Abstract
We conducted gene-based analysis in 26 genes in the FGFR signaling pathway to identify genes carrying genetic variation affecting risk of breast cancer and the specific estrogen receptor (ER) subtypes. Tagging single-nucleotide polymorphisms (SNPs) for each gene were selected and genotyped on a customized Illumina Exome Array. Imputation was carried out using 1000 Genomes haplotypes. The analysis included 3237 SNPs in 3663 breast cancer cases (including 1983 ER-positive, and 1098 ER-negative) and 4687 controls from the African American Breast Cancer Epidemiology and Risk consortium, a collaborative project of four large studies of breast cancer in African American women (Carolina Breast Cancer Study, Black Women’s Health Study, Women’s Circle of Health Study, and Multiethnic Cohort). We used a multi-locus adaptive joint (AdaJoint) test to determine the association of each gene in the FGFR signaling pathway with overall breast cancer and ER subtypes. The FGF1 gene was significantly associated with risk of ER-negative breast cancer (P = 0.001). The FGFR2 gene was associated with risk of overall breast cancer (P = 0.002) and ER-positive breast cancer (P = 0.002). The FGF1 gene affects risk of ER-negative breast cancer in African American women. We confirmed the association of the FGFR2 gene with risk of overall and ER-positive breast cancer. These results highlight the importance of the FGFR signaling pathway in the pathogenesis of breast cancer, and suggest that different genes in the same pathway may be associated with different ER breast cancer subtypes.
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Acknowledgments
We thank participants and staff of the contributing studies. We wish also to acknowledge the late Robert Millikan, DVM, MPH, PhD, who was instrumental in the creation of this consortium. Pathology data were obtained from numerous state cancer registries (Arizona, California, Colorado, Connecticut, Delaware, District of Columbia, Florida, Georgia, Hawaii, Illinois, Indiana, Kentucky, Louisiana, Maryland, Massachusetts, Michigan, New Jersey, New York, North Carolina, Oklahoma, Pennsylvania, South Carolina, Tennessee, Texas, Virginia). The results reported do not necessarily represent their views or the views of the NIH.
Funding
This work was supported by the National Institutes of Health (NIH) P01 CA151135 to C.B. Ambrosone, A.F. Olshan, and J.R. Palmer; NIH R01 CA098663 to J.R. Palmer; NIH R01 CA058420 and UM1 CA164974 to L. Rosenberg; NIH R01 CA100598 to C.B. Ambrosone and E.V. Bandera; NIH UM1 CA164973 and R01 CA54281 to L.N. Kolonel; NIH P50 CA58223 to C. Perou; the U.S. Department of Defense Breast Cancer Research Program, Era of Hope Scholar Award Program grant W81XWH-08-1-0383 to C.A. Haiman; and the University Cancer Research Fund of North Carolina.
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Ruiz-Narváez, E.A., Haddad, S.A., Lunetta, K.L. et al. Gene-based analysis of the fibroblast growth factor receptor signaling pathway in relation to breast cancer in African American women: the AMBER consortium. Breast Cancer Res Treat 155, 355–363 (2016). https://doi.org/10.1007/s10549-015-3672-0
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DOI: https://doi.org/10.1007/s10549-015-3672-0