Polymorphisms in the FAS and FASL Genes and Survival of Early Stage Non–small Cell Lung Cancer
- Jae Yong Park1,2,
- Won-Kee Lee3,
- Duk-Ku Jung2,
- Jin-Eun Choi2,
- Tae-In Park4,
- Eung-Bae Lee5,
- Sukki Cho5,
- Ji-Young Park4,
- Sung-Ick Cha1,
- Chang-Ho Kim1,
- Sin Kam3,
- Tae Hoon Jung1 and
- Sanghoon Jheon6
- Authors' Affiliations: Departments of 1Internal Medicine, 2Biochemistry, 3Preventive Medicine, 4Pathology, and 5Thoracic Surgery, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; and 6Department of Thoracic and Cardiovascular Surgery, Seoul National University School of Medicine, Seoul, Republic of Korea
- Requests for reprints:
Jae Yong Park, Department of Internal Medicine, Kyungpook National University Hospital, Samduk 2Ga 50, Daegu, 700-412, Republic of Korea. Phone: 82-53-420-5536; Fax: 82-53-426-2046; E-mail: jaeyong{at}knu.ac.kr.
Abstract
Purpose: This study was conducted to investigate the impact of functional polymorphisms in the FAS and FASL genes on the survival of early stage non–small cell lung cancer (NSCLC) patients.
Experimental Design: Three hundred and thirty-eight consecutive patients with surgically resected NSCLC were enrolled. The FAS -1377G>A (rs2234767) and -670A>G (rs1800682) and FASL -844C>T (rs763110) polymorphisms were investigated. Immunohistochemistry was used to assess FAS protein expression in tumors. The genotype and haplotype associations with survival were analyzed using Cox proportional hazards model, Kaplan-Meier method, and the log-rank test.
Results: Patients with the GG and combined AG + GG genotypes of the FAS -670A>G locus had a significantly decreased survival when compared with patients with the AA genotype [adjusted hazard ratio = 1.71, 95% confidence interval (95% CI) = 1.06-2.77, and P = 0.03; and adjusted hazard ratio = 1.48, 95% CI = 1.01-2.20, and P = 0.047, respectively]. In addition, the FAS -1377G/-670G and -1377A/-670G haplotypes exhibited a significantly lower survival compared with the -1377G/-670A haplotype (adjusted hazard ratio = 1.87, 95% CI = 1.20-2.91, and P = 0.006; and adjusted hazard ratio = 1.31, 95% CI = 1.05-1.65, P = 0.02, respectively). Strongly positive FAS immunostaining was significantly less frequent in patients with the FAS -670 AG + GG genotype than in patients with the -670 AA genotype (4.5% versus 10.8%; P = 0.04).
Conclusion: The FAS -670A>G polymorphism may affect survival in early-stage NSCLC. The analysis of the FAS -670A>G polymorphism can help identify patients at high risk for a poor disease outcome.
Footnotes
-
Grant support: The National R&D Program for Cancer Control Ministry of Health and Welfare (0720550-2); the Regional Technology Innovation Program of the Ministry of Commerce, Industry and Energy (RTI04-01-01) of Republic of Korea; and the Brain Korea 21 Project in 2006.
-
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
-
- Accepted November 14, 2008.
- Received July 11, 2008.
- Revision received November 10, 2008.
