title: Pairwise combinations of estrogen metabolism genotypes in postmenopausal breast cancer etiology.
abstract: 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 (P(interaction) = 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.
authors: Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, 904 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104-6021, USA. trebbeck@cceb.med.upenn.edu
authors: Timothy R
authors: TR
authors: Rebbeck
authors: Andrea B
authors: AB
authors: Troxel
authors: Amy H
authors: AH
authors: Walker
authors: Saarene
authors: S
authors: Panossian
authors: Stephen
authors: S
authors: Gallagher
authors: Ekaterina G
authors: EG
authors: Shatalova
authors: Rebecca
authors: R
authors: Blanchard
authors: Sandra
authors: S
authors: Norman
authors: Greta
authors: G
authors: Bunin
authors: Angela
authors: A
authors: DeMichele
authors: Michelle
authors: M
authors: Berlin
authors: Rita
authors: R
authors: Schinnar
authors: Jesse A
authors: JA
authors: Berlin
authors: Brian L
authors: BL
authors: Strom
mesh_terms: D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism*; D016022:Case-Control Studies; D004967:Estrogens / Q000378:metabolism*; D005006:Ethnicity; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008875:Middle Aged; D010414:Pennsylvania / Q000453:epidemiology; D011159:Population Surveillance; D017698:Postmenopause; D012042:Registries
chemical_list: D004967:Estrogens