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Associations with growth factor genes (FGF1, FGF2, PDGFB, FGFR2, NRG2, EGF, ERBB2) with breast cancer risk and survival: the Breast Cancer Health Disparities Study

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Abstract

Growth factors (GF) stimulate cell proliferation through binding to cell membrane receptors and are thought to be involved in cancer risk and survival. We examined how genetic variation in epidermal growth factor (EGF), neuregulin 2 (NRG2), ERBB2 (HER2/neu), fibroblast growth factors 1 and 2 (FGF1 and FGF2) and its receptor 2 (FGFR2), and platelet-derived growth factor B (PDGFB) independently and collectively influence breast cancer risk and survival. We analyzed data from the Breast Cancer Health Disparities Study which includes Hispanic (2,111 cases, 2,597 controls) and non-Hispanic white (1,481 cases, 1,586 controls) women. Adaptive rank-truncated product (ARTP) analysis was conducted to determine gene significance. Odds ratios (OR) and 95 % confidence intervals were obtained from conditional logistic regression models to estimate breast cancer risk and Cox proportional hazard models were used to estimate hazard ratios (HR) of dying from breast cancer. We assessed Native American (NA) ancestry using 104 ancestry informative markers. We observed few significant associations with breast cancer risk overall or by menopausal status other than for FGFR2 rs2981582. This SNP was significantly associated with ER+/PR+ (OR 1.66, 95 % CI 1.37–2.00) and ER+/PR− (OR 1.54, 95 % CI 1.03–2.31) tumors. Multiple SNPs in FGF1, FGF2, and NRG2 significantly interacted with multiple SNPs in EGFR, ERBB2, FGFR2, and PDGFB, suggesting that breast cancer risk is dependent on the collective effects of genetic variants in other GFs. Both FGF1 and ERBB2 significantly influenced overall survival, especially among women with low levels of NA ancestry (P ARTP = 0.007 and 0.003, respectively). Our findings suggest that genetic variants in growth factors signaling appear to influence breast cancer risk through their combined effects. Genetic variation in ERBB2 and FGF1 appear to be associated with survival after diagnosis with breast cancer.

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Acknowledgments

We would also like to acknowledge the contributions of the following individuals to the study: Sandra Edwards for data harmonization oversight; Erica Wolff and Michael Hoffman for laboratory support; Carolina Ortega for her assistance with data management for the Mexico Breast Cancer Study, Jocelyn Koo for data management for the San Francisco Bay Area Breast Cancer Study, Dr. Tim Byers for his contribution to the 4-Corner’s Breast Cancer Study, and Dr. Josh Galanter for assistance in selection of AIMs markers. The Breast Cancer Health Disparities Study was funded by Grant CA14002 from the National Cancer Institute to Dr. Slattery. The San Francisco Bay Area Breast Cancer Study was supported by Grants CA63446 and CA77305 from the National Cancer Institute, Grant DAMD17-96-1-6071 from the U.S. Department of Defense and Grant 7PB-0068 from the California Breast Cancer Research Program. The collection of cancer incidence data used in this study was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; the National Cancer Institute’s Surveillance, Epidemiology and End Results Program under contract HHSN261201000036C awarded to the Cancer Prevention Institute of California; and the Centers for Disease Control and Prevention’s National Program of Cancer Registries, under agreement #1U58 DP000807-01 awarded to the Public Health Institute. The 4-Corner’s Breast Cancer Study was funded by Grants CA078682, CA078762, CA078552, and CA078802 from the National Cancer Institute. The research also was supported by the Utah Cancer Registry, which is funded by contract N01-PC-67000 from the National Cancer Institute, with additional support from the State of Utah Department of Health, the New Mexico Tumor Registry, and the Arizona and Colorado cancer registries, funded by the Centers for Disease Control and Prevention National Program of Cancer Registries and additional state support. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official view of the National Cancer Institute or endorsement by the State of California Department of Public Health, the National Cancer Institute, and the Centers for Disease Control and Prevention or their Contractors and Subcontractors. The Mexico Breast Cancer Study was funded by Consejo Nacional de Ciencia y Tecnología (CONACyT) (SALUD-2002-C01-7462).

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Authors and Affiliations

  1. Department of Medicine, University of Utah, 383 Colorow, Salt Lake City, UT, 84108, USA

    Martha L. Slattery, Jennifer Herrick, Abbie Lundgreen & Roger K. Wolff

  2. Cancer Prevention Institute of California, Fremont, CA, 94538, USA

    Esther M. John

  3. Division of Epidemiology, Department of Health Research and Policy and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, 94305, USA

    Esther M. John

  4. Department of Preventive Medicine, Keck School of Medicine of USC, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, 90089, USA

    Mariana C. Stern

  5. Cancer Prevention and Control, Moffitt Cancer Center, Tampa, FL, 33612, USA

    Anna R. Giuliano

  6. Department of Biology, University of Colorado at Colorado Springs, 1420 Austin Bluffs Parkway, Colorado Springs, CO, 80918, USA

    Lisa Hines

  7. Department of Epidemiology and Population Health, School of Public Health & Information Sciences, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, 40292, USA

    Kathy B. Baumgartner

  8. Centro de Investigación en Salud Poblacional, Instituto Nacional de Salud Pública, Av. Universidad No. 655 Col. Sta. Ma. Ahuacatitlán, CP 62100, Cuernavaca, Morelos, Mexico

    Gabriela Torres-Mejia

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  1. Martha L. Slattery
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Correspondence to Martha L. Slattery.

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Slattery, M.L., John, E.M., Stern, M.C. et al. Associations with growth factor genes (FGF1, FGF2, PDGFB, FGFR2, NRG2, EGF, ERBB2) with breast cancer risk and survival: the Breast Cancer Health Disparities Study. Breast Cancer Res Treat 140, 587–601 (2013). https://doi.org/10.1007/s10549-013-2644-5

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