© 2004 by Oxford University Press
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2004 Oxford University Press
ARTICLE |
Polymorphisms of Death Pathway Genes FAS and FASL in Esophageal Squamous-Cell Carcinoma
Affiliation of authors: Department of Etiology and Carcinogenesis, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Correspondence to: Professor Dongxin Lin, MD, Department of Etiology and Carcinogenesis, Cancer Institute, Chinese Academy of Medical Sciences, Beijing 100021, China (e-mail: dlin{at}public.bta.net.cn)
Background: The FAS receptor–ligand system is a key regulator of apoptotic cell death, and loss of FAS expression and gain of FAS ligand (FASL) expression play important roles in the development and progression of cancer. Single-nucleotide polymorphisms in the promoter region of the FAS (G or A at position –1377 [FAS –1377G/A] and A or G at position –670 [FAS –670A/G]) and FASL (T or C at position –844 [FASL –844T/C]) genes alter the transcriptional activity of these genes. We examined the association between these polymorphisms and risk of the development and metastasis of esophageal squamous-cell carcinoma. Methods: Genotypes of 588 case patients with esophageal squamous-cell carcinoma and 648 control subjects were determined by polymerase chain reaction–based restriction fragment length polymorphism. Associations with the risk of esophageal squamous-cell carcinoma were estimated by logistic regression. All statistical tests were two-sided. Results: We observed a statistically significantly increased risk of esophageal squamous-cell carcinoma associated with the FAS –1377AA (odds ratio [OR] = 1.79, 95% confidence interval [CI] = 1.29 to 2.48; P<.001) or FAS –670GG (OR = 1.72, 95% CI = 1.26 to 2.34; P<.001) genotype, which are in strong linkage disequilibrium compared with the FAS –1377GA or GG or the FAS –670AG or AA genotype, respectively. An increased risk of esophageal squamous-cell carcinoma was also associated with the FASL –844CC genotype (OR = 2.06, 95% CI = 1.64 to 2.59; P<.001) compared with the FASL –844CT or TT genotype. Gene–gene interactions of FAS and FASL polymorphisms increased the risk of esophageal squamous-cell carcinoma in a multiplicative manner (OR for the presence of both FAS –1377AA and FASL –844CC genotypes = 4.55, 95% CI = 2.75 to 7.48; P = .001, test for homogeneity). Statistically significant interactions were found between these polymorphisms in FAS and FASL and tobacco smoking. None of the polymorphisms was associated with risk of differentiation or metastasis of esophageal squamous-cell carcinoma at diagnosis. Conclusion: Genetic polymorphisms in the death pathway genes FAS and FASL appear to be associated with an increased risk of developing esophageal squamous-cell carcinoma.
CiteULike 
Connotea 
Del.icio.us What's this?
Correspondence about this Article
- Re: Polymorphisms of Death Pathway Genes FAS and FASL in Esophageal Squamous-Cell Carcinoma
- Peter Krippl, Uwe Langsenlehner, Wilfried Renner, Herwig Köppel, and Hellmut Samonigg
J Natl Cancer Inst 2004 96: 1478-1479.[Extract] [Full Text] [PDF]
- RESPONSE: Re: Polymorphisms of Death Pathway Genes FAS and FASL in Esophageal Squamous-Cell Carcinoma
- Tong Sun, Xiaoping Miao, Xuemei Zhang, and Dongxin Lin
J Natl Cancer Inst 2004 96: 1479.[Extract] [Full Text] [PDF]
This article has been cited by other articles:
|
|
 |
|
  M. Yang, T. Sun, L. Wang, D. Yu, X. Zhang, X. Miao, J. Liu, D. Zhao, H. Li, W. Tan, et al. Functional Variants in Cell Death Pathway Genes and Risk of Pancreatic Cancer Clin. Cancer Res., May 15, 2008; 14(10): 3230 - 3236. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. D. Crew, M. D. Gammon, M. B. Terry, F. F. Zhang, M. Agrawal, S. M. Eng, S. K. Sagiv, S. L. Teitelbaum, A. I. Neugut, and R. M. Santella Genetic polymorphisms in the apoptosis-associated genes FAS and FASL and breast cancer risk Carcinogenesis, December 1, 2007; 28(12): 2548 - 2551. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Pine, L. E. Mechanic, S. Ambs, E. D. Bowman, S. J. Chanock, C. Loffredo, P. G. Shields, and C. C. Harris Lung Cancer Survival and Functional Polymorphisms in MBL2, an Innate-Immunity Gene J Natl Cancer Inst, September 19, 2007; 99(18): 1401 - 1409. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Villa-Morales, J. Santos, E. Perez-Gomez, M. Quintanilla, and J. Fernandez-Piqueras A Role for the Fas/FasL System in Modulating Genetic Susceptibility to T-Cell Lymphoblastic Lymphomas Cancer Res., June 1, 2007; 67(11): 5107 - 5116. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Zhang, T. Sun, L. Xue, X. Han, B. Zhang, N. Lu, Y. Shi, W. Tan, Y. Zhou, D. Zhao, et al. Functional polymorphisms in FAS and FASL contribute to increased apoptosis of tumor infiltration lymphocytes and risk of breast cancer Carcinogenesis, May 1, 2007; 28(5): 1067 - 1073. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Zhivotovsky and S. Orrenius Carcinogenesis and apoptosis: paradigms and paradoxes Carcinogenesis, October 1, 2006; 27(10): 1939 - 1945. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Zhang, L.-E Wang, E. M. Sturgis, A. K. El-Naggar, W. K. Hong, C. I. Amos, M. R. Spitz, and Q. Wei Polymorphisms of FAS and FAS Ligand Genes Involved in the Death Pathway and Risk and Progression of Squamous Cell Carcinoma of the Head and Neck. Clin. Cancer Res., September 15, 2006; 12(18): 5596 - 5602. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Y. Park, J. M. Park, J. S. Jang, J. E. Choi, K. M. Kim, S. I. Cha, C. H. Kim, Y. M. Kang, W. K. Lee, S. Kam, et al. Caspase 9 promoter polymorphisms and risk of primary lung cancer Hum. Mol. Genet., June 15, 2006; 15(12): 1963 - 1971. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K W Chan, P Y Lee, A K Y Lam, S Law, J Wong, and G Srivastava Clinical relevance of Fas expression in oesophageal squamous cell carcinoma J. Clin. Pathol., January 1, 2006; 59(1): 101 - 104. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Sun, Y. Zhou, H. Li, X. Han, Y. Shi, L. Wang, X. Miao, W. Tan, D. Zhao, X. Zhang, et al. FASL -844C polymorphism is associated with increased activation-induced T cell death and risk of cervical cancer J. Exp. Med., October 3, 2005; 202(7): 967 - 974. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X Zhang, X Miao, T Sun, W Tan, S Qu, P Xiong, Y Zhou, and D Lin Functional polymorphisms in cell death pathway genes FAS and FASL contribute to risk of lung cancer J. Med. Genet., June 1, 2005; 42(6): 479 - 484. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Hu, C. Wang, Y. Hu, H. H. Yang, C. Giffen, Z.-Z. Tang, X.-Y. Han, A. M. Goldstein, M. R. Emmert-Buck, K. H. Buetow, et al. Genome-Wide Association Study in Esophageal Cancer Using GeneChip Mapping 10K Array Cancer Res., April 1, 2005; 65(7): 2542 - 2546. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Krippl, U. Langsenlehner, W. Renner, H. Koppel, and H. Samonigg Re: Polymorphisms of Death Pathway Genes FAS and FASL in Esophageal Squamous-Cell Carcinoma J Natl Cancer Inst, October 6, 2004; 96(19): 1478 - 1479. [Full Text] [PDF]
|
|
|
|
|
|
T. Sun, X. Miao, X. Zhang, and D. Lin RESPONSE: Re: Polymorphisms of Death Pathway Genes FAS and FASL in Esophageal Squamous-Cell Carcinoma J Natl Cancer Inst, October 6, 2004; 96(19): 1479 - 1479. [Full Text] [PDF]
|
|