Evaluation of genetic variants in autophagy pathway genes as prognostic biomarkers for breast cancer

Autophagy-related genes (ATGs) play a critical role in the development of various diseases including cancer. However, the role of ATGs in breast cancer survival remains unclear. This study aims to investigate whether genetic variants in core ATGs are correlated with the prognosis of breast cancer. A total of 14 potentially functional variants in core ATGs were genotyped in 790 breast cancer patients. The association of each variant with breast cancer-specific survival was evaluated by log-rank test and Cox regression model. In silico analysis was also performed to evaluate the potential function of selected variants. We found that one variant in ATG7 rs8154 (A > G) was significantly associated with breast cancer-specific survival after adjusted for age and clinical stage (HR = 1.61, 95% CI: 1.12-2.31, P = 0.010). Stratified analysis showed that the prognostic role of rs8154 was significant in subgroups of elder age, elder menarche age, and postmenopausal status (all P < 0.001). Interaction effects were also detected between rs8154 and these grouping variables. In silico analysis revealed that rs8154 was annotated to be expression quantitative trait loci (eQTL) and methylation quantitative trait loci (meQTL) based on Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) datasets (both P < 0.05). In addition, upregulated expression of ATG7 in breast cancer tissues was observed and is significantly associated with poorer overall survival (log-rank P = 0.015), poorer relapse free survival (log-rank P = 0.017), and poorer distant metastasis free survival (log-rank P = 0.034) in different datasets. Summarily, ATG7 variant rs8154 represents a novel prognostic marker for breast cancer patients, which may shed light on clinical risk stratification and therapeutic decision making.