Wu Meei-Maan, Hsieh Fang-I, Hsu Ling-I, Lee Te-Chang, Chiou Hung-Yi, Chen Chien-Jen
Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, 11031 Taipei, Taiwan.
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, 11031 Taipei, Taiwan.
J Clin Med. 2021 Apr 3;10(7):1489. doi: 10.3390/jcm10071489.
The induction of heme oxygenase-1 (HO-1) has been shown to have therapeutic potential in experimental models of hepatitis and liver fibrosis, which are closely related to liver cancer. In humans, HO-1 induction is transcriptionally modulated by the length of a GT-repeat [(GT)n] in the promoter region. We aimed to investigate the effect of HO-1 (GT)n variants on liver cancer in a human population. We determined the HO-1 genotype in 1153 study subjects and examined their association with liver cancer risk during a 15.9-year follow-up. Allelic polymorphisms were classified as short [S, <27 (GT)n] or long [L, ≥27 (GT)n]. Newly developed cancer cases were identified through linkage to the National Cancer Registry of Taiwan. Multivariate Cox regression analysis was used to evaluate the effect of the HO-1 (GT)n variants. Alpha-fetoprotein (AFP) and cirrhosis history were also examined. The S/S genotype was found to be significantly associated with liver cancer risk, compared to the L/S and L/L genotypes. The S/S genotype group also had a higher percentage of subjects with abnormal AFP levels than other groups. There were significant percentages of cirrhosis among groups who carried S-alleles. Our findings indicate that short (GT)n variants in the HO-1 gene may confer susceptibility to rather than protection from liver cirrhosis/cancer.
血红素加氧酶-1（HO-1）的诱导在与肝癌密切相关的肝炎和肝纤维化实验模型中已显示出治疗潜力。在人类中，HO-1的诱导受启动子区域GT重复序列[(GT)n]长度的转录调控。我们旨在研究HO-1 (GT)n变异体在人群中对肝癌的影响。我们确定了1153名研究对象的HO-1基因型，并在15.9年的随访期间检查了它们与肝癌风险的关联。等位基因多态性被分类为短[S，<27 (GT)n]或长[L，≥27 (GT)n]。通过与台湾国家癌症登记处的链接确定新发生的癌症病例。采用多变量Cox回归分析来评估HO-1 (GT)n变异体的作用。还检查了甲胎蛋白（AFP）和肝硬化病史。与L/S和L/L基因型相比，发现S/S基因型与肝癌风险显著相关。S/S基因型组中AFP水平异常的受试者百分比也高于其他组。携带S等位基因的组中肝硬化的百分比也很高。我们的研究结果表明，HO-1基因中的短(GT)n变异体可能会使人易患肝硬化/癌症，而不是起到保护作用。
