Open Access Peer-reviewed

Genetic Aspects of Celiac Disease in Association with Pancreatic Tumors

Pavel Procházka
Department of the Molecular Biology of Cancer, Institute of Experimental Medicine AS CR, Prague, Czech Republic
International Journal of Celiac Disease. 2014, 2(3), 93-96. DOI: 10.12691/ijcd-2-3-6
Published online: August 25, 2017

Abstract

Celiac disease stands out as a major health problem with a frequent association with many other disorders. Studies show an increased risk of developing pancreatitis and after that pancreatic cancer in patients with celiac disease. A frequent occurrence and a remarkably close association with the HLA-DQ2 and/or DQ8 gene loci represent main genetic characteristic of celiac disease. A particular association was found with chromosome 15q26 and 6q21-22. On the other hand pancreatic tumors are known for associations with CTNNB1, VHL, CDKN2A, KRAS, TP53, RNF43, SMAD4, GNAS, PRSS1, ATM, BRCA1, BRCA2, PALB2, STK11 and hereditary non-polyposis colorectal cancer syndrome genes. Recent genetic mapping suggests that a large field of opportunities exists for better understanding of both diseases.

Keywords:

celiac disease, pancreatic tumors, HLA-DQ2 gene locus, DQ8 gene locus, KRAS, BRCA1/2
[1]  Ciacci, C., et al., Allergy prevalence in adult celiac disease. J Allergy ClinImmunol, 2004. 113(6): p. 1199-203.View Article  PubMed
 
[2]  Ludvigsson, J.F., S.M. Montgomery, and A. Ekbom, Risk of pancreatitis in 14,000 individuals with celiac disease. ClinGastroenterolHepatol, 2007. 5(11): p. 1347-53.View Article  PubMed
 
[3]  Sadr-Azodi, O., et al.. Patients with celiac disease have an increased risk for pancreatitis. ClinGastroenterolHepatol, 2012. 10(10): p. 1136-1142 e3.
 
[4]  DiMagno, M.J. and E.P. DiMagno, Chronic pancreatitis. CurrOpinGastroenterol, 2013. 29(5): p. 531-6.View Article  PubMed
 
[5]  Sziksz, E., et al., Coeliac Disease: From Triggering Factors to Treatment. International Journal of Celiac Disease, 2013. 1(1): p. 9-13.
 
[6]  Schuppan, D., Current concepts of celiac disease pathogenesis. Gastroenterology, 2000. 119(1): p. 234-42.View Article  PubMed
 
[7]  Romanos, J., et al., Analysis of HLA and non-HLA alleles can identify individuals at high risk for celiac disease. Gastroenterology, 2009. 137(3): p. 834-40, 840 e1-3.
 
[8]  Trynka, G., et al., Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaBsignalling. Gut, 2009. 58(8): p. 1078-83.View Article  PubMed
 
[9]  Susi, M., et al., Candidate gene region 15q26 and genetic susceptibility to coeliac disease in Finnish families.Scand J Gastroenterol, 2001. 36(4): p. 372-4.View Article  PubMed
 
[10]  Latiano, A., et al., Analysis of candidate genes on chromosomes 5q and 19p in celiac disease. J PediatrGastroenterolNutr, 2007. 45(2): p. 180-6.View Article  PubMed
 
[11]  Einarsdottir, E., et al., Multiple independent variants in 6q21-22 associated with susceptibility to celiac disease in the Dutch, Finnish and Hungarian populations. Eur J Hum Genet, 2011. 19(6): p. 682-6.View Article  PubMed
 
[12]  Kaukinen, K., et al., HLA-DQ typing in the diagnosis of celiac disease. Am J Gastroenterol, 2002.97(3): p. 695-9.View Article  PubMed
 
[13]  Al-Toma, A., et al., Human leukocyte antigen-DQ2 homozygosity and the development of refractory celiac disease and enteropathy-associated T-cell lymphoma. ClinGastroenterolHepatol, 2006. 4(3): p. 315-9.View Article  PubMed
 
[14]  Pietzak, M.M., et al., Stratifying risk for celiac disease in a large at-risk United States population by using HLA alleles. ClinGastroenterolHepatol, 2009. 7(9): p. 966-71.View Article  PubMed
 
[15]  Hunt, K.A., et al., Newly identified genetic risk variants for celiac disease related to the immune response. Nat Genet, 2008. 40(4): p. 395-402.View Article  PubMed
 
[16]  Lennon, A.M., et al., The Early Detection of Pancreatic Cancer: What Will It Take to Diagnose and Treat Curable Pancreatic Neoplasia? Cancer Res, 2014. 74(13): p. 3381-3389.View Article  PubMed
 
[17]  Porta, M., et al., Cigarette smoking and K-ras mutations in pancreas, lung and colorectal adenocarcinomas: etiopathogenic similarities, differences and paradoxes. Mutat Res, 2009. 682(2-3): p. 83-93.View Article  PubMed
 
[18]  Hruban, R.H., A. Maitra, and M. Goggins, Update on pancreatic intraepithelial neoplasia. Int J ClinExpPathol, 2008. 1(4): p. 306-16.
 
[19]  Quinlan, M.P., et al., Activated Kras, but not Hras or Nras, may initiate tumors of endodermal origin via stem cell expansion. Mol Cell Biol, 2008. 28(8): p. 2659-74.View Article  PubMed
 
[20]  Allegra, C.J., et al., American Society of Clinical Oncology provisional clinical opinion: testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy. J ClinOncol, 2009. 27(12): p. 2091-6.View Article  PubMed
 
[21]  Halilovic, E., et al., PIK3CA mutation uncouples tumor growth and cyclin D1 regulation from MEK/ERK and mutant KRAS signaling. Cancer Res, 2010. 70(17): p. 6804-14.View Article  PubMed
 
[22]  Murphy, K.M., et al., Evaluation of candidate genes MAP2K4, MADH4, ACVR1B, and BRCA2 in familial pancreatic cancer: deleterious BRCA2 mutations in 17%. Cancer Res, 2002. 62(13): p. 3789-93. PubMed
 
[23]  Hahn, S.A., et al., BRCA2 germline mutations in familial pancreatic carcinoma. J Natl Cancer Inst, 2003. 95(3): p. 214-21.View Article  PubMed
 
[24]  Iqbal, J., et al., The incidence of pancreatic cancer in BRCA1 and BRCA2 mutation carriers. Br J Cancer, 2012. 107(12): p. 2005-9.View Article  PubMed
 
[25]  Ferrone, C.R., et al., BRCA germline mutations in Jewish patients with pancreatic adenocarcinoma. J ClinOncol, 2009. 27(3): p. 433-8.View Article  PubMed
 
[26]  Lal, G., et al., Inherited predisposition to pancreatic adenocarcinoma: role of family history and germ-line p16, BRCA1, and BRCA2 mutations. Cancer Res, 2000. 60(2): p. 409-16. PubMed
 
[27]  Jones, S., et al., Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. Science, 2009. 324(5924): p. 217.View Article  PubMed
 
[28]  Tischkowitz, M.D., et al., Analysis of the gene coding for the BRCA2-interacting protein PALB2 in familial and sporadic pancreatic cancer. Gastroenterology, 2009. 137(3): p. 1183-6.View Article  PubMed
 
[29]  Slater, E.P., et al., PALB2 mutations in European familial pancreatic cancer families.Clin Genet, 2010. 78(5): p. 490-4.View Article  PubMed
 
[30]  Giardiello, F.M., et al., Very high risk of cancer in familial Peutz-Jeghers syndrome. Gastroenterology, 2000. 119(6): p. 1447-53.View Article  PubMed
 
[31]  Rebours, V., et al., Risk of pancreatic adenocarcinoma in patients with hereditary pancreatitis: a national exhaustive series. Am J Gastroenterol, 2008.103(1): p. 111-9.View Article  PubMed
 
[32]  Howes, N., et al., Clinical and genetic characteristics of hereditary pancreatitis in Europe. ClinGastroenterolHepatol, 2004. 2(3): p. 252-61.View Article
 
[33]  Vymetalkova, V.P., et al., Molecular characteristics of mismatch repair genes in sporadic colorectal tumors in Czech patients. BMC Med Genet, 2014. 15: p. 17.View Article  PubMed
 
[34]  Vasen, H.F., et al., Risk of developing pancreatic cancer in families with familial atypical multiple mole melanoma associated with a specific 19 deletion of p16 (p16-Leiden).Int J Cancer, 2000. 87(6): p. 809-11.View Article
 
[35]  Lundin, K.E. and L.M. Sollid, Advances in coeliac disease. CurrOpinGastroenterol, 2014. 30(2): p. 154-62.View Article  PubMed