Yang Changsen, Song Tiangang, Mo Yajie, Wu Peixuan, Tian Haokun, Wen Lequan, Gao Yun
Joint Program of Nanchang University and Queen Mary University of London, Nanchang University, Nanchang, China.
The Second Affiliated Hospital of Nanchang University, Nanchang University, Nanchang, China.
Front Oncol. 2023 Aug 1;13:1133055. doi: 10.3389/fonc.2023.1133055. eCollection 2023.
Although numerous case-control studies have explored the association between CC cytokine ligand-4 (CCL4) expression and cancer susceptibility, their results have been conflicting. This study aimed to determine the still-unknown connection of CCL4 rs10491121 and rs163450 polymorphisms with cancer susceptibility.
Several databases, such as Web of Science, PubMed, and EMBASE, were searched for papers published since the creation of the database until November 2, 2022. Using RevMan 5.4 and StataMP 17 softwares, meta-analysis and subgroup analysis were performed after article screening and data extraction. For sensitivity analyses, one-by-one exclusion method was used, and then, the comprehensive effect was estimated and compared with that before exclusion. Trial sequential analysis (TSA)was performed using TSA 0.9.5.10 beta software.
Seven case-control studies encompassing 3559 cases and 4231 controls were included. The value was greater than 0.05 for all models, indicating the absence of an evident relationship of CCL4 gene rs10491121 and rs1634507 polymorphisms with cancer susceptibility. However, in the subgroup analysis of rs10491121, the values in all models studied by us except GA AA were <0.05 considering the Chinese subgroup, suggesting that the G allele is a risk factor for cancer in the Chinese population. Besides, in the subgroup analysis of rs1634507 considering oral cancer, the co-dominant model GG TT, dominant model GG + GT TT, and allele model G T groups showed OR < 1 and < 0.05, indicating that the G allele was a protective factor of oral cancer. However, for other cancer types, all the models studied by us except GG GT showed OR > 1 and < 0.05, indicating that the G allele was a risk factor for these other cancers. Despite the statistically significant results, sensitivity analysis had some stability limitations, and TSA results suggested the possibility of false positives.
For rs10491121, we identified an association between the G allele and increased cancer risk in the Chinese population. For rs1634507, the G allele was not found to be associated with reduced risk of oral cancer and increased risk of other cancers studied by us.
尽管众多病例对照研究探讨了CC细胞因子配体4（CCL4）表达与癌症易感性之间的关联，但其结果相互矛盾。本研究旨在确定CCL4基因rs10491121和rs163450多态性与癌症易感性之间尚不清楚的联系。
检索了Web of Science、PubMed和EMBASE等多个数据库，查找自数据库创建至2022年November 2日发表的论文。在进行文献筛选和数据提取后，使用RevMan 5.4和StataMP 17软件进行荟萃分析和亚组分析。敏感性分析采用逐一排除法，然后估计综合效应并与排除前进行比较。使用TSA 0.9.5.10 beta软件进行试验序贯分析（TSA）。
纳入了7项病例对照研究，共3559例病例和4231例对照。所有模型的P值均大于0.05，表明CCL4基因rs10491121和rs1634507多态性与癌症易感性之间不存在明显关联。然而，在rs10491121的亚组分析中，考虑中国亚组时，除GA对AA外，我们研究的所有模型中的P值均<0.05，表明G等位基因是中国人群患癌的危险因素。此外，在考虑口腔癌的rs1634507亚组分析中，共显性模型GG对TT、显性模型GG + GT对TT以及等位基因模型G对T组的OR<1且P<0.05，表明G等位基因是口腔癌的保护因素。然而，对于其他癌症类型，除GG对GT外，我们研究的所有模型的OR>1且P<0.05，表示G等位基因是这些其他癌症的危险因素。尽管结果具有统计学意义，但敏感性分析存在一些稳定性限制，TSA结果提示存在假阳性的可能性。
对于rs10491121，我们发现中国人群中G等位基因与癌症风险增加之间存在关联。对于rs1634507，未发现G等位基因与口腔癌风险降低以及我们研究的其他癌症风险增加有关。
