CD44 Gene Polymorphisms and Environmental Factors on Oral Cancer Susceptibility in Taiwan

Abstract

BackgroundOral squamous cell carcinoma (OSCC) is the fourth leading cause of male cancer death in Taiwan. Exposure to environmental carcinogens is the primary risk factor for developing OSCC. CD44, a well-known tumor marker, plays a crucial role in tumor cell differentiation, invasion, and metastasis. This study investigated CD44 single-nucleotide polymorphisms (SNPs) with environmental risk factors to determine OSCC susceptibility and clinicopathological characteristics.Methodology/Principal FindingsReal-time polymerase chain reaction (PCR) was used to analyze 6 SNPs of CD44 in 599 patients with oral cancer and 561 cancer-free controls. We determined that the CD44 rs187115 polymorphism carriers with the genotype AG, GG, or AG+GG were associated with oral cancer susceptibility. Among 731 smokers, CD44 polymorphisms carriers with the betel-nut chewing habit had a 10.30–37.63-fold greater risk of having oral cancer compared to CD44 wild-type (WT) carriers without the betel-nut chewing habit. Among 552 betel-nut chewers, CD44 polymorphisms carriers who smoked had a 4.23–16.11-fold greater risk of having oral cancer compared to those who carried the WT but did not smoke. Finally, we also observed that the stage III and IV oral cancer patients had higher frequencies of CD44 rs187115 polymorphisms with the variant genotype (AG+GG) compared with the wild-type (WT) carriers.ConclusionOur results suggest that gene–environment interactions between the CD44 polymorphisms and betel quid chewing and tobacco smoking increase the susceptibility to oral cancer development. Patients with CD44 rs187115 variant genotypes (AG+GG) were correlated with a higher risk of oral cancer development, and these patients may possess greater chemoresistance to advanced- to late-stage oral cancer than WT carriers do. The CD44 rs187115 polymorphism has potential predictive significance in oral carcinogenesis and also may be applied as factors to predict the clinical stage in OSCC patients.

Cluster of Differentiation 44 (CD44) Gene Variants: A Putative Cancer Stem Cell Marker in Risk Prediction of Bladder Cancer in North Indian Population

“…Winder et al [15] found CD44rs 187116 to be significantly associated with tumor recurrence in gastric adenocarcinoma, Zhou et al [20] found CD44 rs187116 to be involved in breast cancer progression. The CD44 rs187115 polymorphism has potential predictive significance in oral carcinogenesis in Taiwanian population [29].…”

Micro-ribonucleic acid 143 (MiR-143) inhibits oral squamous cell carcinoma (OSCC) cell migration and invasion by downregulation of phospho-c-Met through targeting CD44 v3

“…14 Moreover, both CD44 v3 and c-Met are upregulated in OSCC. [15][16][17][18] Our previous studies have shown that the overexpression of miR-143 is closely related to invasion and migration ability in the OSCC cell lines. To investigate whether c-Met was associated with the role of miR-143emediated inhibition of invasion and migration in OSCC cells, the expression level of phosphorylation c-Met was identified by using Western blot.…”

Pinostilbene Hydrate Suppresses Human Oral Cancer Cell Metastasis by Downregulation of Matrix Metalloproteinase-2 Through the Mitogen-Activated Protein Kinase Signaling Pathway

“…Oral squamous cell carcinoma (OSCC), the most common primary malignancy occurring in the head and neck, has approximately 500, 000 new cases reported each year [1] and is the fourth most common male cancer and the fourth leading cause of male cancer death in Taiwan [2]. The use of tobacco and alcohol has been associated with oral cancer [3,4].…”