The association between hypoxia inducible factor-1α gene polymorphisms and increased susceptibility to oral cancer

Received 8 July 2009; received in revised form 20 July 2009; accepted 20 July 2009. published online 01 September 2009.

Summary

The aim of this study was to estimate the relations between hypoxia inducible factor-1α (HIF-1α) gene polymorphisms, C1772T and G1790A, to the susceptibility and clinicopathological status of oral cancer. A total of 521 subjects, including 347 controls and 174 oral cancer patients, were recruited in this study and subjected to polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to analyze the impact of these two polymorphic variants on oral cancer. A significant association between oral cancer susceptibility and G1790A polymorphism was demonstrated since individuals with heterozygotes, that is GA, had a higher risk for oral cancer, compared to GG genotypes after adjusting for other confounders (AOR=3.31; 95%CI=1.27–8.61). Compared to individuals with both C1772C and G1790G homozygotes, individuals with at least one of either C1772T or G1790A of HIF-1α gene had a risk of 2.17-folds (95% CI=1.0–4.75) to develop oral cancer. Moreover, results also revealed the presence of synergistic effect between gene polymorphisms of HIF-1α and environmental risk factors, such as tobacco and betel nut consumptions while there was no significant association between HIF-1α gene polymorphism and clinicopathological parameters of oral cancer. Genetic polymorphism, including C1772T and G1790A, of HIF-1α is an important factor for the susceptibility to oral cancer.

Keywords: Hypoxia inducible factor-1α, Single nucleotide polymorphism, Oral cancer, Tobacco consumption, Betel nut chewing

a Department of Otorhinolaryngology-Head and Neck Surgery, Changhua Christian Hospital, Changhua, Taiwan

b Mingdao University, Changhua, Taiwan

c School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan

d Department of Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan

e Department of Molecular and Cellular Medicine, Texas A&M University System Health Science Center, College Station, Texas, USA

f Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan

g Department of Otolaryngology, Show Chwan Memorial Hospital, Changhua, Taiwan

h Department of Radiation Oncology, Chung Shan Medical University Hospital, Taichung, Taiwan

i School of Nursing, College of Nursing, Chung Shan Medical University, Taichung, Taiwan

j Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan

Corresponding authors. Address: Institute of Medicine, Chung Shan Medical University, 110, Section 1, Chien-Kuo N. Road, Taichung, Taiwan, ROC. Tel.: +886 4 24739595x34253; fax: +886 4 24723229 (S.-F. Yang).

1 The first two authors contributed equally to this article.

PII: S1368-8375(09)00875-6

doi:10.1016/j.oraloncology.2009.07.015

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