Guo Keye, Lu Zhongming, Wang Xiaoping, Qiao Jianjun
Department of Dermatology, Shengzhou People's Hospital, Shaoxing, China.
Department of Dermatology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Transl Cancer Res. 2021 Dec;10(12):5110-5122. doi: 10.21037/tcr-21-1508.
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 gene polymorphisms and skin cancers.
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).
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 GC + GG, OR =1.03 (95% CI: 0.81-1.31); GC + CC GG, OR =1.16 (95% CI: 0.96-1.39); CC GG, OR =1.14 (95% CI: 0.86-1.53); GC GG, OR =1.16 (95% CI: 0.99-1.37); C 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 GG, OR =1.255, P=0.012; GC 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.
Current evidence showed that gene polymorphisms might not be associated with the susceptibility to skin cancer.
皮肤癌作为最常见的人体恶性肿瘤之一，是一组具有高度异质性的肿瘤，其恶性潜能、预后及治疗方法各不相同。尽管全球范围内皮肤癌的治疗取得了进展，但总体预后仍然较差。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。本荟萃分析旨在阐明基因多态性与皮肤癌之间的关系。
通过检索PubMed、Embase、Web of Science和Cochrane数据库来确定符合条件的研究。使用随机效应模型获得IL-6 174G/C和597G/A多态性与皮肤癌之间关系的合并比值比（OR）及相应的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。还进行了异质性检验、敏感性分析和发表偏倚评估。当存在发表偏倚时，使用修剪填充法调整OR。所有数据均在R（版本4.0.2）中进行分析。
本荟萃分析纳入了174G/C多态性的1705例病例和1987例对照（10篇文献），以及597G/A多态性的968例病例和998例对照（3篇文献）。在174G/C多态性的所有比较中均未发现皮肤癌风险升高：CC对GC + GG，OR = 1.03（95%CI：0.81 - 1.31）；GC + CC对GG，OR = 1.16（95%CI：0.96 - 1.39）；CC对GG，OR = 1.14（95%CI：0.86 - 1.53）；GC对GG，OR = 1.16（95%CI：0.99 - 1.37）；C对G，OR = 1.07（95%CI：0.92 - 1.24）。然后我们根据发表年份、癌症类型、样本量、NOS评分进行亚组分析。在2010年前发表年份的亚组中观察到显著差异（GC + CC对GG，OR = 1.255，P = 0.012；GC对GG，OR = 1.277，P = 0.01），而在2010年后发表年份的亚组中无统计学意义（所有比较P>0.05）。经过发表偏倚调整后，结果进一步表明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。
目前的证据表明，基因多态性可能与皮肤癌易感性无关。
