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Impact of Polymorphisms in Casein Kinase 1 Epsilon and Environmental Factors in Oral Cancer Susceptibility.

ABSTRACT: In Taiwan, the incidence rate of oral cancer is constantly increasing. Polymorphisms and lifestyle habits are major contributing factors to the development of oral cancer in such cases. Casein kinase 1 epsilon (CK1?) gene expression plays a role in numerous cancers, and the knockdown of CK1? induces tumor cell-selective cytotoxicity. The present study was designed to determine the effects of CK1? gene polymorphisms combined with environmental carcinogens on susceptibility to developing oral squamous cell carcinoma and its clinicopathological status. Four single-nucleotide polymorphisms (SNPs) in CK1? gene (rs135745, rs135764, rs1997644 and rs2075984) from 741 oral cancer patients and 462 healthy controls were analyzed using real-time polymerase chain reaction. Our results shown that variant types (GC) of CK1? polymorphic rs135745 exhibited a significantly higher risk of 1.41 (95% confidence interval [CI]: 1.036-1.919) for oral cancer than did wild type alleles. Furthermore, these CK1? gene SNPs along with betel-quid chewing and/or tobacco use further increased susceptibility to oral cancer. Moreover, variant genotypes (GC+CC) of CK1? rs135745 were significantly associated with lymph node metastasis. These results suggested that the CK1? gene polymorphism is associated with the clinicopathological development of oral cancer and increases individuals' susceptibility to environmental carcinogens (e.g., smoking and betel-quid chewing) in terms of developing oral cancer.

SUBMITTER: Lin SH

PROVIDER: S-EPMC6775616 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Impact of Polymorphisms in Casein Kinase 1 Epsilon and Environmental Factors in Oral Cancer Susceptibility.

Lin Shu-Hui SH Chen Mu-Kuan MK Chang Julia Hueimei JH Velmurugan Bharath Kumar BK Annamanedi Madhavi M Su Shih-Chi SC Yeh Kun-Tu KT Yang Shun-Fa SF

Journal of Cancer 20190828 21

In Taiwan, the incidence rate of oral cancer is constantly increasing. Polymorphisms and lifestyle habits are major contributing factors to the development of oral cancer in such cases. Casein kinase 1 epsilon (CK1ε) gene expression plays a role in numerous cancers, and the knockdown of CK1ε induces tumor cell-selective cytotoxicity. The present study was designed to determine the effects of CK1ε gene polymorphisms combined with environmental carcinogens on susceptibility to ...[more]

PMID: 31602258

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Project description: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.

Dataset Information

Impact of Polymorphisms in Casein Kinase 1 Epsilon and Environmental Factors in Oral Cancer Susceptibility.

Publications

Impact of Polymorphisms in Casein Kinase 1 Epsilon and Environmental Factors in Oral Cancer Susceptibility.

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