ATG12 expression quantitative trait loci associated with head and neck squamous cell carcinoma risk in a Chinese Han population

Autophagy is an essential process to maintain cellular homeostasis and functions, which has been demonstrated to play an important role in the different stages of tumorigenesis. To evaluate whether the genetic variants in autophagy-related genes influence the head and neck squamous cell carcinoma (HNSCC) risk, we conducted a case-control study to analyze 11 tagging single nucleotide polymorphisms (SNPs) of three core autophagosome formation genes (ATG5, ATG12, and ATG16L1) with 576 HNSCC cases and 1552 healthy controls among Chinese population. Finally, we identified that rs26537 of ATG12 (additive model: adjusted odds ratio [OR]=1.19, 95% confidence interval [CI]=1.03-1.37, P=0.017) and rs4663402 in ATG16L1 (additive model: adjusted OR=1.39, 95%CI=1.08-1.80, P=0.010) were significantly associated with the increased risk of HNSCC. However, no association was detected between other SNPs and HNSCC risk. The results of expression quantitative trait loci (eQTL) analysis based on Genotype-Tissue Expression (GTEx) accessible data, showed that the risk allele of rs26537 was significantly associated with up-regulated expression of ATG12 (P=0.0021). Further luciferase activity assay indicated that rs26537 T>C in ATG12 intron one region significantly enhanced transcription activity. These results suggested that ATG12 eQTL SNP rs26537 might contribute to an allele-specific effect on the expression of host gene ATG12 and explain a fraction of HNSCC genetic susceptibility.