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01.10.2010 | Translational Research and Biomarkers | Ausgabe 10/2010

Annals of Surgical Oncology 10/2010

Polymorphisms in Apoptosis-Related Genes and Survival of Patients with Early-Stage Non-Small-Cell Lung Cancer

Zeitschrift:
Annals of Surgical Oncology > Ausgabe 10/2010
Autoren:
MD Eung Bae Lee, PhD Hyo-Sung Jeon, MD Seung Soo Yoo, MS Yi Young Choi, MS Hyo-Gyoung Kang, MD Sukki Cho, MD Sung-Ick Cha, PhD Jin Eun Choi, MD Tae-In Park, MD Byung-Heon Lee, MD Rang-Woon Park, MD In-San Kim, MD Young Mo Kang, MD Chang Ho Kim, MD Sanghoon Jheon, MD Tae Hoon Jung, MD Jae Yong Park
Wichtige Hinweise
Eung Bae Lee, Hyo-Sung Jeon have contributed equally to this study.

Abstract

Purpose

This study was conducted to determine the association between single-nucleotide polymorphisms (SNPs) in apoptosis-related genes and survival outcomes of patients with early-stage non-small-cell lung cancer (NSCLC).

Methods

Three hundred ten consecutive patients with surgically resected NSCLC were enrolled. Twenty-five SNPs in 17 apoptosis-related genes were genotyped by a sequenome mass spectrometry-based genotyping assay. The genotype associations with overall survival (OS) and disease-free survival (DFS) were analyzed.

Results

Three SNPs (TNFRSF10B rs1047266, TNFRSF1A rs4149570, and PPP1R13L rs1005165) were significantly associated with survival outcomes on multivariate analysis. When the three SNPs were combined, OS and DFS were decreased as the number of bad genotypes increased (P trend for OS and DFS = 7 × 10−5 and 1 × 10−4, respectively). Patients with one bad genotype, and patients with two or three bad genotypes had significantly worse OS and DFS compared with those with no bad genotypes [adjusted hazard ratio (aHR) for OS = 2.27, 95% confidence interval (CI) = 1.22–4.21, P = 0.01, aHR for DFS = 1.74, 95% CI = 1.08–2.81, P = 0.02; aHR for OS = 4.11, 95% CI = 2.03–8.29, P = 8 × 10−5; and aHR for DFS = 2.89, 95% CI = 1.64–5.11, P = 3 × 10−4, respectively].

Conclusion

Three SNPs in apoptosis-related genes were identified as possible prognostic markers of survival in patients with early-stage NSCLC. The SNPs, and particularly their combined genotypes, can be used to identify patients at high risk for poor disease outcome.

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