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

Johnson, Nichola ; Augustinsson, Annelie LU ; Brenner, Hermann LU ; Burwinkel, Barbara ; Hall, Per LU ; Olsson, Håkan LU orcid and Fletcher, Olivia (2021) In British Journal of Cancer 124(4). p.842-854
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... (More)

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 × 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 × 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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
British Journal of Cancer
volume
124
issue
4
pages
842 - 854
publisher
Nature Publishing Group
external identifiers
  • scopus:85099996359
  • pmid:33495599
ISSN
1532-1827
DOI
10.1038/s41416-020-01185-w
language
English
LU publication?
yes
id
086a2177-8658-4798-915e-987a9366175b
date added to LUP
2021-02-01 00:51:06
date last changed
2025-10-14 12:23:17
@article{086a2177-8658-4798-915e-987a9366175b,
  abstract     = {{<p>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.</p><p>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.</p><p>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 × 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 × 10-8).</p><p>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.</p>}},
  author       = {{Johnson, Nichola and Augustinsson, Annelie and Brenner, Hermann and Burwinkel, Barbara and Hall, Per and Olsson, Håkan and Fletcher, Olivia}},
  issn         = {{1532-1827}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{4}},
  pages        = {{842--854}},
  publisher    = {{Nature Publishing Group}},
  series       = {{British Journal of Cancer}},
  title        = {{CYP3A7*1C allele : linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers}},
  url          = {{http://dx.doi.org/10.1038/s41416-020-01185-w}},
  doi          = {{10.1038/s41416-020-01185-w}},
  volume       = {{124}},
  year         = {{2021}},
}