Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan ; Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan.
PLoS One. 2013 Sep 12;8(9):e72940. doi: 10.1371/journal.pone.0072940. eCollection 2013.
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.
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.
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.
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。
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)。
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。
