RAGE Gene Polymorphism and Environmental Factor in the Risk of Oral Cancer
Open accessAbstract
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.
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In cigarette smokers, elevated levels of RAGE are positively correlated with the development of oral squamous cell, lung, and breast carcinoma.
“Furthermore, in cigarette smokers, elevated levels of RAGE are positively correlated with the development of oral squamous cell, lung, and breast carcinoma93,94.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [94]
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- Authors
- Su, S., Chien, M., Lin, C., Chen, M., & Yang, S.
- Affiliations
- Chang Gung Memorial Hospital (TW)
- Wan Fang Hospital (TW)
- Chung Shan Medical University Hospital (TW)
- Changhua Christian Hospital (TW)
- Venue
- Journal of Dental Research
- Publisher
- SAGE Publications
- Published
- 2015-01-12
- Volume
- 94
- Issue
- 3
- Pages
- 403-411
- ISSN
- 0022-0345 (ISSN-L)
- 1544-0591
- PMC
- PMC4814014
- OpenAlex
- W1982063000
- Cited by
- 49
- References
- 42
- Citations by year
- 2026: 2 · 2024: 3 · 2023: 1 · 2022: 4 · 2021: 8 · 2020: 1 · 2019: 8 · 2018: 6 · 2017: 6 · 2016: 7 · 2015: 3
- FWCI
- 6.06
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Dental Research (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Health Sciences › Dentistry › Periodontics › Oral Health Pathology and Treatment
- Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
- Keywords
- RAGE gene polymorphisms, oral squamous cell carcinoma, oral cancer risk, betel quid chewing, tobacco use, environmental carcinogens, tumor stage, tumor size, genetic susceptibility
- MeSH terms
- Receptor for Advanced Glycation End Products, Adenine, Areca, Base Sequence, Cytosine, Female, Gene Frequency, Glycine, Guanine, Haplotypes, Humans, Male, Middle Aged, Mouth Neoplasms, Neoplasm Staging, Receptors, Immunologic, Risk Factors, Serine, Thymine, Genetic Variation, Case-Control Studies, Glycation End Products, Advanced, Sequence Deletion, Genetic Predisposition to Disease, Base Pairing, Polymorphism, Single Nucleotide, Gene-Environment Interaction, Carcinogenesis, Tobacco Use
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