Zhong Xuan, Luo Meihua, Wu Yanmei, Zhou Xinfeng, Yu Xinfa, Liu Li, Chen Sidong
Department of Tumor, Injury and Nutrition, Shenzhen Nanshan Center for Chronic Disease Control, Shenzhen, Guangdong, China.
Department of Epidemiology and Biostatistics, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China.
Cancer Biomark. 2021;32(1):3-9. doi: 10.3233/CBM-203162.
A recent genome-wide association study (GWAS) has posed STAT4 as a promising susceptibility gene for hepatocellular carcinoma (HCC). However, the most significant variant in this GWAS, rs7574865, yielded inconsistent results.
This study, in a Southern Chinese population, was aimed to clarify the roles in HCC incidence of the rs7574865 and other two potentially functional variants, rs897200 and rs1031507 in STAT4.
This study enrolled 631 new HCC cases and 631 cancer-free controls. The genetic association was estimated using the multivariate logistic regression model. The pairwise gene-environment interactions were assessed using the multiplicative term in regression model and the "Delta" method for the additive scale.
In the multivariate analysis, the rs7574865 TT genotype conferred a decreased risk of HCC compared to the GG genotype (adjusted OR = 0.62, 95%CI = 0.38∼0.99). The significant association of rs7574865 was also observed under the additive genetic model, with an adjusted OR of 0.81 (95%CI = 0.65∼0.99). Nevertheless, other two variants alone showed no significant association, as well as the haplotypes and genetic risk scores. Further analysis indicated a potential interaction between the rs897200 and alcohol drinking (P= 0.048 and 0.072 for additive and multiplicative interactions, respectively). Drinkers with the rs897200 CT+CC genotypes presented an increased disease-risk, as compared with non-drinkers carrying the TT genotype (adjusted OR = 1.68, 95%CI = 1.11∼2.54).
The variant in STAT4, rs7574865, serves as a potential marker for predicting incidence of HCC. The rs897200 variant possibly interplays with alcohol drinking to alter HCC risk in the Southern Chinese, but warrants further investigation.
最近一项全基因组关联研究（GWAS）将信号转导和转录激活因子4（STAT4）定位为肝细胞癌（HCC）一个有前景的易感基因。然而，该GWAS中最显著的变异位点rs7574865却得出了不一致的结果。
在华南人群中开展本研究，旨在明确rs7574865以及STAT4基因中另外两个潜在功能性变异位点rs897200和rs1031507在HCC发病中的作用。
本研究纳入631例新发HCC病例和631例无癌对照。采用多因素logistic回归模型估计遗传关联性。使用回归模型中的相乘项和相加尺度的“Delta”法评估基因-环境的两两相互作用。
在多因素分析中，与GG基因型相比rs7574865的TT基因型使HCC风险降低（校正比值比=0.62，95%置信区间=0.38∼0.99）。在加性遗传模型下也观察到rs7574865的显著关联性，校正比值比为0.81（95%置信区间=0.65∼0.99）。然而，另外两个变异位点单独分析未显示出显著关联性，单倍型和遗传风险评分分析也是如此。进一步分析表明rs897200与饮酒之间存在潜在相互作用（相加和相乘相互作用的P值分别为0.048和0.072）。与携带TT基因型的非饮酒者相比，携带rs897200 CT+CC基因型的饮酒者疾病风险增加（校正比值比=1.68，95%置信区间=1.11∼2.54）。
STAT基因中的变异位点rs7574865可作为预测HCC发病的潜在标志物。rs897200变异位点可能与饮酒相互作用，从而改变华南人群的HCC风险，但仍需进一步研究。
