Abstract
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.
Highlights
Oral cancer is one of the common malignant cancer in the head and neck region, more than 90% are squamous cell carcinomas (OSCCs) [1]
We found that the T/T homozygotes of CCL4 rs1634507 G/T polymorphism and the GG haplotype of 2 CCL4 single-nucleotide polymorphisms (SNPs) combined were associated with oral-cancer susceptibility
Our results suggest that the CCL4 rs1634507 SNP have potential predictive significance in oral carcinogenesis
Summary
Oral cancer is one of the common malignant cancer in the head and neck region, more than 90% are squamous cell carcinomas (OSCCs) [1]. The development of OSCC is mediated by accumulation of multiple genetic alterations and by environmental carcinogen-exposure influences. Singlenucleotide polymorphisms (SNPs), the most common type of DNA sequence variation influenced gene expression, protein function and disease susceptibility in particular individuals. SNP had potential predictive significance risk of oral cancer in previous studies [7,8,9]. The relationship between genetic polymorphisms and the environmental carcinogens was reported [10, 11], identifying principal genes related to the susceptibility for OSCC is important for disease early detection
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