Dataset Information

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

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?×?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.

SUBMITTER: Johnson N

PROVIDER: S-EPMC7884683 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

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

Johnson Nichola N Maguire Sarah S Morra Anna A Kapoor Pooja Middha PM Tomczyk Katarzyna K Jones Michael E ME Schoemaker Minouk J MJ Gilham Clare C Bolla Manjeet K MK Wang Qin Q Dennis Joe J Ahearn Thomas U TU Andrulis Irene L IL Anton-Culver Hoda H Antonenkova Natalia N NN Arndt Volker V Aronson Kristan J KJ Augustinsson Annelie A Baynes Caroline C Freeman Laura E Beane LEB Beckmann Matthias W MW Benitez Javier J Bermisheva Marina M Blomqvist Carl C Boeckx Bram B Bogdanova Natalia V NV Bojesen Stig E SE Brauch Hiltrud H Brenner Hermann H Burwinkel Barbara B Campa Daniele D Canzian Federico F Castelao Jose E JE Chanock Stephen J SJ Chenevix-Trench Georgia G Clarke Christine L CL Conroy Don M DM Couch Fergus J FJ Cox Angela A Cross Simon S SS Czene Kamila K Dörk Thilo T Eliassen A Heather AH Engel Christoph C Evans D Gareth DG Fasching Peter A PA Figueroa Jonine J Floris Giuseppe G Flyger Henrik H Gago-Dominguez Manuela M Gapstur Susan M SM García-Closas Montserrat M Gaudet Mia M MM Giles Graham G GG Goldberg Mark S MS González-Neira Anna A Guénel Pascal P Hahnen Eric E Haiman Christopher A CA Håkansson Niclas N Hall Per P Hamann Ute U Harrington Patricia A PA Hart Steven N SN Hooning Maartje J MJ Hopper John L JL Howell Anthony A Hunter David J DJ Jager Agnes A Jakubowska Anna A John Esther M EM Kaaks Rudolf R Keeman Renske R Khusnutdinova Elza E Kitahara Cari M CM Kosma Veli-Matti VM Koutros Stella S Kraft Peter P Kristensen Vessela N VN Kurian Allison W AW Lambrechts Diether D Le Marchand Loic L Linet Martha M Lubiński Jan J Mannermaa Arto A Manoukian Siranoush S Margolin Sara S Martens John W M JWM Mavroudis Dimitrios D Mayes Rebecca R Meindl Alfons A Milne Roger L RL Neuhausen Susan L SL Nevanlinna Heli H Newman William G WG Nielsen Sune F SF Nordestgaard Børge G BG Obi Nadia N Olshan Andrew F AF Olson Janet E JE Olsson Håkan H Orban Ester E Park-Simon Tjoung-Won TW Peterlongo Paolo P Plaseska-Karanfilska Dijana D Pylkäs Katri K Rennert Gad G Rennert Hedy S HS Ruddy Kathryn J KJ Saloustros Emmanouil E Sandler Dale P DP Sawyer Elinor J EJ Schmutzler Rita K RK Scott Christopher C Shu Xiao-Ou XO Simard Jacques J Smichkoska Snezhana S Sohn Christof C Southey Melissa C MC Spinelli John J JJ Stone Jennifer J Tamimi Rulla M RM Taylor Jack A JA Tollenaar Rob A E M RAEM Tomlinson Ian I Troester Melissa A MA Truong Thérèse T Vachon Celine M CM van Veen Elke M EM Wang Sophia S SS Weinberg Clarice R CR Wendt Camilla C Wildiers Hans H Winqvist Robert R Wolk Alicja A Zheng Wei W Ziogas Argyrios A Dunning Alison M AM Pharoah Paul D P PDP Easton Douglas F DF Howie A Forbes AF Peto Julian J Dos-Santos-Silva Isabel I Swerdlow Anthony J AJ Chang-Claude Jenny J Schmidt Marjanka K MK Orr Nick N Fletcher Olivia O

British journal of cancer 20210126 4

<h4>Background</h4>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.<h4>Methods</h4>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 premenopa ...[more]

PMID: 33495599

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Project description:There is growing interest in the endocrine treatment (ET) of premenopausal women with hormone receptor positive (HR+) metastatic breast cancer (MBC). This review summarizes available data on endocrine therapy for this patient subset and aims to define the most appropriate treatment approach. The combination of luteinizing hormone-releasing hormone (LHRH) agonists plus tamoxifen seems effective and safe and is considered as being superior to either approach alone; still, single-agent therapy remains an acceptable treatment option. Due to their mechanism of action, aromatase inhibitors alone are not suitable for the treatment of premenopausal patients, but the combination with LHRH agonists may result in excellent disease control. Fulvestrant, in conjunction with LHRH agonists, also yields interesting results regarding clinical benefit rate and time to progression; currently, other orally available selective estrogen receptor downregulators are under clinical evaluation. Recently, targeted drugs have been added to ET in order to reverse endocrine resistance, but only limited information regarding their activity in premenopausal patients is available. The cyclin dependent kinase 4 and 6 inhibitor palbociclib when combined with fulvestrant and LHRH agonists was shown to prolong progression-free survival over endocrine therapy alone in pretreated patients; similar results were obtained with the addition of abemacicilib or ribociclib to endocrine therapy. Currently, activity of the mammalian target of rapamycin inhibitor everolimus in combination with letrozole and goserelin is under assessment in premenopausal patients after progression on tamoxifen (MIRACLE trial). IMPLICATIONS FOR PRACTICE:This review provides clinicians with an overview on the available data regarding endocrine treatment of hormone receptor positive (HR+) metastatic breast cancer (MBC) in premenopausal women and summarizes the treatment options available in routine clinical practice. Knowledge of an up-to-date therapeutic approach in women with premenopausal HR+ MBC will lead to better disease management, thereby improving disease control and quality of life while minimizing side effects.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

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