CYP3A7*1C allele: linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers.
Alleles
Breast Neoplasms
/ enzymology
Case-Control Studies
Cytochrome P-450 CYP3A
/ genetics
Estrone
/ analogs & derivatives
Female
Genome-Wide Association Study
Humans
Polymorphism, Single Nucleotide
Pregnanediol
/ analogs & derivatives
Premenopause
Progesterone
/ urine
Receptors, Estrogen
/ metabolism
Receptors, Progesterone
/ metabolism
Journal
British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
27
04
2020
accepted:
05
11
2020
revised:
21
10
2020
pubmed:
27
1
2021
medline:
15
7
2021
entrez:
26
1
2021
Statut:
ppublish
Résumé
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. 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. 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 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.
Sections du résumé
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
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.
Identifiants
pubmed: 33495599
doi: 10.1038/s41416-020-01185-w
pii: 10.1038/s41416-020-01185-w
pmc: PMC7884683
doi:
Substances chimiques
Receptors, Estrogen
0
Receptors, Progesterone
0
pregnanediol-3 alpha-glucuronide
1852-49-9
estrone-3-glucuronide
2479-90-5
Estrone
2DI9HA706A
Progesterone
4G7DS2Q64Y
CYP3A7 protein, human
EC 1.14.14.1
Cytochrome P-450 CYP3A
EC 1.14.14.1
Pregnanediol
JR3JD1Y22C
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
842-854Subventions
Organisme : NCI NIH HHS
ID : U19 CA148065
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES010126
Pays : United States
Organisme : Medical Research Council
ID : MR/N003284/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0401527
Pays : United Kingdom
Organisme : Medical Research Council
ID : G1000143
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 10118
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 14136
Pays : United Kingdom
Investigateurs
Anne-Lise Børresen-Dale
(AL)
Grethe I Grenaker Alnæs
(GIG)
Kristine K Sahlberg
(KK)
Lars Ottestad
(L)
Rolf Kåresen
(R)
Ellen Schlichting
(E)
Marit Muri Holmen
(MM)
Toril Sauer
(T)
Vilde Haakensen
(V)
Olav Engebråten
(O)
Bjørn Naume
(B)
Alexander Fosså
(A)
Cecile E Kiserud
(CE)
Kristin V Reinertsen
(KV)
Åslaug Helland
(Å)
Margit Riis
(M)
Jürgen Geisler
(J)
David D L Bowtell
(DDL)
Anna deFazio
(A)
Penelope M Webb
(PM)
Georgia Chenevix-Trench
(G)
Christine Clarke
(C)
Deborah Marsh
(D)
Rodney Scott
(R)
Robert Baxter
(R)
Desmond Yip
(D)
Jane Carpenter
(J)
Alison Davis
(A)
Nirmala Pathmanathan
(N)
Peter Simpson
(P)
Dinny Graham
(D)
Mythily Sachchithananthan
(M)
David Amor
(D)
Lesley Andrews
(L)
Yoland Antill
(Y)
Rosemary Balleine
(R)
Jonathan Beesley
(J)
Ian Bennett
(I)
Michael Bogwitz
(M)
Leon Botes
(L)
Meagan Brennan
(M)
Melissa Brown
(M)
Michael Buckley
(M)
Jo Burke
(J)
Phyllis Butow
(P)
Liz Caldon
(L)
Ian Campbell
(I)
Deepa Chauhan
(D)
Manisha Chauhan
(M)
Georgia Chenevix-Trench
(G)
Alice Christian
(A)
Paul Cohen
(P)
Alison Colley
(A)
Ashley Crook
(A)
James Cui
(J)
Margaret Cummings
(M)
Sarah-Jane Dawson
(SJ)
Anna DeFazio
(A)
Martin Delatycki
(M)
Rebecca Dickson
(R)
Joanne Dixon
(J)
Ted Edkins
(T)
Stacey Edwards
(S)
Gelareh Farshid
(G)
Andrew Fellows
(A)
Georgina Fenton
(G)
Michael Field
(M)
James Flanagan
(J)
Peter Fong
(P)
Laura Forrest
(L)
Stephen Fox
(S)
Juliet French
(J)
Michael Friedlander
(M)
Clara Gaff
(C)
Mike Gattas
(M)
Peter George
(P)
Sian Greening
(S)
Marion Harris
(M)
Stewart Hart
(S)
Nick Hayward
(N)
John Hopper
(J)
Cass Hoskins
(C)
Clare Hunt
(C)
Paul James
(P)
Mark Jenkins
(M)
Alexa Kidd
(A)
Judy Kirk
(J)
Jessica Koehler
(J)
James Kollias
(J)
Sunil Lakhani
(S)
Mitchell Lawrence
(M)
Geoff Lindeman
(G)
Lara Lipton
(L)
Liz Lobb
(L)
Graham Mann
(G)
Deborah Marsh
(D)
Sue Anne McLachlan
(SA)
Bettina Meiser
(B)
Roger Milne
(R)
Sophie Nightingale
(S)
Shona O'Connell
(S)
Sarah O'Sullivan
(S)
David Gallego Ortega
(DG)
Nick Pachter
(N)
Briony Patterson
(B)
Amy Pearn
(A)
Kelly Phillips
(K)
Ellen Pieper
(E)
Edwina Rickard
(E)
Bridget Robinson
(B)
Mona Saleh
(M)
Elizabeth Salisbury
(E)
Christobel Saunders
(C)
Jodi Saunus
(J)
Rodney Scott
(R)
Clare Scott
(C)
Adrienne Sexton
(A)
Andrew Shelling
(A)
Peter Simpson
(P)
Melissa Southey
(M)
Amanda Spurdle
(A)
Jessica Taylor
(J)
Renea Taylor
(R)
Heather Thorne
(H)
Alison Trainer
(A)
Kathy Tucker
(K)
Jane Visvader
(J)
Logan Walker
(L)
Rachael Williams
(R)
Ingrid Winship
(I)
Mary Ann Young
(MA)
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