Impacts of CA9 Gene Polymorphisms and Environmental Factors on Oral-Cancer Susceptibility and Clinicopathologic Characteristics in Taiwan
Journal
PLoS ONE
Journal Volume
7
Journal Issue
12
Pages
e51051
Date Issued
2012
Author(s)
Abstract
Background: In Taiwan, oral cancer has causally been associated with environmental carcinogens. Carbonic anhydrase 9 (CA9) is reportedly overexpressed in several types of carcinomas and is generally considered a marker of malignancy. The current study explored the combined effect of CA9 gene polymorphisms and exposure to environmental carcinogens on the susceptibility of developing oral squamous cell carcinoma (OSCC) and the clinicopathological characteristics of the tumors. Methodology and Principal Findings: Four single-nucleotide polymorphisms (SNPs) of the CA9 gene from 462 patients with oral cancer and 519 non-cancer controls were analyzed by a real-time polymerase chain reaction (PCR). While the studied SNPs (CA9 rs2071676, rs3829078, rs1048638 and +376 Del) were not associated with susceptibility to oral cancer, the GAA haplotype of 3 CA9 SNPs (rs2071676, rs3829078, and rs1048638) was related to a higher risk of oral cancer. Moreover, the four CA9 SNPs combined with betel quid chewing and/or tobacco consumption could robustly elevate susceptibility to oral cancer. Finally, patients with oral cancer who had at least one G allele of CA9 rs2071676 were at higher risk for developing lymph-node metastasis (p = 0.022), compared to those patients homozygous for AA. Conclusions: Our results suggest that the haplotype of rs2071676, rs3829078, and rs1048638 combined has potential predictive significance in oral carcinogenesis. Gene-environment interactions of CA9 polymorphisms, smoking, and betel-quid chewing might alter oral cancer susceptibility and metastasis. ? 2012 Chien et al.
SDGs
Other Subjects
carbonate dehydratase IX; adult; allele; article; CA9 gene; cancer risk; cancer susceptibility; carcinogenesis; controlled study; DNA polymorphism; environmental factor; female; gene sequence; genetic polymorphism; genotype environment interaction; haplotype; histopathology; homozygosity; human; human cell; lymph node metastasis; major clinical study; male; mouth cancer; oncogene; overall survival; real time polymerase chain reaction; sequence analysis; single nucleotide polymorphism; smokeless tobacco; Taiwan; Antigens, Neoplasm; Carbonic Anhydrases; Case-Control Studies; Confidence Intervals; Environment; Female; Gene Frequency; Genetic Predisposition to Disease; Haplotypes; Humans; Linkage Disequilibrium; Male; Middle Aged; Mouth Neoplasms; Odds Ratio; Polymorphism, Single Nucleotide; Risk Factors; Smoking; Taiwan; Nicotiana tabacum; Piper betel
Type
journal article