Association of SDF-1 and CXCR4 Polymorphisms With Susceptibility to Oral and Pharyngeal Squamous Cell Carcinoma

• Published in: Anticancer research Vol. 39; no. 6; pp. 2891 - 2902
• Main Authors: Huang, Sin-Jhih, Tseng, Yu-Kai, Lo, Yi-Hao, Wu, Pi-Chuang, Lee, Jang-Hwa, Liou, Huei-Han, Liang, Chi-Chuang, Yang, Cheng-Mei, Wang, Cheng-Ching, Yen, Liang-Ming, Lin, Yun-Chung, Lin, Min-Hsi, Ger, Luo-Ping, Tsai, Kuo-Wang
• Format: Journal Article
• Language: English
• Published: Greece International Institute of Anticancer Research 01.06.2019
• Subjects: Alcohol; Alcohols; Cancer; Carcinoma, Squamous Cell - genetics; Chemokine CXCL12 - genetics; Chemokines; Chewing; Confidence intervals; CXC chemokines; CXCR4 protein; Disease Progression; Ethanol - adverse effects; Female; Genetic Association Studies; Genetic diversity; Genetic markers; Genetic Predisposition to Disease; Genetic variance; Genotype; Genotypes; Habits; Humans; Male; Middle Aged; Mouth Neoplasms - chemically induced; Mouth Neoplasms - genetics; Pharyngeal Neoplasms - chemically induced; Pharyngeal Neoplasms - genetics; Pharynx; Polymerase chain reaction; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Receptors, CXCR4 - genetics; Risk analysis; Risk factors; SDF-1 protein; Smoking; Squamous cell carcinoma; Synergistic effect; Taiwan; Throat cancer; Tobacco; Tobacco smoking; Tobacco, Smokeless - adverse effects; Taiwan; SDF-1; CXCR4; SNP; oral cancer
• ISSN: 0250-7005; 1791-7530
• DOI: 10.21873/anticanres.13418

Long-term exposure to betel quid (BQ)-, cigarette-, and alcohol-induced chronic inflammation is a crucial risk factor for oral and pharyngeal squamous cell carcinoma (OPSCC) progression. We analyzed the genotypes of stromal-cell-derived factor-1 (SDF-1) and CXC-chemokine receptor-4 (CXCR4) and determined the association between their polymorphisms and the risk of OPSCC. This study consisted of 452 patients with pathologically proved OPSCC and 424 sex- and age-matched cancer-free controls. The genotypes of SDF-1 and CXCR4 were detected through the TaqMan real-time polymerase chain reaction (PCR) method. Our data indicated that the C allele and C/C genotypes of CXCR4 were significantly associated with OPSCC [adjusted odds ratio (AOR)=1.41, 95% confidence interval (CI):1.02-1.96, p=0.037 and AOR=1.51, 95% CI:1.05-2.17, p=0.028, respectively] and OSCC (AOR=1.41, 95%CI:1.00-2.00, p=0.049 and AOR=1.49, 95%CI:1.01-2.20, p=0.044, respectively) risk. Patients with genetic polymorphisms of the genotype combination SDF-1/CXCR4 had a higher risk of OSCC (p trend=0.033). We analyzed the effects of CXCR4 genetic variants on susceptibility to OPSCC in patients with different risk habits of BQ chewing, tobacco smoking and alcohol consumption, and revealed that C/T+T/T genotypes exerted an increased risk only in patients with one (AOR=2.68, p=0.036) or two risk habits (AOR=2.02, p=0.027) compared to patients with the C/C genotype. We concluded that CXCR4 C>T can be used as a genetic marker of susceptibility to OPSCC, particularly in OPSCC patients with one or two types of risk habits with a synergistic effect.