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RAD51 和 XRCC3 单核苷酸多态性在口腔和口咽癌中的临床病理意义。

Clinicopathological significance of SNPs in RAD51 and XRCC3 in oral and oropharyngeal carcinomas.

机构信息

Department of Dentistry, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.

Department of Dentistry, Federal University of Sergipe, Lagarto, Sergipe, Brazil.

出版信息

Oral Dis. 2019 Jan;25(1):54-63. doi: 10.1111/odi.12943. Epub 2018 Aug 17.

Abstract

BACKGROUND

This study investigated the influence of single nucleotide polymorphisms (SNP) in RAD51 and XRCC3 on susceptibility to oral and oropharyngeal squamous cell carcinomas (SCC) and determined their clinicopathological significance.

SUBJECTS AND METHODS

SNPs rs1801320 and rs1801321 in RAD51 and rs861539 in XRCC3 were genotyped in 81 patients presenting oral SCC, 45 presenting oropharyngeal SCC, and 130 healthy controls, using TaqMan allelic discrimination assays. Multiple logistic regression models were used to explore the association between SNPs and cancer development, as well as gene-gene (GxG) interaction and gene-environmental factor (GxE) interaction. Clinicopathological associations were verified through the chi-square test, and univariate and multivariate methods were applied for survival analyses.

RESULTS

Although allelic and genotypic models and the GxG interaction analysis were nonsignificant, the GxE analysis revealed synergistic effects of the risk alleles of rs1801320, rs1801321, and rs861539 with smoking and alcohol consumption on susceptibility to oral and oropharyngeal SCC. Furthermore, oropharyngeal SCC patients carrying the XRCC3 rs861539 GT/TT genotype (T risk allele) presented a shorter overall survival than GG genotype carriers.

CONCLUSION

Combined effects of RAD51 (rs1801320 and rs1801321) and XRCC3 (rs861539) SNPs with environmental carcinogens (tobacco and alcohol) are associated with oral and oropharyngeal SCC development.

摘要

背景

本研究旨在探讨 RAD51 和 XRCC3 单核苷酸多态性(SNP)对口腔和口咽鳞状细胞癌(SCC)易感性的影响,并确定其临床病理意义。

方法

采用 TaqMan 等位基因鉴别分析,对 81 例口腔 SCC 患者、45 例口咽 SCC 患者和 130 例健康对照者的 RAD51 基因 rs1801320 和 rs1801321 位点、XRCC3 基因 rs861539 位点 SNP 进行基因分型。采用多因素逻辑回归模型探讨 SNP 与癌症发生的相关性,以及基因-基因(GxG)交互作用和基因-环境因素(GxE)交互作用。采用卡方检验验证临床病理相关性,采用单因素和多因素方法进行生存分析。

结果

尽管等位基因和基因型模型以及 GxG 交互作用分析无统计学意义,但 GxE 分析显示 rs1801320、rs1801321 和 rs861539 风险等位基因与吸烟和饮酒的协同作用与口腔和口咽 SCC 的易感性相关。此外,携带 XRCC3 rs861539 GT/TT 基因型(T 风险等位基因)的口咽 SCC 患者的总生存时间短于 GG 基因型携带者。

结论

RAD51(rs1801320 和 rs1801321)和 XRCC3(rs861539)SNP 与环境致癌物(烟草和酒精)的联合作用与口腔和口咽 SCC 的发生有关。

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