Common variability in oestrogen-related genes and pancreatic ductal adenocarcinoma risk in women
Jazyk angličtina Země Anglie, Velká Británie Médium electronic
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
MC_UU_12015/1
Medical Research Council - United Kingdom
C864/A14136
Cancer Research UK - United Kingdom
MR/N003284/1
Medical Research Council - United Kingdom
G0401527
Medical Research Council - United Kingdom
14136
Cancer Research UK - United Kingdom
G1000143
Medical Research Council - United Kingdom
PubMed
36302831
PubMed Central
PMC9613634
DOI
10.1038/s41598-022-22973-9
PII: 10.1038/s41598-022-22973-9
Knihovny.cz E-zdroje
- MeSH
- adenokarcinom * patologie MeSH
- duktální karcinom pankreatu * patologie MeSH
- estrogeny genetika MeSH
- lidé MeSH
- nádory slinivky břišní * epidemiologie genetika patologie MeSH
- pregnenolon MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- estrogeny MeSH
- pregnenolon MeSH
The incidence of pancreatic ductal adenocarcinoma (PDAC) is different among males and females. This disparity cannot be fully explained by the difference in terms of exposure to known risk factors; therefore, the lower incidence in women could be attributed to sex-specific hormones. A two-phase association study was conducted in 12,387 female subjects (5436 PDAC cases and 6951 controls) to assess the effect on risk of developing PDAC of single nucleotide polymorphisms (SNPs) in 208 genes involved in oestrogen and pregnenolone biosynthesis and oestrogen-mediated signalling. In the discovery phase 14 polymorphisms showed a statistically significant association (P < 0.05). In the replication none of the findings were validated. In addition, a gene-based analysis was performed on the 208 selected genes. Four genes (NR5A2, MED1, NCOA2 and RUNX1) were associated with PDAC risk, but only NR5A2 showed an association (P = 4.08 × 10-5) below the Bonferroni-corrected threshold of statistical significance. In conclusion, despite differences in incidence between males and females, our study did not identify an effect of common polymorphisms in the oestrogen and pregnenolone pathways in relation to PDAC susceptibility. However, we validated the previously reported association between NR5A2 gene variants and PDAC risk.
ARC NET Centre for Applied Research on Cancer University and Hospital Trust of Verona Verona Italy
Biomedical Center Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic
Blood Transfusion Service Azienda Ospedaliero Universitaria Meyer Florence Italy
Cancer Center Amsterdam Imaging and Biomarkers Amsterdam The Netherlands
Center for Translational Medicine Semmelweis University Budapest Hungary
Centre for Translational Medicine Department of Medicine University of Szeged Szeged Hungary
Centre for Translational Medicine Semmelweis University Budapest Hungary
Department DIMED Laboratory Medicine University of Padova Padua Italy
Department DISCOG University of Padova Padua Italy
Department of Biology University of Pisa 56126 Pisa Italy
Department of Biomedical Sciences Humanitas University Milan Italy
Department of Digestive Tract Diseases Medical University of Lodz Lodz Poland
Department of General Surgery University of Heidelberg Heidelberg Germany
Department of Oncology Faculty of Medicine and Dentistry Palacký University Olomouc Czech Republic
Department of Surgery Erasmus MC University Medical Center Rotterdam The Netherlands
Digestive and Liver Disease Unit Sant'Andrea Hospital Rome Italy
Division of Cancer Epidemiology German Cancer Research Center Heidelberg Germany
Division of General and Transplant Surgery Pisa University Hospital Pisa Italy
Division of Pancreatic Diseases Heart and Vascular Center Semmelweis University Budapest Hungary
Division of Preventive Oncology German Cancer Research Center Heidelberg Germany
Genomic Epidemiology Group German Cancer Research Center Heidelberg Germany
German Cancer Consortium Heidelberg Germany
Institute for Translational Medicine Medical School University of Pécs Pécs Hungary
János Szentágothai Research Center University of Pécs Pécs Hungary
Laboratory of Biology Medical School National and Kapodistrian University of Athens Athens Greece
Medical Faculty Heidelberg Heidelberg University Heidelberg Germany
Network Aging Research Heidelberg University Heidelberg Germany
Oncology of Massa Carrara Oncological Department Azienda USL Toscana Nord Ovest Carrara Italy
Pancreatic Surgery Unit IRCCS Humanitas Research Hospital Milan Italy
Potenza Medical County Association Potenza Italy
Surgery Clinic 3rd Faculty of Medicine Charles University Prague Czech Republic
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