Journal Article

DKFZ-2022-02551

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Common variability in oestrogen-related genes and pancreatic ductal adenocarcinoma risk in women

Peduzzi, G. ; Archibugi, L. ; Katzke, V.DKFZ* ; Gentiluomo, M. ; Capurso, G. ; Milanetto, A. C. ; Gazouli, M. ; Goetz, M. ; Brenner, H.DKFZ* ; Vermeulen, R. C. H. ; Talar-Wojnarowska, R. ; Vanella, G. ; Tavano, F. ; Lucchesi, M. ; Mohelnikova-Duchonova, B. ; Chen, X.DKFZ* ; Kiudelis, V. ; Hegyi, P. ; Oliverius, M. ; Stocker, H.DKFZ* ; Stornello, C. ; Vodickova, L. ; Souček, P. ; Neoptolemos, J. P. ; Testoni, S. G. G. ; Morelli, L. ; Lawlor, R. T. ; Basso, D. ; Izbicki, J. R. ; Ermini, S. ; Kupcinskas, J. ; Pezzilli, R. ; Boggi, U. ; van Laarhoven, H. W. M. ; Szentesi, A. ; Erőss, B. ; Capretti, G. ; Schöttker, B.DKFZ* ; Skieceviciene, J. ; Aoki, M. N. ; van Eijck, C. H. J. ; Cavestro, G. M. ; Canzian, F. (Last author)DKFZ* ; Campa, D.

2022
Macmillan Publishers Limited, part of Springer Nature [London]

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Please use a persistent id in citations: doi:10.1038/s41598-022-22973-9

Abstract: 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.

Note: #LA:C055#

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Contributing Institute(s):

1. C020 Epidemiologie von Krebs (C020)
2. C070 Klinische Epidemiologie und Alternf. (C070)
3. Präventive Onkologie (C120)
4. C055 Genomische Epidemiologie (C055)
5. DKTK HD zentral (HD01)

Research Program(s):

1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2022

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