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Genetic variants in anti-Müllerian hormone-related genes and breast cancer risk: results from the AMBER consortium

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

Circulating anti-Müllerian hormone (AMH) levels are positively associated with time to menopause and breast cancer risk. We examined breast cancer associations with single nucleotide polymorphisms (SNPs) in the AMH gene or its receptor genes, ACVR1 and AMHR2, among African American women.

Methods

In the AMBER consortium, we tested 65 candidate SNPs, and 1130 total variants, in or near AMH, ACVR1, and AMHR2 and breast cancer risk. Overall, 3649 cases and 4230 controls contributed to analyses. Odds ratios (OR) and 95% confidence intervals (CI) for breast cancer were calculated using multivariable logistic regression.

Results

After correction for multiple comparisons (false-discovery rate of 5%), there were no statistically significant associations with breast cancer risk. Without correction for multiple testing, four candidate SNPs in ACVR1 and one near AMH were associated with breast cancer risk. In ACVR1, rs13395576[C] was associated with lower breast cancer risk overall (OR 0.84; 95% CI 0.72, 0.97) and for ER+ disease (OR 0.75; CI 0.62, 0.89) (p < 0.05). Rs1220110[A] and rs1220134[T] each had ORs of 0.89–0.90 for postmenopausal and ER+ breast cancer (p ≤ 0.03). Conversely, rs1682130[T] was associated with higher risk of ER+ breast cancer (OR 1.17; 95% CI 1.04, 1.32). Near AMH, rs6510652[T] had ORs of 0.85–0.90 for breast cancer overall and after menopause (p ≤ 0.02).

Conclusions

The present results, from a large study of African American women, provide limited support for an association between AMH-related polymorphisms and breast cancer risk and require replication in other studies.

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Acknowledgements

The authors appreciate the helpful comments of Drs. Alexandra White and Helen Chin.

Funding

This research was funded in part by the National Center for Advancing Translational Sciences (KL2-TR001109) and by the National Institutes of Health: P01 CA151135 (CBA, JRP, and AFO), UM1 CA164974 (JRP), R01 CA098663 (JRP), R01 CA100598 (CBA), P50 CA58223 (MAT, AO), U01 CA179715 (MAT); and by the Susan G. Komen Foundation (JRP), the Breast Cancer Research Foundation (CBA); and the University Cancer Research Fund of North Carolina. The results do not necessarily reflect the views of the NIH or the sponsors, who had no role in study design; data collection, analysis, or interpretation; or writing and submission of the manuscript.

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Authors and Affiliations

  1. Department of Epidemiology, University of North Carolina Gillings School of Global Public Health, 2104F McGavran-Greenberg Hall, Chapel Hill, NC, 27599-7435, USA

    Hazel B. Nichols, Mariaelisa Graff, Jeannette T. Bensen, Melissa A. Troester, Kristin Young & Andrew F. Olshan

  2. Slone Epidemiology Center, Boston University, 72 E Concord Street, Boston, MA, 02118, USA

    Kathryn L. Lunetta & Julie R. Palmer

  3. Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, NC, USA

    Katie M. O’Brien

  4. Department of Pediatrics, University of Minnesota, 2450 Riverside Avenue, Minneapolis, MN, 55454, USA

    Lindsay A. Williams

  5. Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, NY, 14263, USA

    Chi-Chen Hong, Song Yao & Christine B. Ambrosone

  6. Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA, USA

    Christopher A. Haiman

  7. Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA

    Edward A. Ruiz-Narváez

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  1. Hazel B. Nichols
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  2. Mariaelisa Graff
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  9. Chi-Chen Hong
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  13. Christine B. Ambrosone
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  15. Andrew F. Olshan
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Correspondence to Hazel B. Nichols.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Nichols, H.B., Graff, M., Bensen, J.T. et al. Genetic variants in anti-Müllerian hormone-related genes and breast cancer risk: results from the AMBER consortium. Breast Cancer Res Treat 185, 469–478 (2021). https://doi.org/10.1007/s10549-020-05944-4

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  • DOI: https://doi.org/10.1007/s10549-020-05944-4

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