Department of Gynecology and Oncology, Guangxi Medical University Cancer Hospital and Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Ministry of Education, Nanning, China.
Medicine (Baltimore). 2021 Dec 17;100(50):e28030. doi: 10.1097/MD.0000000000028030.
Gynecological malignant tumor is a serious threat to women's health, cervical cancer, endometrial cancer and ovarian cancer are the most common. The eponymous protein encoded by the XRCC1 (X-ray repair cross complementation 1) gene is an important functional protein in the process of single-stranded DNA damage. Non-synonymous mutations of XRCC1 gene cause amino acid sequence changes that affect protein function and DNA repair ability, and may affect the interaction with other DNA repair proteins, leading to increased risk of tumor development. Many studies have assessed the association between XRCC1 gene polymorphism and the risk of cancer in the female reproductive system, but the results have been inconclusive. In this study, the relationship between XRCC1 Arg399Gln, Arg194Trp, Arg280His single nucleotide polymorphisms and susceptibility to gynecological malignancies was further explored by meta-analysis.
English database: Pubmed, Medline, Excerpta Medica Database, Cochrance, etc; Chinese database: China national knowledge infrastructure, Wanfang Database, etc. STATA14 was used for statistical analysis, such as odd ratio (OR) value, subgroup analysis, heterogeneity test, sensitivity analysis, and publication bias.
In gynecologic cancers, the allele frequency difference of Arg399Gln case control group was statistically significant (GvsA: P = .007). There was no significant difference in allele frequency in the Arg194Trp and Arg280His case control groups (P = .065, 0.198). In different gene models, Arg399Gln was significantly correlated with gynecologic cancers susceptibility (GGvs AA: OR 0.91; 95% confidence interval [CI], 0.85 0.98); Arg194Trp was significantly correlated with gynecologic cancers susceptibility (CCvs TT: OR 0.94; 95% CI 0.88,1.00; CCvs CT: OR 0.97; 95% CI 0.90, 1.05); Arg280His was significantly correlated with gynecologic cancers susceptibility (GGvs AA: OR 0.98; 95% CI 0.94, 1.02; GGvs GA: OR 1.00;95% CI 0.97, 1.04). In the subgroup analysis, Arg399Gln and Arg194Trp were significantly correlated with gynecologic cancers susceptibility in the Asian race (P = .000, 0.049). In the analysis of different cancer subgroups, Arg399Gln and cervical cancer susceptibility were statistically significant (P = .039). Arg194Trp and endometrial cancer susceptibility were statistically significant (P = .033, 0.001).
XRCC1 Arg399Gln, Arg194Trp, Arg280His single nucleotide polymorphisms were associated with gynecologic cancer susceptibility. Arg399Gln genotype was statistically significant in relation to cervical cancer susceptibility. Arg194Trp genotype was statistically significant in relation to endometrial cancer susceptibility.
妇科恶性肿瘤是严重威胁妇女健康的疾病,宫颈癌、子宫内膜癌和卵巢癌最为常见。XRCC1(X 射线修复交叉互补基因 1)基因编码的同义蛋白是单链 DNA 损伤过程中的重要功能蛋白。XRCC1 基因的非同义突变导致氨基酸序列改变,影响蛋白功能和 DNA 修复能力,可能影响与其他 DNA 修复蛋白的相互作用,从而增加肿瘤发生的风险。许多研究评估了 XRCC1 基因多态性与女性生殖系统癌症风险之间的关系,但结果尚无定论。本研究通过荟萃分析进一步探讨了 XRCC1 Arg399Gln、Arg194Trp、Arg280His 单核苷酸多态性与妇科恶性肿瘤易感性的关系。
英文数据库:Pubmed、Medline、Excerpta Medica Database、Cochrance 等;中文数据库:中国知网、万方数据库等。采用 STATA14 进行统计分析,如比值比(OR)值、亚组分析、异质性检验、敏感性分析和发表偏倚。
在妇科癌症中,Arg399Gln 病例对照组的等位基因频率差异有统计学意义(GvsA:P=0.007)。Arg194Trp 和 Arg280His 病例对照组的等位基因频率无显著性差异(P=0.065,0.198)。在不同的基因模型中,Arg399Gln 与妇科癌症易感性显著相关(GGvsAA:OR0.91;95%置信区间[CI],0.85~0.98);Arg194Trp 与妇科癌症易感性显著相关(CCvsTT:OR0.94;95%CI0.88,1.00;CCvsCT:OR0.97;95%CI0.90,1.05);Arg280His 与妇科癌症易感性显著相关(GGvsAA:OR0.98;95%CI0.94,1.02;GGvsGA:OR1.00;95%CI0.97,1.04)。亚组分析显示,Arg399Gln 和 Arg194Trp 与妇科癌症易感性在亚洲人群中具有显著相关性(P=0.000,0.049)。在不同癌症亚组的分析中,Arg399Gln 与宫颈癌易感性具有统计学意义(P=0.039)。Arg194Trp 与子宫内膜癌易感性具有统计学意义(P=0.033,0.001)。
XRCC1 Arg399Gln、Arg194Trp、Arg280His 单核苷酸多态性与妇科癌症易感性相关。Arg399Gln 基因型与宫颈癌易感性显著相关。Arg194Trp 基因型与子宫内膜癌易感性显著相关。