Lien Ming-Yu, Lin Chiao-Wen, Tsai Hsiao-Chi, Chen Yng-Tay, Tsai Ming-Hsui, Hua Chun-Hung, Yang Shun-Fa, Tang Chih-Hsin
Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
Oncotarget. 2017 May 9;8(19):31424-31434. doi: 10.18632/oncotarget.15615.
In Taiwan, oral cancer has causally been associated with environmental carcinogens. CCL4 (C-C chemokine ligand 4), a macrophage inflammatory protein with a key role in inflammation and immune-regulation, was implicated in carcinogenesis by facilitating instability in the tumor environment. The purpose of this study was to identify gene polymorphisms of CCL4 specific to patients with oral squamous cell carcinoma (OSCC) susceptibility and clinicopathological characteristics. A total of 2,053 participants, including 1192 healthy people and 861 patients with oral cancer, were recruited for this study. Three single-nucleotide polymorphisms (SNPs) of the CCL4 gene were analyzed by a real-time PCR. We found that the T/T homozygotes of CCL4 rs1634507 G/T polymorphism and the GG haplotype of 2 CCL4 SNPs (rs1634507 and rs10491121) combined were associated with oral-cancer susceptibility. In addition, TA haplotype significantly decreased the risks for oral cancer by 0.118 fold. Among 1420 smokers, CCL4 polymorphisms carriers with the betel-nut chewing habit had a 15.476-20.247-fold greater risk of having oral cancer compared to CCL4 wild-type (WT) carriers without the betel-nut chewing habit. Finally, patients with oral cancer who had A/G heterozygotes of CCL4 rs10491121 A/G polymorphism showed a lower risk for an advanced tumor size (> T2) (p=0.046), compared to those patients with AA homozygotes. Our results suggest that the CCL4 rs1634507 SNP have potential predictive significance in oral carcinogenesis. Gene-environment interactions of CCL4 polymorphisms might influence oral-cancer susceptibility. CCL4 rs10491121 may be a factor to predict the tumor size in OSCC patients.
在台湾，口腔癌与环境致癌物存在因果关联。CCL4（C-C趋化因子配体4）是一种在炎症和免疫调节中起关键作用的巨噬细胞炎性蛋白，它通过促进肿瘤环境的不稳定而参与致癌过程。本研究的目的是确定口腔鳞状细胞癌（OSCC）易感性及临床病理特征患者所特有的CCL4基因多态性。本研究共招募了2053名参与者，包括1192名健康人和861名口腔癌患者。通过实时PCR分析CCL4基因的三个单核苷酸多态性（SNP）。我们发现，CCL4 rs1634507 G/T多态性的T/T纯合子以及2个CCL4 SNP（rs1634507和rs10491121）组合的GG单倍型与口腔癌易感性相关。此外，TA单倍型使口腔癌风险显著降低0.118倍。在1420名吸烟者中，有嚼槟榔习惯的CCL4多态性携带者患口腔癌的风险比没有嚼槟榔习惯的CCL4野生型（WT）携带者高15.476至20.247倍。最后，与AA纯合子患者相比，CCL4 rs10491121 A/G多态性的A/G杂合子口腔癌患者出现肿瘤较大（> T2）的风险较低（p = 0.046）。我们的结果表明，CCL4 rs1634507 SNP在口腔癌发生中具有潜在的预测意义。CCL4多态性的基因-环境相互作用可能影响口腔癌易感性。CCL4 rs10491121可能是预测OSCC患者肿瘤大小的一个因素。
