SDF-1alpha G801A polymorphism predicts lymph node metastasis in stage T3 colorectal cancer.
BACKGROUND
The SDF-1/CXCR4 axis plays an important role in cancer metastasis. SDF1alpha genetic polymorphisms, including SDF1alpha-G801A, have been associated with increased cancer risk and may be predictive of distant metastasis. The present study compared the frequency of 6 SDF1alpha single-nucleotide polymorphisms (SNPs) in patients with colorectal cancer (CRC) with and without lymph node (LN) metastasis and determined whether fibroblasts with different SDF-1alpha 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 SDF1alpha-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-1alpha 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-1alpha neutralizing antibody.


CONCLUSIONS
The SDF1alpha-G801A polymorphism may increase expression of SDF-1alpha mRNA and be a predictive marker of lymph node metastasis in colorectal cancer.
Chang
Shih-Ching
SC
Division of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan.
Lin
Pei-Ching
PC
Yang
Shung-Haur
SH
Wang
Huann-Sheng
HS
Li
Anna Fen-Yau
AF
Lin
Jen-Kou
JK
D000368:Aged; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000235:genetics* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018572:Disease-Free Survival; D005347:Fibroblasts / Q000378:metabolism; D005838:Genotype; D006801:Humans; D008207:Lymphatic Metastasis; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014945:Wound Healing
D054377:Chemokine CXCL12; D012333:RNA, Messenger