Genetic Polymorphism in a VEGF-Independent Angiogenesis Gene ANGPT1 and Overall Survival of Colorectal Cancer Patients after Surgical Resection

Authors

Jingyao Dai, Xijing Hospital, The Fourth Military Medical UniversityFollow
Shaogui Wan, Division of Population Science, Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson UniversityFollow
Feng Zhou, Tangdu Hospital, The Fourth Military Medical University
Ronald E. Myers, Division of Population Science, Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson UniversityFollow
Xu Guo, State Key Laboratory of Cancer Biology, Cell Engineering Research Center & Department of Cell Biology, The Fourth Military Medical UniversityFollow
Bingshan Li, Vanderbilt UniversityFollow
Xiaoying Fu, Division of Population Science, Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson UniversityFollow
Juan P. Palazzo, Department of Pathology, Thomas Jefferson UniversityFollow
Kefeng Dou, Xijing Hospital, The Fourth Military Medical UniversityFollow
Hushan Yang, Division of Population Science, Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson UniversityFollow
Jinliang Xing, State Key Laboratory of Cancer Biology, Cell Engineering Research Center & Department of Cell Biology, The Fourth Military Medical UniversityFollow

Document Type

Article

Publication Date

4-4-2012

Comments

This article has been peer reviewed and is published in PLoS One 2012, 7(4): e34758. The published version is available at DOI: 10.1371/journal.pone.0034758. © Public Library of Science

Abstract

Background

The VEGF-independent angiogenic signaling plays an important role in the development of colorectal cancer (CRC). However, its implication in the clinical outcome of CRC has not been reported. This study aimed to investigate the association between genetic variations in several major VEGF-independent signaling pathway genes and the overall survival of CRC patients.

Methods

Seven single nucleotide polymorphisms (SNPs) in four important VEGF-independent angiogenic genes (ANGPT1, AMOT, DLL4 and ENG) were genotyped in a Chinese population with 408 CRC patients.

Results

One SNP, rs1954727 in ANGPT1, was significantly associated with CRC overall survival. Compared to patients with the homozygous wild-type genotype of rs1954727, those with heterozygous and homozygous variant genotypes exhibited a favorable overall survival with a hazard ratio (HR) of 0.89 (95% confidence interval [CI] 0.55–1.43, P = 0.623), and 0.32 (95% CI 0.15–0.71, P = 0.005), respectively (P trend = 0.008). In stratified analysis, this association remained significant in patients receiving chemotherapy (P trend = 0.012), but not in those without chemotherapy. We further evaluated the effects of chemotherapy on CRC survival that was stratified by rs1954727 genotypes. We found that chemotherapy resulted in a significantly better overall survival in the CRC patients (HR = 0.44, 95% CI 0.26–0.75, P = 0.002), which was especially prominent in those patients with the heterozygous genotype of rs1954727 (HR = 0.45, 95%CI 0.22–0.92, P = 0.028).

Conclusion

Our data suggest that rs1954727 in ANGPT1 gene might be a prognostic biomarker for the overall survival of CRC patients, especially in those receiving chemotherapy, a finding that warrants validation in larger independent populations.

Recommended Citation

Dai, Jingyao; Wan, Shaogui; Zhou, Feng; Myers, Ronald E.; Guo, Xu; Li, Bingshan; Fu, Xiaoying; Palazzo, Juan P.; Dou, Kefeng; Yang, Hushan; and Xing, Jinliang, "Genetic Polymorphism in a VEGF-Independent Angiogenesis Gene ANGPT1 and Overall Survival of Colorectal Cancer Patients after Surgical Resection" (2012). Kimmel Cancer Center Faculty Papers. Paper 22.
https://jdc.jefferson.edu/kimmelccfp/22