Journal Article DKFZ-2018-00024

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Do pancreatic cancer and chronic pancreatitis share the same genetic risk factors? A PANcreatic Disease ReseArch (PANDoRA) consortium investigation.

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2018
Wiley-Liss Bognor Regis

International journal of cancer 142(2), 290 - 296 () [10.1002/ijc.31047]
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Abstract: Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive tumor with a five-year survival of less than 6%. Chronic pancreatitis (CP), an inflammatory process in of the pancreas, is a strong risk factor for PDAC. Several genetic polymorphisms have been discovered as susceptibility loci for both CP and PDAC. Since CP and PDAC share a consistent number of epidemiologic risk factors, the aim of this study was to investigate whether specific CP risk loci also contribute to PDAC susceptibility. We selected five common SNPs (rs11988997, rs379742, rs10273639, rs2995271 and rs12688220) that were identified as susceptibility markers for CP and analyzed them in 2,914 PDAC cases, 356 CP cases and 5,596 controls retrospectively collected in the context of the international PANDoRA consortium. We found a weak association between the minor allele of the PRSS1-PRSS2-rs10273639 and an increased risk of developing PDAC (ORhomozygous  = 1.19, 95% CI 1.02-1.38, p = 0.023). Additionally all the SNPs confirmed statistically significant associations with risk of developing CP, the strongest being PRSS1-PRSS2-rs10273639 (ORheterozygous  = 0.51, 95% CI 0.39-0.67, p = 1.10 × 10-6 ) and MORC4-rs 12837024 (ORhomozygous  = 2.07 (1.55-2.77, ptrend  = 0.7 × 10-11 ). Taken together, the results from our study do not support variants rs11988997, rs379742, rs10273639, rs2995271 and rs12688220 as strong predictors of PDAC risk, but further support the role of these SNPs in CP susceptibility. Our study suggests that CP and PDAC probably do not share genetic susceptibility, at least in terms of high frequency variants.

Keyword(s): Biomarkers, Tumor ; MORC4 protein, human ; Nuclear Proteins ; PRSS2 protein, human ; Trypsinogen ; PRSS1 protein, human ; Trypsin

Classification:

Contributing Institute(s):
  1. C055 Genomische Epidemiologie (C055)
  2. C020 Epidemiologie von Krebs (C020)
  3. C070 Klinische Epidemiologie und Alternf. (C070)
  4. Präventive Onkologie (G110)
  5. DKTK Heidelberg (L101)
Research Program(s):
  1. 313 - Cancer risk factors and prevention (POF3-313) (POF3-313)

Appears in the scientific report 2018
Database coverage:
Medline ; BIOSIS Previews ; Current Contents - Life Sciences ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; NationallizenzNationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection
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 Record created 2018-01-18, last modified 2024-02-29



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