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.