Identification of a rat mammary tumor risk locus that is syntenic with the commonly amplified 8q12.1 and 8q22.1 regions in human breast cancer patients

Breast cancer risk is ~31\% heritable, yet the majority of the underlying risk factors remain poorly defined. Here, we used F2-linkage analysis in a rat mammary tumor model to identify a novel 11.2 Mb modifier locus of tumor incidence and burden on rat chromosome 5 (chr5: 15.4 – 26.6 Mb). Genomic and RNA sequencing analysis identified four differentially expressed candidates: TMEM68, IMPAD1, SDCBP, and RBM12B. Analysis of the human syntenic candidate region revealed that SDCBP is in close proximity to a previously reported genetic risk locus for human breast cancer. Moreover, analysis of the candidate genes in The Cancer Genome Atlas (TCGA) revealed that they fall within the commonly amplified 8q12.1 and 8q22.1 regions in human breast cancer patients and are correlated with worse overall survival. Collectively, this study presents novel evidence suggesting that TMEM68, IMPAD1, SDCBP, and RBM12B are modifiers of human breast cancer risk and outcome.