CYP3A7*1C allele: linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers

Johnson, N; Maguire, S; Morra, A; Kapoor, PM; Tomczyk, K; Jones, ME; Schoemaker, MJ; Gilham, C; Bolla, MK; Wang, Q; Dennis, J; Nbcs Collaborators,; Aocs Group,; Abctb Investigators,; kConFab Investigators,; includes Lindeman, GJ

Author(s): Johnson, N; Maguire, S; Morra, A; Kapoor, PM; Tomczyk, K; Jones, ME; Schoemaker, MJ; Gilham, C; Bolla, MK; Wang, Q; Dennis, J; Nbcs Collaborators,; Aocs Group,; Abctb Investigators,; kConFab Investigators,; includes Lindeman, GJ;
Details: Publication Year 2021-02,Volume 124,Issue #4,Page 842-854
Journal Title: British Journal of Cancer
Abstract: BACKGROUND: Epidemiological studies provide strong evidence for a role of endogenous sex hormones in the aetiology of breast cancer. The aim of this analysis was to identify genetic variants that are associated with urinary sex-hormone levels and breast cancer risk. METHODS: We carried out a genome-wide association study of urinary oestrone-3-glucuronide and pregnanediol-3-glucuronide levels in 560 premenopausal women, with additional analysis of progesterone levels in 298 premenopausal women. To test for the association with breast cancer risk, we carried out follow-up genotyping in 90,916 cases and 89,893 controls from the Breast Cancer Association Consortium. All women were of European ancestry. RESULTS: For pregnanediol-3-glucuronide, there were no genome-wide significant associations; for oestrone-3-glucuronide, we identified a single peak mapping to the CYP3A locus, annotated by rs45446698. The minor rs45446698-C allele was associated with lower oestrone-3-glucuronide (-49.2%, 95% CI -56.1% to -41.1%, P = 3.1 x 10(-18)); in follow-up analyses, rs45446698-C was also associated with lower progesterone (-26.7%, 95% CI -39.4% to -11.6%, P = 0.001) and reduced risk of oestrogen and progesterone receptor-positive breast cancer (OR = 0.86, 95% CI 0.82-0.91, P = 6.9 x 10(-8)). CONCLUSIONS: The CYP3A7*1C allele is associated with reduced risk of hormone receptor-positive breast cancer possibly mediated via an effect on the metabolism of endogenous sex hormones in premenopausal women.
Publisher: NPG
Research Division(s): Cancer Biology And Stem Cells
PubMed ID: 33495599
Publisher's Version: https://doi.org/10.1038/s41416-020-01185-w
Open Access at Publisher's Site: https://doi.org/10.1038/s41416-020-01185-w
Terms of Use/Rights Notice: Refer to copyright notice on published article.
Documents: Johnson N etal_Br J Cancer_2021.pdf - (0.94MB, application/pdf)

Creation Date: 2021-05-11 02:09:49

Last Modified: 2021-05-11 02:32:20