VEGF polymorphisms in early cervical cancer susceptibility, angiogenesis, and survival.
OBJECTIVE
Vascular endothelial growth factor (VEGF) plays an important role in cervical carcinogenesis. We hypothesized that VEGF genetic polymorphisms may affect cancer susceptibility, angiogenesis, and survival in patients with early cervical cancer.


METHODS
Among 215 healthy subjects and 199 early cervical cancer patients who were treated with surgical resection, we specifically investigated four genetic polymorphisms within the VEGF gene (-2578C>A, -460 T>C, +405G>C, and +936C>T). VEGF and CD31 microvessel density (MVD) were measured using tissue microarrays constructed from 117 patients who had available tissue.


RESULTS
Risk of cervical cancer was decreased in subjects with the VEGF -2578A/A genotype (adjusted OR=0.39, 95% CI 0.16-0.96). Angiogenesis measured by CD31 MVD was significantly decreased in patients with the VEGF +405C/C genotype and VEGF -2578C - -460 T - +405C haplotype (recessive model; adjusted OR=0.32, 95% CI 0.11-0.99, equally). Moreover, VEGF +405C/C and VEGF -2578C - -460 T - +405C haplotype were significantly related to shorter disease-free survival (adjusted HR=3.18, 95% CI 1.13-8.94, equally) and overall survival (adjusted HR=8.86, 95% CI 1.40-56.08, equally) by multiple Cox regression analysis.


CONCLUSIONS
Polymorphisms of VEGF genes may affect cancer susceptibility and survival of early cervical cancer by modulating tumor angiogenesis. Prospective study among homogeneously treated patients is warranted.
Kim
Yun Hwan
YH
Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea.
Kim
Min A
MA
Park
In-Ae
IA
Park
Woong-Yang
WY
Kim
Jae Weon
JW
Kim
Seung Cheol
SC
Park
Noh-Hyun
NH
Song
Yong-Sang
YS
Kang
Soon-Beom
SB
D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000235:genetics / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D015996:Survival Rate; D002583:Uterine Cervical Neoplasms / Q000098:blood supply* / Q000235:genetics* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A