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

Hazel B. Nichols, Mariaelisa Graff, Jeannette T. Bensen, Kathryn L. Lunetta, Katie M. O’Brien, Melissa A. Troester, Lindsay A. Williams, Kristin Young, Chi Chen Hong, Song Yao, Christopher A. Haiman, Edward A. Ruiz-Narváez, Christine B. Ambrosone, Julie R. Palmer, Andrew F. Olshan

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
JournalBreast Cancer Research and Treatment
DOIs
StateAccepted/In press - 2020

Keywords

  • Anti-Müllerian hormone
  • Breast cancer
  • Case–control
  • Genetic polymorphisms

PubMed: MeSH publication types

  • Journal Article

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