Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
State-Level Model Center of Experimental Teaching, Department of Hygienic Analysis and Detection, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
Cancer Epidemiol. 2014 Aug;38(4):414-8. doi: 10.1016/j.canep.2014.03.013. Epub 2014 May 3.
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.
癌症睾丸（CT）基因主要在睾丸中表达，并在广泛的癌症中异位激活。CT 抗原的表达已被证明显著影响非小细胞肺癌（NSCLC）患者的生存。最近，全基因组关联研究（GWAS）和表达分析确定了一个与汉族人群肺癌风险相关的新 CT 基因（HORMAD2）。因此，本研究旨在评估 HORMAD2 多态性在汉族晚期 NSCLC 患者一线铂类化疗中的潜在预后价值。
我们选择了 8 个具有影响转录因子结合功能的 HORMAD2 单核苷酸多态性（SNP），并使用 MassARRAY 平台对 303 名晚期 NSCLC 患者进行了这些 SNP 的基因分型。所有患者均接受一线铂类化疗，但未接受手术治疗。使用对数秩检验和 Cox 比例风险模型进行生存分析。
HORMAD2 中的 4 个 SNP（rs9620953、rs8135823、rs5753025 和 rs9625921）与晚期 NSCLC 患者的生存显著相关。其中，与 C 等位基因相比，携带 rs9620953 T 等位基因的患者死亡风险显著降低（加性模型：HR，0.53，95%CI，0.32-0.89，P=0.016；显性模型：HR，0.50，95%CI，0.29-0.84，P=0.010）。同样，与 T 等位基因相比，rs8135823 中的 G 等位基因也可以降低 NSCLC 患者的死亡风险（加性模型：HR，0.63，95%CI，0.41-0.95，P=0.028；显性模型：HR，0.60，95%CI，0.39-0.93，P=0.022）。此外，在不同的遗传模型中，rs5753025 的 C 等位基因和 rs9625921 的 G 等位基因也降低了 NSCLC 的死亡风险（rs5753025 的加性模型：HR，0.80，95%CI，0.65-0.98，P=0.032；rs9625921 的杂合模型：HR，0.71，95%CI，0.51-0.99，P=0.040）。在联合效应分析中，我们发现与不携带任何等位基因的患者相比，携带一个、两个和三个至八个有利等位基因的患者生存更好。
这些发现表明，CT 基因 HORMAD2 的多态性可能与汉族晚期 NSCLC 的预后有关。需要进一步的大型和功能研究来证实这些结果。
