Pairwise combinations of estrogen metabolism genotypes in postmenopausal breast cancer etiology

Timothy R. Rebbeck, Andrea B. Troxel, Amy H. Walker, Saarene Panossian, Stephen Gallagher, Ekaterina G. Shatalova, Rebecca Blanchard, Sandra Norman, Greta Bunin, Angela DeMichele, Michelle Berlin, Rita Schinnar, Jesse A. Berlin, Brian L. Strom

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


Estrogen exposures have been associated with breast cancer risk, and genes involved in estrogen metabolism have been reported to mediate that risk. Our goal was to better understand whether combinations of candidate estrogen metabolism genotypes are associated with breast cancer etiology. A population-based case-control study in three counties of the Philadelphia Metropolitan area was undertaken. We evaluated seven main effects and 21 first-order interactions in African Americans and European Americans for genotypes at COMT, CYP1A1, CYP1A2, CYP1B1, CYP3A4, SULT1A1, and SULT1E1 in 878 breast cancer cases and 1,409 matched random digit-dialed controls. In European Americans, we observed main effect associations of genotypes containing any CYP1A1*2C (odds ratio, 1.71; 95% confidence interval, 1.09-2.67) and breast cancer. No significant main effects were observed in African Americans. Three significant first-order interactions were observed. In European Americans, interactions between SULT1A1*2 and CYP1A1*2C genotypes (P interaction < 0.001) and between SULT1E1 and CYP1A2*1F genotypes were observed (Pinteraction = 0.006). In African Americans, an interaction between SULT1A1*2 and CYP1B1*4 was observed (P interaction = 0.041). We applied the false-positive report probability approach, which suggested that these associations were noteworthy; however, we cannot rule out the possibility that chance led to these associations. Pending future confirmation of these results, our data suggest that breast cancer etiology in both European American and African American postmenopausal women may involve the interaction of a gene responsible for the generation of catecholestrogens with a gene involved in estrogen and catecholestrogen sulfation.

Original languageEnglish (US)
Pages (from-to)444-450
Number of pages7
JournalCancer Epidemiology Biomarkers and Prevention
Issue number3
StatePublished - Mar 2007

ASJC Scopus subject areas

  • Epidemiology
  • Oncology


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