INTS10遗传变异及基因-环境交互作用对HBV相关肝癌病理特征的影响

目的 探讨INTS10遗传变异及基因-环境交互作用对HBV相关肝癌病理特征的影响。方法 募集705例新发HBV相关肝癌病例，对INTS10的4个遗传变异（rs4268139、rs4599828、rs7822495和rs7000921）进行检测。采用多因素logistic回归模型分析遗传变异与肿瘤淋巴结转移（tumor node metastasis, TNM）分期、远处转移的关联；应用相乘交互项和“Delta”法探讨基因-环境交互作用。结果 显性模型下，以rs4268139 CC基因型为参照，CG+GG基因型可增加病例首诊时已为晚期的风险（OR=1.64，95%CI=1.08~2.50）。rs4599828 TT基因型的病例首诊时出现远处转移的危险高于CC+CT基因型携带者（OR=2.04，95%CI=1.08~3.85）。叉生分析中，与有运动的rs4268139 CC基因型携带者相比，携带CG+GG基因型且缺乏运动的病例晚期和远处转移风险增高（OR=3.01，95%CI=1.62~5.58；OR=2.19，95%CI=1.12~4.26）。类似，rs4599828 CT+TT基因型且无运动共同增加病例晚期风险（OR=2.22，95%CI=1.34~3.68）。但未观察到有统计学意义的交互作用。结论 INST10 rs4268139 和rs4599828遗传变异可能单独以及联合缺乏运动影响HBV相关肝癌的病理特征。

Effects of INTS10 variants and gene-environment interaction on pathological characteristics of HBV associated primary liver cancer

To investigate the effect of genetic variants in INTS10 and its interaction with environmental factors on the pathological characteristics of HBV associated primary liver cancer. Methods This study enrolled 705 new cases with HBV associated primary liver cancer. Four genetic variants in the INTS10 gene，including rs4268139，rs4599828，rs7822495，and rs7000921，were genotyped. Multivariate Logistic regression model was applied to analyze the genetic association with the risks of advanced stage and distant metastasis. The multiplicative interaction term and the “Delta”method were used to evaluate the multiplicative and additive interactions，respectively. Ｒesults Under the dominant model，compared with the patients of the rs4268139 CC genotype，patients with the CG + GG genotype had a 64% increased risk of advanced cancer ( OＲ= 1. 64，95% CI = 1. 08 － 2. 50) . Carriers of the rs4599828 TT genotype had a higher risk of distant metastasis than patients with the CC + CT genotype ( OＲ = 2. 04，95% CI = 1. 08 － 3. 85) . In the crossover analysis，compared with the rs4268139 CC genotype carriers with physical exercise，the patients carrying the CG + GG genotype who lacked of exercise had an increased risk of advanced cancer and distant metastasis ( OＲ = 3. 01，95% CI = 1. 62 － 5. 58; OＲ = 2. 19，95% CI = 1. 12 － 4. 26) .Similarly，the rs4599828 CT + TT genotype and lack of exercise jointly increased the risk of advanced cancer ( OＲ = 2. 22，95% CI = 1. 34 － 3. 68) . However，no statistical interactions were observed. Conclusion The genetic variants in INST10，rs4268139 and rs4599828，may solely or jointly with lack of exercise，alter the pathological characteristics of HBV associated liver cancer.