Polymorphisms in VEGF and IL-8 predict tumor recurrence in stage III colon cancer.
BACKGROUND
Identifying molecular markers for tumor recurrence is critical in successfully selecting patients with stage III colon cancer who are more likely to benefit from adjuvant chemotherapy. The present study analyzed a subset of 10 polymorphisms within eight genes involved in the tumor angiogenesis pathway and their impact on prognosis in stage III colon cancer patients treated with adjuvant chemotherapy.


METHODS
Blood samples were obtained from 125 patients with locally advanced colon cancer at University of Southern California medical facilities. DNA was extracted from peripheral blood and the genotypes were analyzed using PCR-restriction fragment length polymorphism and 5'-end [gamma-(33)P] ATP-labeled PCR protocols.


RESULTS
Polymorphisms in vascular endothelial growth factor (VEGF) (C+936T; P = 0.003, log-rank test) and interleukin-8 (IL-8) (T-251A; P = 0.04, log-rank test) were independently associated with risk of recurrence in stage III colon cancer patients. In combined analysis, grouping alleles into favorable versus nonfavorable alleles, high expression variants of VEGF C+936T and IL-8 T-251A were associated with a higher likelihood of developing tumor recurrence (P < 0.001).


CONCLUSIONS
High expression variants of VEGF C+936T and IL-8 T-251A were associated with shorter time to tumor recurrence, indicating that the analysis of angiogenesis-related gene polymorphisms may help to identify patient subgroups at high risk for tumor recurrence.
Division of Medical Oncology, University of SouthernCalifornia, Sharon A Carpenter Laboratory, Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, CA 90033, USA.
G
G
Lurje
W
W
Zhang
A M
AM
Schultheis
D
D
Yang
S
S
Groshen
A E
AE
Hendifar
H
H
Husain
M A
MA
Gordon
F
F
Nagashima
H M
HM
Chang
H-J
HJ
Lenz
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D003110:Colonic Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000098:blood supply / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000097:blood / Q000235:genetics; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
D004273:DNA, Neoplasm; D016209:Interleukin-8; D042461:Vascular Endothelial Growth Factor A; D005472:Fluorouracil