CLOCK基因多态性与子宫内膜异位症相关性卵巢癌患者化疗敏感性的关系  

The relationship between CLOCK gene polymorphism and chemotherapy sensitivity in patients with endometriosis-related ovarian cancer

作　　者：崔建涛 陈娜[1] 高娜[1] 张玉丽 陈秀英[1] 李晓丹 卞欣 张士表[1] CUI Jiantao;CHEN Na;GAO Na;ZHANG Yuli;CHEN Xiuying;LI Xiaodan;BIAN Xin;ZHANG Shibiao(Department of Gynecology,Cangzhou Hospital of Integrated TCM-WM-Hebei,Cangzhou,Hebei 061000,China)

机构地区：[1]河北省沧州中西医结合医院妇一科,河北沧州061000

出　　处：《中国优生与遗传杂志》2022年第4期625-631,共7页Chinese Journal of Birth Health & Heredity

基　　金：河北省中医药管理局科研计划项目(2020486)。

摘　　要：目的 探讨CLOCK基因单核苷酸多态性(SNP)与子宫内膜异位症相关性卵巢癌(EAOC)患者化疗敏感性的关系。方法 选择2014年3月至2015年9月在我院接受治疗的EAOC患者129例,年龄38~67岁,平均年龄(46.32±8.96)岁。对患者进行铂类药物为基础的联合化疗,根据患者化疗敏感情况将129例患者分为敏感组(n=71)和不敏感组(n=58),对比两组患者的一般资料和病理特征,采用PCR检测CLOCK基因SNP位点的基因分型及分布情况,探讨不同基因型与化疗效果的相关性,采用Hardy-Weinberg遗传平衡吻合度检验法计算各基因型的理论值。通过Logistic回归分析EAOC患者化疗敏感性的危险因素,分析不同病理特征及基因型对EAOC患者预后影响。结果 rs3749474位点等位基因C/T,分型CC、TT、CT;rs3817444位点等位基因C/A,分型为CC、AA、CA;rs12504300位点等位基因C/G,分型为CC、GG、CG;rs3805148位点等位基因C/A,分型为CC、AA、CA。与敏感组患者相比,不敏感组患者的FIGO分期多为晚期,分化程度主要为未分化-低分化,残瘤径≥1 cm和腹腔转移的人数比例高于敏感组,差异具有统计学意义(P<0.05),4个CLOCK基因SNP位点在两组间的分布频率差异也具有统计学意义(P<0.05)。多因素Logistic回归分析显示,影响患者化疗敏感性的因素中,FIGO晚期、低未分化、残瘤径≥1 cm、腹腔转移、CLOCK rs3749474携带T基因型、CLOCK rs3817444携带A基因型、CLOCK rs12504300携带G基因型、CLOCK rs3805148携带C基因型,是影响EAOC患者化疗敏感性的独立危险因素。Kaplan-Meier结果显示FIGO分期、分化程度、残瘤径和腹腔转移对PFS和OS有影响;rs3749474、rs38174448、rs12504300、rs3805148位点均只对OS有影响,对PFS无影响。结论 CLOCK基因的rs3749474位点、rs3817444位点、rs12504300位点和rs3805148位点可能成为预测EAOC患者化疗敏感性及预后的重要标志物。Objective To explore the relationship between CLOCK gene single nucleotide polymorphism(SNP) and chemotherapy sensitivity of patients with endometriosis-related ovarian cancer(EAOC). Methods We selected 129 EAOC patients who were treated in our hospital from March 2014 to September 2015, aged from 38 to 67 years, with an average age of(46.32±8.96) years. The patients were treated with platinum-based drug-based combination chemotherapy, and 129 patients were divided into sensitive group(n=71) and insensitive group(n=58) according to their sensitivity to chemotherapy, and the general data of the two groups were compared. And pathological characteristics, PCR was used to detect the genotyping and distribution of SNP sites in the CLOCK gene, to explore the correlation between different genotypes and chemotherapy effects,and to calculate the theoretical value of each genotype using the Hardy-Weinberg genetic balance and fit test method. Logistic regression was used to analyze the risk factors of chemotherapy sensitivity in EAOC patients, and the influence of different pathological characteristics and genotypes on the prognosis of EAOC patients was analyzed. Results rs3749474 locus allele C/T, type CC, TT, CT;rs3817444 locus allele C/A, type CC, AA, CA;rs12504300 locus allele C/G, type: CC, GG, CG;rs3805148 locus allele C/A, the types are CC, AA, CA. Compared with patients in the sensitive group, the FIGO staging of patients in the insensitive group is mostly advanced, and the degree of differentiation is mainly undifferentiated-poorly differentiated. The proportion of residual tumors ≥1 cm in diameter and abdominal metastasis is higher than that in the sensitive group, and the difference is statistically significant(P<0.05), the distribution frequency difference of the 4 CLOCK gene SNP loci between the two groups was also statistically significant(P<0.05). Multivariate logistic regression analysis showed that among the factors that affect the chemotherapy sensitivity of patients, FIGO is advanced, poorly undifferen

关 键 词：CLOCK基因 基因多态性 子宫内膜异位症相关卵巢癌 化疗敏感性 

分 类 号：R711.71[医药卫生—妇产科学] R737.31[医药卫生—临床医学]