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01-08-2009 | Translational Research and Biomarkers

SDF-1α G801A Polymorphism Predicts Lymph Node Metastasis in Stage T3 Colorectal Cancer

Authors: Shih-Ching Chang, MD, PhD, Pei-Ching Lin, MD, Shung-Haur Yang, MD, PhD, Huann-Sheng Wang, MD, Anna Fen-Yau Li, MD, PhD, Jen-Kou Lin, MD, PhD

Published in: Annals of Surgical Oncology | Issue 8/2009

Abstract

Background

The SDF-1/CXCR4 axis plays an important role in cancer metastasis. SDF1α genetic polymorphisms, including SDF1α-G801A, have been associated with increased cancer risk and may be predictive of distant metastasis. The present study compared the frequency of 6 SDF1α single-nucleotide polymorphisms (SNPs) in patients with colorectal cancer (CRC) with and without lymph node (LN) metastasis and determined whether fibroblasts with different SDF-1α genotypes influenced cancer cell proliferation and migration.

Methods

The study enrolled 424 patients with primary T3 stage CRC, with and without lymph node metastasis, and a median follow-up of 48 months. The polymerase chain reaction-sequence specific primers (PCR-SSP) technique was used to identify polymorphisms. Fibroblasts were harvested from 14 patients with stage II CRC and fibroblast-mediated enhancement of cancer cell proliferation and migration was evaluated.

Results

Only the SDF1α-G801A polymorphism was associated with LN metastasis. The frequency of GA/AA genotypes was significantly higher in patients with LN metastasis (54.8%) than in patients without LN metastasis (40.7%). In the latter group, disease-free survival was shorter in patients with the GA/AA genotype (74%) than in patients with the GG genotype (87.6%). In patients with LN metastasis, disease-free survival was similar regardless of genotype. Expression of SDF-1α mRNA in GA/AA fibroblasts was three times that in GG fibroblasts. GA/AA (but not GG) fibroblasts enhanced colon cancer cell (HCT116) proliferation and migration. These effects were blocked by an SDF-1α neutralizing antibody.

Conclusions

The SDF1α-G801A polymorphism may increase expression of SDF-1α mRNA and be a predictive marker of lymph node metastasis in colorectal cancer.

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Title: SDF-1α G801A Polymorphism Predicts Lymph Node Metastasis in Stage T3 Colorectal Cancer
Authors: Shih-Ching Chang, MD, PhD
Pei-Ching Lin, MD
Shung-Haur Yang, MD, PhD
Huann-Sheng Wang, MD
Anna Fen-Yau Li, MD, PhD
Jen-Kou Lin, MD, PhD
Publication date: 01-08-2009
Publisher: Springer-Verlag
Published in: Annals of Surgical Oncology / Issue 8/2009
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-009-0501-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

SDF-1α G801A Polymorphism Predicts Lymph Node Metastasis in Stage T3 Colorectal Cancer

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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