ABCB1基因多态性与接受紫杉烷治疗的食管鳞状细胞癌患者预后的相关性
Association between polymorphisms of ABCB1 and prognosis in esophageal squamous cell carcinoma patients treated with taxane.
作者信息
Sun Zhiwei, Yang Xin, Du Feng, Shi Youwu, Sun Jing, Jia Jun, Liu Chuanling, Xiao Yanjie, Yu Jing, Zhang Xiaodong, Yang Ying
机构信息
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, China), The VIP-II Gastrointestinal Cancer Division of Medical Department, Peking University Cancer Hospital & Institute, Beijing, China.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, China), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, China.
出版信息
J Gene Med. 2022 Jul;24(7):e3434. doi: 10.1002/jgm.3434. Epub 2022 Jun 16.
BACKGROUND
In China, most esophageal cancer patients are squamous cell carcinomas and are treated with taxane-containing regimens; however, few studies have examined taxane pharmacokinetics genes and esophageal squamous cell carcinoma (ESCC) prognosis.
METHODS
In total, 227 pathologically confirmed ESCC patients receiving chemotherapy with taxane were included in the analysis. We genotyped seven SNPs (rs1045642, rs2032582 and rs3213619 of ABCB1; rs2231137 and rs2231142 of ABCG2; and ABCC1 rs246221 and ABCC2 rs3740066) and analyzed their relationship with overall survival.
RESULTS
With a retrospective cohort study design, by Cox regression and semi-Bayesian shrinkage, in the genetic recessive model, the variant homozygote of ABCB1 rs1045642 was inversely associated with survival (semi-Bayesian shrinkage crude hazard ratio = 1.82, 95% confidence interval = 1.00, 3.31; p = 0.0482).
CONCLUSIONS
Because of inherent defects of the research itself, the finding that the ABCB1 rs1045642 variant was related to poor prognosis in ESCC patients treated with taxane-containing regimens needs to be tested in a larger population and by using more genetic and molecular mechanism experiments.
背景
在中国，大多数食管癌患者为鳞状细胞癌，接受含紫杉烷的治疗方案；然而，很少有研究探讨紫杉烷药代动力学基因与食管鳞状细胞癌（ESCC）预后的关系。
方法
总共纳入227例经病理确诊且接受紫杉烷化疗的ESCC患者进行分析。我们对7个单核苷酸多态性（ABCB1的rs1045642、rs2032582和rs3213619；ABCG2的rs2231137和rs2231142；以及ABCC1的rs246221和ABCC2的rs3740066）进行基因分型，并分析它们与总生存期的关系。
结果
采用回顾性队列研究设计，通过Cox回归和半贝叶斯收缩法，在遗传隐性模型中，ABCB1 rs1045642的变异纯合子与生存期呈负相关（半贝叶斯收缩法粗风险比=1.82，95%置信区间=1.00，3.31；p=0.0482）。
结论
由于本研究本身存在固有缺陷，ABCB1 rs1045642变异与接受含紫杉烷方案治疗的ESCC患者预后不良的这一发现，需要在更大规模人群中进行验证，并通过更多的基因和分子机制实验加以检验。
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