Pharmacogenetic modulation of combined hormone replacement therapy by progesterone-metabolism genotypes in postmenopausal breast cancer risk

T. R. Rebbeck, A. B. Troxel, S. Norman, G. Bunin, A. DeMichele, R. Schinnar, J. A. Berlin, B. L. Strom

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Combined hormone replacement therapy (CHRT) containing estrogens and progestins is associated with breast cancer risk. The authors evaluated interactions between CHRT use and progestin metabolism genotypes at CYP3A4 and the progesterone receptor (PGR) and their effects on breast cancer risk using the population-based Women's Insights and Shared Experiences (WISE) Study (1999-2002) of postmenopausal Caucasian women (522 breast cancer cases, 708 controls). The authors observed an elevated risk of ductal tumors in women with 3 or more years of CHRT use and PGR 331A alleles compared with those who had neither factor (odds ratio = 3.35, 95% confidence interval (CI): 1.13, 9.99; two-sided pinteraction = 0.035). They also observed an elevated risk of progesterone receptor-positive tumors in women who had had 3 or more years of CHRT use and PGR 331A alleles compared with those who had neither factor (odds ratio = 3.82, 95% CI: 1.26, 11.55; p = 0.028). Finally, they observed an increased risk of estrogen receptor-negative tumors in women without CHRT exposure and CYP3A4*1B alleles compared with those who had neither factor (odds ratio = 6.46, 95% CI: 2.02, 20.66; p = 0.024), although the biologic interpretation of this result requires further study. When stratified by recency of use, PGR effects were observed only in current CHRT users, while CYP3A4 effects were observed only in former CHRT users. Breast cancer risk in women who have used CHRT may be influenced by genetic factors involved in progestin metabolism.

Original languageEnglish (US)
Pages (from-to)1392-1399
Number of pages8
JournalAmerican journal of epidemiology
Volume166
Issue number12
DOIs
StatePublished - Dec 2007

All Science Journal Classification (ASJC) codes

  • Epidemiology

Keywords

  • Breast neoplasms
  • Genotype
  • Hormone replacement therapy
  • Metabolism
  • Pharmacogenetics
  • Postmenopause
  • Progesterone
  • Risk

Fingerprint

Dive into the research topics of 'Pharmacogenetic modulation of combined hormone replacement therapy by progesterone-metabolism genotypes in postmenopausal breast cancer risk'. Together they form a unique fingerprint.

Cite this