背景:作为最常见的身体恶性肿瘤之一,皮肤癌包含一组具有不同恶性潜能的高度异质性肿瘤,预后和治疗方法。尽管全世界在治疗皮肤癌方面取得了进展,总体预后仍然较差。最近的研究表明白细胞介素-6(IL-6)的单核苷酸多态性(SNP),包括174G/C和597G/A,可能与皮肤癌易感性有关.这项荟萃分析旨在阐明IL-6基因多态性与皮肤癌之间的关系。
方法:通过搜索PubMed,Embase,WebofScience和Cochrane使用随机效应模型获得了IL-6174G/C和597G/A多态性与皮肤癌之间关系的汇总优势比(OR)和相应的95%置信区间(CI)。对于纳入的研究,计算纽卡斯尔-渥太华量表(NOS)评分以评估研究质量.异质性测试,敏感性分析,并进行了发表偏倚评估.当存在发表偏倚时,使用修剪填充法,旨在调整OR。所有数据在R(版本4.0.2)中分析。
结果:这项荟萃分析包括174G/C多态性的1,705例和1,987例对照(10种出版物),597G/A多态性968例和998例对照(3篇出版物)。在174G/C多态性的所有比较中均未发现皮肤癌风险升高:CC与GC+GG,OR=1.03(95%CI:0.81-1.31);GC+CC与GG,OR=1.16(95%CI:0.96-1.39);CC与GG,OR=1.14(95%CI:0.86-1.53);GC与GG,OR=1.16(95%CI:0.99-1.37);Cvs.G,OR=1.07(95%CI:0.92-1.24)。然后我们根据出版年份进行了亚组分析,癌症类型,样本量,NOS得分。在2010年之前的发表年的亚组中观察到显着差异(GCCC与GG,OR=1.255,P=0.012;GC与GG,OR=1.277,P=0.01),而2010年后发表的亚组无统计学意义(所有比较P>0.05)。出版偏见调整后,结果进一步提示174G/C多态性与皮肤癌风险无关.在597G/A多态性的比较中未发现皮肤癌风险升高。
结论:目前的证据表明IL-6基因多态性可能与皮肤癌的易感性无关。
BACKGROUND: As one of the most common body malignant cancers, skin cancers contain a group of highly heterogeneous tumors with different malignant potential, prognosis and treatment methods. Despite the progress in the treatment of skin cancers worldwide, the overall prognosis is still poor. Recent studies indicated single nucleotide polymorphisms (SNPs) of interleukin-6 (IL-6), including 174G/C and 597G/A, might be associated with susceptibility to skin cancer. This meta-analysis aims to clarify the relationship between IL-6 gene polymorphisms and skin cancers.
METHODS: Eligible studies were identified from searching PubMed, Embase, Web of Science and Cochrane. Pooled odds ratio (OR) and corresponding 95% confidence interval (CI) were obtained for the relationships between IL-6 174G/C and 597G/A polymorphisms and skin cancer using random-effects models. For the included studies, the Newcastle-Ottawa scale (NOS) score was calculated to assess study quality. Heterogeneity tests, sensitivity analysis, and publication bias assessments were also performed. Trim-and-fill method was used when publication bias existed aiming to adjusting OR. All data were analyzed in R (version 4.0.2).
RESULTS: This meta-analysis included 1,705 cases and 1,987 controls for 174G/C polymorphism (10 publications), and 968 cases and 998 controls for 597G/A polymorphism (3 publications). No elevated risk of skin cancer was found in all comparisons for 174G/C polymorphism: CC vs. GC + GG, OR =1.03 (95% CI: 0.81-1.31); GC + CC vs. GG, OR =1.16 (95% CI: 0.96-1.39); CC vs. GG, OR =1.14 (95% CI: 0.86-1.53); GC vs. GG, OR =1.16 (95% CI: 0.99-1.37); C vs. G, OR =1.07 (95% CI: 0.92-1.24). Then we performed subgroup analysis based on publication year, the cancer type, sample size, NOS score. Significant differences were observed in the subgroup of publication year before 2010 (GC + CC vs. GG, OR =1.255, P=0.012; GC vs. GG, OR =1.277, P=0.01), while there is no statistical significance in the subgroup of publication year after 2010 (P>0.05 for all comparisons). After publication bias adjustment, the results further suggested that 174G/C polymorphism is not associated with the risk of skin cancer. No elevated risk of skin cancer was found in the comparisons for 597G/A polymorphism.
CONCLUSIONS: Current evidence showed that IL-6 gene polymorphisms might not be associated with the susceptibility to skin cancer.