Abstract
Background
Caveolin-1, which has been proposed as a candidate tumor suppressor, plays a regulatory role in several signaling pathways. The aim of this study was to evaluate the association between oral cancer susceptibility and Cav-1 genotypes. In this hospital-based case-control study, the association of Cav-1 polymorphisms with oral cancer risk in a central Taiwanese population was investigated.
Methods
Six hundred patients with oral cancer and 620 age- and sex-matched healthy control subjects were genotyped and analyzed by polymerase chain reaction–restriction fragment length polymorphism.
Results
There were significant differences between oral cancer and control groups in the distributions of their genotypes (P = 1.7 × 10−18 and 2.6 × 10−4) and allelic frequencies (P = 3.3 × 10−19 and 9.5 × 10−6) in the Cav-1 G14713A (rs3807987) and T29107A (rs7804372) polymorphisms, respectively. As for the combined genotype analysis, those who had GG/AT or GG/AA at Cav-1 G14713A/T29107A showed a 0.72-fold (95% confidence interval = 0.52–0.99) decreased risk of oral cancer compared to those with GG/TT, while those of any other combinations were of increased risk. The presence of metastasis was also correlated to both Cav-1 G14713A AA and Cav-1 T29107A TT genotypes.
Conclusions
Cav-1 is involved in oral cancer, the A allele of the Cav-1 G14713A is risky, the A allele of the Cav-1 T29107A is protective, and AA/TT on these two polymorphisms may be the most risky combined genotype for the development of oral cancer and may be novel risk markers for early detection and prediction of distant metastasis.
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References
Altekruse SF, Kosary CL, Krapcho M, et al. SEER Cancer Statistics Review, 1975–2007. Bethesda, MD: National Cancer Institute; 2010.
American Cancer Society. Cancer Facts and Figures, 2010. Atlanta, GA: American Cancer Society; 2010.
Department of Health, Taiwan. Cancer Registration System Annual Report. Taiwan: Department of Health; 2009.
Cohen AW, Hnasko R, Schubert W, Lisanti MP. Role of caveolae and caveolins in health and disease. Physiol Rev. 2004;84:1341–79.
Glenney JR Jr. Tyrosine phosphorylation of a 22-kDa protein is correlated with transformation by Rous sarcoma virus. J Biol Chem. 1989;264:20163–6.
Belanger MM, Roussel E, Couet J. Caveolin-1 is down-regulated in human lung carcinoma and acts as a candidate tumor suppressor gene. Chest. 2004;125:106S.
Wiechen K, Diatchenko L, Agoulnik A, et al. Caveolin-1 is down-regulated in human ovarian carcinoma and acts as a candidate tumor suppressor gene. Am J Pathol. 2001;159:1635–43.
Wiechen K, Sers C, Agoulnik A, et al. Down-regulation of caveolin-1, a candidate tumor suppressor gene, in sarcomas. Am J Pathol. 2001;158:833–9.
Yang G, Truong LD, Wheeler TM, Thompson TC. Caveolin-1 expression in clinically confined human prostate cancer: a novel prognostic marker. Cancer Res. 1999;59:5719–23.
Kato K, Hida Y, Miyamoto M, et al. Overexpression of caveolin-1 in esophageal squamous cell carcinoma correlates with lymph node metastasis and pathologic stage. Cancer. 2002;94:929–33.
Bau DT, Tseng HC, Wang CH, et al. Oral cancer and genetic polymorphism of DNA double strand break gene Ku70 in Taiwan. Oral Oncol. 2008;44:1047–51.
Chang CH, Wang RF, Tsai RY, et al. Significant association of XPD codon 312 single nucleotide polymorphism with bladder cancer susceptibility in Taiwan. Anticancer Res. 2009;29:3903–7.
Chiu CF, Tsai MH, Tseng HC, et al. A novel single nucleotide polymorphism in ERCC6 gene is associated with oral cancer susceptibility in Taiwanese patients. Oral Oncol. 2008;44:582–6.
Chiu CF, Tsai MH, Tseng HC, et al. A novel single nucleotide polymorphism in XRCC4 gene is associated with oral cancer susceptibility in Taiwanese patients. Oral Oncol. 2008;44:898–902.
Chiu CF, Wang CH, Wang CL, et al. A novel single nucleotide polymorphism in XRCC4 gene is associated with gastric cancer susceptibility in Taiwan. Ann Surg Oncol. 2008;15:514–8.
Hsu CF, Tseng HC, Chiu CF, et al. Association between DNA double strand break gene Ku80 polymorphisms and oral cancer susceptibility. Oral Oncol. 2009;45:789–93.
Wang HC, Chiu CF, Tsai RY, et al. Association of genetic polymorphisms of EXO1 gene with risk of breast cancer in Taiwan. Anticancer Res. 2009;29:3897–901.
Conde MC, Ramirez-Lorca R, Lopez-Jamar JM, et al. Genetic analysis of caveolin-1 and eNOS genes in colorectal cancer. Oncol Rep. 2006;16:353–9.
Han SE, Park KH, Lee G, Huh YJ, Min BM. Mutation and aberrant expression of caveolin-1 in human oral squamous cell carcinomas and oral cancer cell lines. Int J Oncol. 2004;24:435–40.
Shi L, Chen XM, Wang L, Zhang L, Chen Z. Expression of caveolin-1 in mucoepidermoid carcinoma of the salivary glands: correlation with vascular endothelial growth factor, microvessel density, and clinical outcome. Cancer. 2007;109:1523–31.
Acknowledgment
We thank Wen-Shin Chang, Hsiu-Min Hsieh, and the Tissue Bank of the China Medical University Hospital for their technical assistance. This study was supported by research grants from the China Medical University and Hospital (DMR-99-049, DOH99-TD-C-111-005) and the National Science Council (NSC 98-2320-B-039-010-MY3).
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The authors declare no conflict of interest.
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Bau, DT., Tsai, M.H., Tsou, YA. et al. The Association of Caveolin-1 Genotypes with Oral Cancer Susceptibility in Taiwan. Ann Surg Oncol 18, 1431–1438 (2011). https://doi.org/10.1245/s10434-010-1483-4
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DOI: https://doi.org/10.1245/s10434-010-1483-4