DNA methylation associations with cognitive function in early-stage hormone receptor-positive breast cancer patients

Approximately one-third of breast cancer (BC) patients show poorer cognitive function (CF). Using DNA methylation (DNAm) data, here we aimed to identify genes and biological pathways associated with CF in postmenopausal women with early-stage hormone receptor-positive (HR+) BC.

Epigenome-wide association studies (EWAS) and differentially methylated region analyses were performed for each CF phenotype (seven objective domains and one subjective phenotype) using DNAm data from whole blood samples (n = 109) taken at the time of enrollment.

When adjusting for age, verbal IQ scores, and global DNAm signature, cg10331779 near CTNND2 (p-value = $9.65\times {10}^{-9}$) and cg25906741 in MLIP (p-value = $2.01\times {10}^{-8}$) were associated with processing speed and subjective CF, respectively, while regions in/near SLC6A11, PRKG1/CSTF2T, and FAM3B for processing speed, and regions in/near PI4KB and SGCE/PEG10 for mental flexibility were differentially methylated. In addition, beta-estradiol was identified as a common upstream regulator for all the CF phenotypes, suggesting an essential role of estrogen in explaining variation in CF of HR+ BC patients.

In our EWAS of 8 CF phenotypes, we found two epigenome-wide significant signals, one for processing speed and the other for subjective CF. We also found three differentially methylated regions associated with processing speed and two associated with mental flexibility.

www.clinicaltrials.gov identifier is NCT02793921.