Abstracto
- We conducted gene-based analysis in 26 genesin the FGFR signaling pathway to identify genes carryinggenetic variation affecting risk of breast cancer and thespecific estrogen receptor (ER) subtypes. Tagging single-nucleotide polymorphisms (SNPs) for each gene wereselected and genotyped on a customized Illumina ExomeArray. Imputation was carried out using 1000 Genomeshaplotypes. The analysis included 3237 SNPs in 3663breast cancer cases (including 1983 ER-positive, and 1098ER-negative) and 4687 controls from the African Ameri-can Breast Cancer Epidemiology and Risk consortium, acollaborative project of four large studies of breast cancerin African American women (Carolina Breast CancerStudy, Black Women’s Health Study, Women’s Circle ofHealth Study, and Multiethnic Cohort). We used a multi-locus adaptive joint (AdaJoint) test to determine theassociation of each gene in the FGFR signaling pathwaywith overall breast cancer and ER subtypes. The FGF1gene was significantly associated with risk of ER-negativebreast cancer (P=0.001). The FGFR2 gene was associ-ated with risk of overall breast cancer (P=0.002) and ER-positive breast cancer (P=0.002). The FGF1 gene affectsrisk of ER-negative breast cancer in African Americanwomen. We confirmed the association of the FGFR2 genewith risk of overall and ER-positive breast cancer. Theseresults highlight the importance of the FGFR signalingpathway in the pathogenesis of breast cancer, and suggestthat different genes in the same pathway may be associatedwith different ER breast cancer subtypes.