Common variability in oestrogen-related genes and pancreatic ductal adenocarcinoma risk in women

. 2022 Oct 27 ; 12 (1) : 18100. [epub] 20221027

Jazyk angličtina Země Anglie, Velká Británie Médium electronic

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/pmid36302831

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

Odkazy

PubMed 36302831
PubMed Central PMC9613634
DOI 10.1038/s41598-022-22973-9
PII: 10.1038/s41598-022-22973-9
Knihovny.cz E-zdroje

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.

1st Faculty of Medicine Institute of Biology and Medical Genetics Charles University Prague Czech Republic

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 General Visceral and Thoracic Surgery University Medical Center Hamburg Eppendorf Hamburg Germany

Department of Medical Oncology Amsterdam UMC Location University of Amsterdam Meibergdreef 9 Amsterdam The Netherlands

Department of Molecular Biology of Cancer Institute of Experimental Medicine of the Czech Academy of Sciences Prague Czech Republic

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 Clinical Epidemiology and Aging Research German Cancer Research Center Heidelberg Germany

Division of Gastroenterology and Research Laboratory Fondazione IRCCS Casa Sollievo Della Sofferenza Hospital San Giovanni Rotondo Italy

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

Gastroenterology and Gastrointestinal Endoscopy Unit Vita Salute San Raffaele University IRCCS San Raffaele Scientific Institute Milan Italy

Gastroenterology Department and Institute for Digestive Research Lithuanian University of Health Sciences Kaunas Lithuania

General Surgery Department of Translational Research and New Technologies in Medicine and Surgery University of Pisa Pisa Italy

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 for Applied Science and Technology in Health Carlos Chagas Institute Oswaldo Cruz Foundation Curitiba Brazil

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

Pancreato Biliary Endoscopy and Endoscopic Ultrasound Pancreas Translational and Clinical Research Center San Raffaele Scientific Institute IRCCS Milan Italy

Potenza Medical County Association Potenza Italy

Surgery Clinic 3rd Faculty of Medicine Charles University Prague Czech Republic

University of Utrecht Utrecht The Netherlands

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