ICAM-1 单核苷酸多态性与环境致癌物联合作用对口腔癌易感性及临床病理发展的影响。
Combined effects of icam-1 single-nucleotide polymorphisms and environmental carcinogens on oral cancer susceptibility and clinicopathologic development.
机构信息
Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan ; Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan.
出版信息
PLoS One. 2013 Sep 12;8(9):e72940. doi: 10.1371/journal.pone.0072940. eCollection 2013.
BACKGROUND
In Taiwan, oral cancer has causally been associated with environmental carcinogens. Intercellular adhesion molecule (ICAM)-1, a cell adhesion molecule with a key role in inflammation and immunosurveillance, was implicated in carcinogenesis by facilitating instability in the tumor environment. The current study explored the combined effect of ICAM-1 gene polymorphisms and exposure to environmental carcinogens on the susceptibility of developing oral squamous cell carcinoma (OSCC) and the clinicopathological characteristics of the tumors.
METHODOLOGY AND PRINCIPAL FINDINGS
Four single-nucleotide polymorphisms (SNPs) of the ICAM-1 gene from 595 patients with oral cancer and 561 non-cancer controls were analyzed by a real-time PCR. We found that the ICAM-1 rs5498 polymorphism and the TAGG or TACG haplotype of 4 ICAM-1 SNPs (rs3093030, rs5491, rs281432, and rs5498) combined were associated with oral-cancer susceptibility. Among 727 smokers, ICAM-1 polymorphisms carriers with the betel-nut chewing habit had a 27.49-36.23-fold greater risk of having oral cancer compared to ICAM-1 wild-type (WT) carriers without the betel-nut chewing habit. Among 549 betel-nut chewers, ICAM-1 polymorphisms carriers who smoked had a 9.93-14.27-fold greater risk of having oral cancer compared to those who carried the WT but did not smoke. Finally, patients with oral cancer who had at least 1 T allele of ICAM-1 rs5491 or 1 G allele of rs281432 were at lower risk of developing an advanced clinical stage (III/IV) (p<0.05), compared to those patients with AA or CC homozygotes.
CONCLUSIONS
Our results suggest that the ICAM-1 rs5498 SNP and either of 2 haplotypes of 4 SNPs combined have potential predictive significance in oral carcinogenesis. Gene-environment interactions of ICAM-1 polymorphisms, smoking, and betel-nut chewing might alter oral-cancer susceptibility. ICAM-1 rs5491 and rs281432 may be applied as factors to predict the clinical stage in OSCC patients.
背景
在台湾，口腔癌与环境致癌物有因果关系。细胞间黏附分子 (ICAM)-1 是一种在炎症和免疫监视中起关键作用的细胞黏附分子，它通过促进肿瘤微环境的不稳定性而参与致癌作用。本研究探讨了 ICAM-1 基因多态性与环境致癌物暴露相结合对口腔鳞状细胞癌 (OSCC) 易感性的影响，以及肿瘤的临床病理特征。
方法和主要发现
对 595 例口腔癌患者和 561 例非癌症对照者的 ICAM-1 基因的 4 个单核苷酸多态性 (SNP) 进行了实时 PCR 分析。我们发现，ICAM-1 rs5498 多态性和 4 个 ICAM-1 SNP(rs3093030、rs5491、rs281432 和 rs5498)的 TAGG 或 TACG 单倍型与口腔癌易感性相关。在 727 名吸烟者中，与未嚼槟榔的 ICAM-1 野生型 (WT) 携带者相比，嚼槟榔且携带 ICAM-1 多态性的吸烟者患口腔癌的风险增加了 27.49-36.23 倍。在 549 名嚼槟榔者中，与不吸烟的 WT 携带者相比，吸烟且携带 ICAM-1 多态性的患者患口腔癌的风险增加了 9.93-14.27 倍。最后，与 AA 或 CC 纯合子患者相比，至少携带 1 个 ICAM-1 rs5491T 等位基因或 1 个 rs281432G 等位基因的口腔癌患者发生晚期临床分期 (III/IV) 的风险较低(p<0.05)。
结论
我们的研究结果表明，ICAM-1 rs5498 SNP 以及 4 个 SNP 中 2 个单倍型的组合具有口腔癌发生的潜在预测意义。ICAM-1 多态性、吸烟和嚼槟榔的基因-环境相互作用可能改变口腔癌的易感性。ICAM-1 rs5491 和 rs281432 可作为预测 OSCC 患者临床分期的因素。
Zotero 插件