title: RAGE gene polymorphism and environmental factor in the risk of oral cancer.
abstract: Oral squamous cell carcinoma is a common neoplasm that is known to be causally associated with genetic factors and environmental carcinogens. The receptor for advanced glycosylation endproducts (RAGE) is a transmembrane protein of the immunoglobulin superfamily with broad specificity for multiple ligands, and it has been shown to play vital roles in several pathophysiologic processes, including diabetes, Alzheimer disease, renal disease, cardiovascular disease, and cancer. The present study aimed to assess the influences of RAGE gene polymorphisms, combined with environmental carcinogens on the predisposition to oral tumorigenesis. Five polymorphisms of the RAGE gene-including -374T>A (rs1800624), -429T>C (rs1800625), 1704G>T (rs184003), Gly82Ser (rs2070600), and a 63-bp deletion allele (-407 to -345)-were examined from 592 controls and 618 patients with oral cancer. We found that individuals carrying the polymorphic allele of rs1800625 are more susceptible to oral cancer (odds ratio [OR], 1.899; 95% confidence interval [CI], 1.355 to 2.661; adjusted OR [AOR], 2.053; 95% CI, 1.269 to 3.345) after adjustment for age, sex, betel nut chewing, and tobacco consumption. Moreover, we observed a significant association of rs1800625 variants with late-stage tumors (stage III/IV, OR, 1.736; 95% CI, 1.126 to 2.677; AOR, 1.771; 95% CI, 1.101 to 2.851) and large-size tumors (>2 cm in the greatest dimension; OR, 1.644; 95% CI, 1.083 to 2.493; AOR, 1.728; 95% CI, 1.089 to 2.741). Based on behavioral exposure of environmental carcinogens, the presence of 4 RAGE single-nucleotide polymorphisms (SNPs), combined with betel quid chewing and/or tobacco use, greatly augmented the risk of oral cancer. In addition, carriers of particular haplotypes of the 4 RAGE SNPs examined are more prone to develop oral cancer. These results indicate an involvement of RAGE SNP rs1800625 in the development of oral squamous cell carcinoma and implicate the interaction between RAGE gene polymorphisms and environmental mutagens as a predisposing factor of oral carcinogenesis.
authors.affiliation: Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospitals, Linkou, Taiwan.
authors.forename: S
authors.initials: S
authors.lastname: Su
authors.affiliation: Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: M
authors.initials: M
authors.lastname: Chien
authors.affiliation: Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: C
authors.initials: C
authors.lastname: Lin
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Changhua Christian Hospital, Changhua, Taiwan Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: M
authors.initials: M
authors.lastname: Chen
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan ysf@csmu.edu.tw.
authors.forename: S
authors.initials: S
authors.lastname: Yang
mesh_terms: D000225:Adenine; D001114:Areca / Q000009:adverse effects; D020029:Base Pairing / Q000235:genetics; D001483:Base Sequence / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics; D016022:Case-Control Studies; D003596:Cytosine; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D017127:Glycation End Products, Advanced / Q000235:genetics*; D005998:Glycine / Q000235:genetics; D006147:Guanine; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics*; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics*; D012307:Risk Factors; D017384:Sequence Deletion / Q000235:genetics; D012694:Serine / Q000235:genetics; D013941:Thymine; D064424:Tobacco Use / Q000009:adverse effects
chemical_list: D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D012694:Serine; D006147:Guanine; D003596:Cytosine; D000225:Adenine; D013941:Thymine; D005998:Glycine
keywords: betel quid; haplotype; oral squamous cell carcinoma; receptor for advanced glycosylation endproducts; single-nucleotide polymorphisms; tobacco