Association of estrogen receptor α polymorphisms with breast cancer risk in older Caucasian women

Authors


  • Investigators in the Study of Osteoporotic Fractures Research Group. University of California, San Francisco (Coordinating Center:) S.R. Cummings (principal investigator), K.L. Stone (co-investigator), D.C. Bauer (co-investigator), M.C. Nevitt (co-investigator), W. Browner, (co-investigator), D.M. Black (study statistician), H.K. Genant (director, central radiology laboratory), R. Benard, T. Blackwell, M. Dockrell, S. Ewing, C. Fox, R. Fullman, D. Kimmel, S. Litwack, L.Y. Lui, J. Maeda, P. Mannen, L. Nusgarten, L. Palermo, M. Rahorst, C. Schambach, J. Schneider, R. Scott, D. Tanaka, C. Yeung; University of Maryland: M.C. Hochberg (principal investigator), L. Makell, (project director), R. Nichols, C. Boehm, L. Finazzo, T. Page, S. Trusty, B. Whitkop; University of Minnesota: K.E. Ensrud (principal investigator), K. Margolis (co-investigator), P. Schreiner (co-investigator), K. Worzala (co-investigator), S. Love (clinical research director), E. Mitson (clinic coordinator), C. Bird, D. Blanks, F. Imker-Witte, K. Jacobson, K. Knauth, N. Nelson, E. Penland-Miller, G. Saecker; University of Pittsburgh: J.A. Cauley (principal investigator), L.H. Kuller (co-principal investigator), M. Vogt (co-investigator), L. Harper (project director), L. Buck (clinic coordinator), C. Bashada, D. Cusick, G. Engleka, A. Flaugh, A. Githens, M. Gorecki, D. Medve, M. Nasim, C. Newman, S. Rudovsky, N. Watson, D. Lee; The Kaiser Permanente Center for Health Research, Portland, Oregon: T. Hillier (principal investigator), E. Harris (co-principal investigator), E. Orwoll (co-investigator), H. Nelson (co-investigator), M. Aiken (biostatistician), J. Van Marter (project administrator), M. Rix (clinic coordinator), J. Wallace, K. Snider, K. Canova, K. Pedula, J. Rizzo.

Abstract

Estrogens exert their effect on the breast through the estrogen receptor. We prospectively investigated breast cancer risk associated with 2 polymorphic sites in the estrogen receptor alpha gene (ESR1). A total of 4,248 Caucasian women from the Study of Osteoporotic Fractures were genotyped for the −401 T/C and −354 A/G polymorphisms in ESR1. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the associations between genotypes and breast cancer. During a mean follow-up of 12.4 years, 252 (5.9%) women developed breast cancer. The HR (95% CI) for breast cancer were 0.928 (0.708, 1.22) and 0.834 (0.538, 1.29) for the −354 A/G and A/A genotypes, respectively. Interactions with −354 variant were observed for smoking (HR = 1.52 and 1.56 for A/G and A/A smokers, respectively; HR = 0.74 and 0.60 for A/G and A/A non-smokers, respectively; interaction p = 0.03) and walking (HR = 0.75 and 1.15 for A/G and A/A walkers, respectively; HR = 0.18 and 0.49 for A/G and A/A non-walkers, respectively; interaction p = 0.01). There were no differences in the HR for the −401 T/C genotypes. An interaction between parity and carriage of the T allele was found (HR = 0.60 vs. 1.12 for nulliparous vs. parous women; interaction p = 0.03). ESR1 polymorphisms in combination with lifestyle factors may be associated with breast cancer risk in older Caucasian women. © 2005 Wiley-Liss, Inc.

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