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Cited by 24Digital Radiography and Breast ImagingGenetic Associations and EpidemiologyEstrogen and related hormone effects

A comprehensive evaluation of interaction between genetic variants and use of menopausal hormone therapy on mammographic density

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Rudolph, Anja, Fasching, Peter A., Behrens, Sabine, Eilber, Ursula, Bolla, Manjeet K., Wang, Qin, Thompson, Deborah, Czene, Kamila +32 more·2015·Breast Cancer Research
DOI 10.1186/s13058-015-0625-9PMC PMC4537547
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Abstract

INTRODUCTION: Mammographic density is an established breast cancer risk factor with a strong genetic component and can be increased in women using menopausal hormone therapy (MHT). Here, we aimed to identify genetic variants that may modify the association between MHT use and mammographic density. METHODS: The study comprised 6,298 postmenopausal women from the Mayo Mammography Health Study and nine studies included in the Breast Cancer Association Consortium. We selected for evaluation 1327 single nucleotide polymorphisms (SNPs) showing the lowest P-values for interaction (P int) in a meta-analysis of genome-wide gene-environment interaction studies with MHT use on risk of breast cancer, 2541 SNPs in candidate genes (AKR1C4, CYP1A1-CYP1A2, CYP1B1, ESR2, PPARG, PRL, SULT1A1-SULT1A2 and TNF) and ten SNPs (AREG-rs10034692, PRDM6-rs186749, ESR1-rs12665607, ZNF365-rs10995190, 8p11.23-rs7816345, LSP1-rs3817198, IGF1-rs703556, 12q24-rs1265507, TMEM184B-rs7289126, and SGSM3-rs17001868) associated with mammographic density in genome-wide studies. We used multiple linear regression models adjusted for potential confounders to evaluate interactions between SNPs and current use of MHT on mammographic density. RESULTS: No significant interactions were identified after adjustment for multiple testing. The strongest SNP-MHT interaction (unadjusted P int <0.0004) was observed with rs9358531 6.5kb 5' of PRL. Furthermore, three SNPs in PLCG2 that had previously been shown to modify the association of MHT use with breast cancer risk were found to modify also the association of MHT use with mammographic density (unadjusted P int <0.002), but solely among cases (unadjusted P int SNP×MHT×case-status <0.02). CONCLUSIONS: The study identified potential interactions on mammographic density between current use of MHT and SNPs near PRL and in PLCG2, which require confirmation. Given the moderate size of the interactions observed, larger studies are needed to identify genetic modifiers of the association of MHT use with mammographic density.

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  • PLCγ2 SNPs were identified as breast cancer risk factors in patients on menopausal hormone replacement therapy.

    “Indeed, PLCγ2 SNPs were identified as breast cancer risk factors in patients on menopausal hormone replacement therapy (152, 153).”

    From The role of PLCγ2 in immunological disorders, cancer, and neurodegeneration (2021) · cites this paper as [152]

    The Abstract Results and Discussion say that three PLCG2 SNPs had previously shown potential interaction with menopausal hormone therapy (MHT) use in relation to breast cancer risk. This supports an MHT-related risk association, but describing the SNPs as established breast cancer risk factors overstates the finding; this paper primarily tests their interaction with MHT use on mammographic density. No page numbers are available in our copy. (LLM, conf=0.86)

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Cited by

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Authors
Rudolph, A., Fasching, P. A., Behrens, S., Eilber, U., Bolla, M. K., Wang, Q., Thompson, D., Czene, K., Brand, J. S., Li, J., Scott, C., Pankratz, V. S., Brandt, K., Hallberg, E., Olson, J. E., Lee, A., Beckmann, M. W., Ekici, A. B., Haeberle, L., Maskarinec, G., Le Marchand, L., Schumacher, F., Milne, R. L., Knight, J. A., Apicella, C., Southey, M. C., Kapuscinski, M. K., Hopper, J. L., Andrulis, I. L., Giles, G. G., Haiman, C. A., Khaw, K.-T., Luben, R., Hall, P., Pharoah, P. D. P., Couch, F. J., Easton, D. F., dos-Santos-Silva, I., Vachon, C., & Chang-Claude, J.
Affiliations
  • German Cancer Research Center (DE)
  • University of California, Los Angeles (US)
  • University of Cambridge (GB)
  • Karolinska Institutet (SE)
  • Mayo Clinic (US)
  • Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
  • University of Hawaii Cancer Center (US)
  • University of Southern California (US)
  • The University of Melbourne (AU)
  • Mount Sinai Hospital (CA)
Corresponding author
Rudolph, Anja
ORCID
Venue
Breast Cancer Research
Publisher
Springer Science and Business Media LLC
Published
2015-08-16
Volume
17
Issue
1
Pages
110-110
ISSN
  • 1465-5411 (ISSN-L)
  • 1465-542X
DOI
10.1186/s13058-015-0625-9
PMC
PMC4537547
OpenAlex
W2135800416
Cited by
24
References
3
Citations by year
2026: 2 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 3 · 2020: 4 · 2019: 3 · 2018: 3 · 2017: 1 · 2016: 1
FWCI
0.30
Type
journal article
Language
en
Open access
Licence
Locations
  • Breast Cancer Research (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
  • Minerva Access (University of Melbourne) (submittedVersion, cc-by)
  • TSpace (University of Toronto) (submittedVersion)
  • National University of Singapore (submittedVersion, cc-by)
  • OPUS FAU (Kooperativer Bibliotheksverbund Berlin-Brandenburg (KOBV), on behalf of the Universitätsbibliothek Erlangen-Nürnberg) (submittedVersion, cc-by)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
Funders
  • Seventh Framework Programme (HEALTH-F2-2009-223175)
  • Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565, C1287/A10118, C1287/8459)
  • National Institutes of Health (CA128978, 1U19 CA148537, 1U19 CA148065, 1U19 CA148112, CA128978, CA116167, CA176785, CA116201, CA63464, CA54281, CA098758, CA132839, R01 CA128931, R01 CA140286, R01 CA97396, P50 CA116201, R01 CA177150)
  • US Department of Defence (W81XWH-10-1-0341)
  • Canadian Institutes of Health Research
  • Komen Foundation for the Cure
  • Breast Cancer Research Foundation
  • Ovarian Cancer Research Fund
  • National Cancer Institute (UM1 CA164920)
  • National Health and Medical Research Council (209057, 251553, 504711)
  • New South Wales Cancer Council
  • Victorian Health Promotion Foundation
  • Victorian Breast Cancer Research Consortium
  • University Hospital of Erlangen (ELAN)
  • Medical Research Council
  • Stroke Association
  • British Heart Foundation
  • Department of Health
  • Research into Ageing
  • Academy of Medical Sciences
  • Agency for Science, Technology and Research of Singapore
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Digital Radiography and Breast Imaging
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Keywords
breast density, hormone replacement therapy, gene-environment interaction, single nucleotide polymorphisms, breast cancer risk, postmenopausal women, PLCγ2, PRL, ESR2, CYP1A1, breast cancer susceptibility genes, genetic variants, breast cancer risk prediction models, Breast Cancer Association Consortium
MeSH terms
Breast Density, Aged, Aged, 80 and over, Breast, Breast Neoplasms, Female, Humans, Mammography, Middle Aged, Risk Factors, Case-Control Studies, Postmenopause, Hormone Replacement Therapy, Polymorphism, Single Nucleotide, Mammary Glands, Human, Genome-Wide Association Study

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