Association of polymorphisms at HORMAD2 and prognosis in advanced non-small-cell lung cancer patients

Cancer-testis (CT) genes are predominantly expressed in the testis and are ectopically activated in a wide range of cancers. The expression of CT antigens has been shown to significantly affect the survival of patients with non-small-cell lung cancer (NSCLC). Recently, a genome-wide association study (GWAS) and expression analysis have identified a novel CT gene (HORMAD2) associated with lung cancer risk in Han Chinese people. Thus, the aim of this study is to evaluate the potential prognostic value of HORMAD2 polymorphisms in Han Chinese patients with advanced NSCLC and undergoing first-line platinum-based chemotherapy.

We selected eight single-nucleotide polymorphisms (SNPs) of HORMAD2 with the potential function of affecting the binding of transcription factors, and we genotyped these SNPs in 303 patients with advanced NSCLC using the MassARRAY platform. All patients were treated with first-line platinum-based chemotherapy but without surgery. Log-rank test and Cox proportional hazard models were used for the survival analyses.

Four SNPs at HORMAD2 (rs9620953, rs8135823, rs5753025 and rs9625921) were significantly associated with the survival of advanced NSCLC patients. Among these, patients with the rs9620953 T allele had a significantly reduced risk of death compared to those with the C allele (additive model: HR, 0.53, 95%CI, 0.32-0.89, P=0.016; dominant model: HR, 0.50, 95%CI, 0.29-0.84, P=0.010). Similarly, the G allele at rs8135823 could decrease the death risk of NSCLC patients compared to the T allele (additive model: HR, 0.63, 95%CI, 0.41-0.95, P=0.028; dominant model: HR, 0.60, 95%CI, 0.39-0.93, P=0.022). Furthermore, both the rs5753025 C allele and the rs9625921 G allele also decreased the death risk in NSCLC in different genetic models (additive model for rs5753025: HR, 0.80, 95%CI, 0.65-0.98, P=0.032; heterozygote model for rs9625921: HR, 0.71, 95%CI, 0.51-0.99, P=0.040). In the joint effect analyses, we found that patients with one, two, and three to eight favorable alleles had a better survival compared with patients carrying no alleles.

These findings indicate that polymorphisms at the CT gene HORMAD2 might be involved in the prognosis of advanced NSCLC in Han Chinese. Further larger and functional studies are needed to confirm the results.