Ebrahimzadeh JE, Zelley K et al (2021) Phenotypic differences in juvenile polyposis syndrome with or without a disease-causing SMAD4/BMPR1A variant. Cancer Prev Res (Phila) 14:215–222. https://doi.org/10.1158/1940-6207.CAPR-20-0348

    Article  CAS  PubMed  Google Scholar 

  129. Howe JR, Roth S, Ringold JC et al (1998) Mutations in the SMAD4/DPC4 gene in juvenile polyposis. Science 280:1086–1088. https://doi.org/10.1126/science.280.5366.1086

    Article  CAS  PubMed  Google Scholar 

  130. Ma C, Giardiello FM, Montgomery EA (2014) Upper tract juvenile polyps in juvenile polyposis patients: dysplasia and malignancy are associated with foveolar, intestinal, and pyloric differentiation. Am J Surg Pathol 38:1618–1626. https://doi.org/10.1097/PAS.0000000000000283

    Article  PubMed  PubMed Central  Google Scholar 

  131. Aretz S, Stienen D, Uhlhaas S et al (2007) High proportion of large genomic deletions and a genotype phenotype update in 80 unrelated families with juvenile polyposis syndrome. J Med Genet 44:702–709. https://doi.org/10.1136/jmg.2007.052506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Brosens LAA, van Hattem A, Hylind LM et al (2007) Risk of colorectal cancer in juvenile polyposis. Gut 56:965–967. https://doi.org/10.1136/gut.2006.116913

    Article  PubMed  PubMed Central  Google Scholar 

  133. Höfting I, Pott G, Stolte M (1993) The syndrome of juvenile polyposis. Leber Magen Darm 23(107–8):111–112

    Google Scholar 

  134. Howe JR, Mitros FA, Summers RW (1998) The risk of gastrointestinal carcinoma in familial juvenile polyposis. Ann Surg Oncol 5:751–756. https://doi.org/10.1007/BF02303487

    Article  CAS  PubMed  Google Scholar 

  135. Agnifili A, Verzaro R, Gola P et al (1999) Juvenile polyposis: case report and assessment of the neoplastic risk in 271 patients reported in the literature. Dig Surg 16:161–166. https://doi.org/10.1159/000018711

    Article  CAS  PubMed  Google Scholar 

  136. Goff V Transparency and disclosure: the route to accountability. Issue Brief (Inst Health Care Costs Solut) 2:1–12

    Google Scholar 

  137. Woodford-Richens K, Bevan S, Churchman M et al (2000) Analysis of genetic and phenotypic heterogeneity in juvenile polyposis. Gut 46:656–660. https://doi.org/10.1136/gut.46.5.656

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Achatz MI, Porter CC, Brugières L et al (2017) Cancer screening recommendations and clinical Management of Inherited Gastrointestinal Cancer Syndromes in childhood. Clin Cancer Res 23:e107–e114. https://doi.org/10.1158/1078-0432.CCR-17-0790

    Article  PubMed  Google Scholar 

  139. Cohen S, Hyer W, Mas E et al (2019) Management of Juvenile Polyposis Syndrome in children and adolescents: a position paper from the ESPGHAN polyposis working group. J Pediatr Gastroenterol Nutr 68:453–462. https://doi.org/10.1097/MPG.0000000000002246

    Article  PubMed  Google Scholar 

  140. Xu X, Jin D, Durgan J, Hall A (2013) LKB1 controls human bronchial epithelial morphogenesis through p114RhoGEF-dependent RhoA activation. Mol Cell Biol 33:2671–2682. https://doi.org/10.1128/MCB.00154-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. McGarrity TJ, Amos CI, Baker MJ (2001) Peutz-Jeghers Syndrome. GeneReviews® (updated 2021)

    Google Scholar 

  142. Lim W, Olschwang S, Keller JJ et al (2004) Relative frequency and morphology of cancers in STK11 mutation carriers. Gastroenterology 126:1788–1794. https://doi.org/10.1053/j.gastro.2004.03.014

    Article  CAS  PubMed  Google Scholar 

  143. Giardiello FM, Brensinger JD, Tersmette AC et al (2000) Very high risk of cancer in familial Peutz-Jeghers syndrome. Gastroenterology 119:1447–1453. https://doi.org/10.1053/gast.2000.20228

    Article  CAS  PubMed  Google Scholar 

  144. Pezzolesi MG, Zbuk KM, Waite KA, Eng C (2007) Comparative genomic and functional analyses reveal a novel cis-acting PTEN regulatory element as a highly conserved functional E-box motif deleted in Cowden syndrome. Hum Mol Genet 16:1058–1071. https://doi.org/10.1093/hmg/ddm053

    Article  CAS  PubMed  Google Scholar 

  145. Yehia L, Eng C (2001) PTEN Hamartoma Tumor Syndrome. GeneReviews® (updated 2021)

    Google Scholar 

  146. Mester J, Eng C (2015) Cowden syndrome: recognizing and managing a not-so-rare hereditary cancer syndrome. J Surg Oncol 111:125–130. https://doi.org/10.1002/jso.23735

    Article  PubMed  Google Scholar 

  147. Tan M-H, Mester JL, Ngeow J et al (2012) Lifetime cancer risks in individuals with germline PTEN mutations. Clin Cancer Res 18:400–407. https://doi.org/10.1158/1078-0432.CCR-11-2283

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Heald B, Mester J, Rybicki L et al (2010) Frequent gastrointestinal polyps and colorectal adenocarcinomas in a prospective series of PTEN mutation carriers. Gastroenterology 139:1927–1933. https://doi.org/10.1053/j.gastro.2010.06.061

    Article  CAS  PubMed  Google Scholar 

  149. Ngeow J, Eng C (2015) PTEN hamartoma tumor syndrome: clinical risk assessment and management protocol. Methods 77–78:11–19. https://doi.org/10.1016/j.ymeth.2014.10.011

    Article  CAS  PubMed  Google Scholar 

  150. Zbuk KM, Eng C (2007) Hamartomatous polyposis syndromes. Nat Clin Pract Gastroenterol Hepatol 4:492–502. https://doi.org/10.1038/ncpgasthep0902

    Article  CAS  PubMed  Google Scholar 

  151. Rosty C (2018) The role of the surgical pathologist in the diagnosis of gastrointestinal polyposis syndromes. Adv Anat Pathol 25:1–13. https://doi.org/10.1097/PAP.0000000000000173

    Article  PubMed  Google Scholar 

  152. Adams DR, Eng CM (2018) Next-generation sequencing to diagnose suspected genetic disorders. N Engl J Med 379:1353–1362. https://doi.org/10.1056/NEJMra1711801

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy

    Gianluca Tedaldi

  2. i3S, Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal

    Celina São José & Carla Oliveira

  3. IPATIMUP, Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal

    Celina São José & Carla Oliveira

  4. Doctoral Programme in Biomedicine, Faculty of Medicine, University of Porto, Porto, Portugal

    Celina São José

  5. FMUP - Faculty of Medicine of the University of Porto, Porto, Portugal

    Carla Oliveira

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  1. Gianluca Tedaldi
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  2. Celina São José
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  3. Carla Oliveira
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Correspondence to Gianluca Tedaldi .

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  1. European Institute of Oncology, University of Milan, Milan, Italy

    Giovanni Corso

  2. European Institute of Oncology, University of Milan, Milan, Italy

    Paolo Veronesi

  3. University of Siena, Siena, Italy

    Franco Roviello

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Tedaldi, G., São José, C., Oliveira, C. (2023). Other Syndromes and Genes Associated with Gastric Cancer Predisposition. In: Corso, G., Veronesi, P., Roviello, F. (eds) Hereditary Gastric and Breast Cancer Syndrome. Springer, Cham. https://doi.org/10.1007/978-3-031-21317-5_7

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