Although genome-wide association studies (GWAS) have identified sixteen risk loci for endometrial cancer, identifying prospective susceptibility genes remains difficult.
Researchers used the largest endometrial cancer GWAS and gene expression from six relevant tissues to perform transcriptome-wide association study (TWAS) analyses, prioritizing eight candidate endometrial cancer susceptibility genes, one of which (EEFSEC) was located at a potentially novel endometrial cancer risk locus. They also found evidence of CYP19A1 (adipose), HEY2 (ovary), and SKAP1 tissue-specific expression correlations. A phenome-wide association analysis found relationships between potential susceptibility genes and endometrial cancer risk variables such as anthropometric, cardiovascular, diabetes, bone health, and sex hormone characteristics.
Finally, TWAS data analysis identifies promising drugs for endometrial cancer repurposing. In summary, this work identifies endometrial cancer susceptibility genes, including those with evidence of tissue specificity, shedding light on endometrial cancer etiology and opening up new possibilities for treatment development.