IngentaConnect Heparanase gene haplotype (CGC) is associated with stage of disea...

Authors: Ralph, Shirley; Brenchley, Paul E. C.¹; Summers, Angela¹; Rosa, Daniela D.²; Swindell, Ric²; Jayson, Gordon C.²

Source: Cancer Science, Volume 98, Number 6, June 2007 , pp. 844-849(6)

Publisher: Blackwell Publishing

Abstract:

Heparanase (HSPE-1) and vascular endothelial growth factor (VEGF), proangiogenic growth factors, play important roles in the metastatic biology of ovarian cancer. The aim of the present study was to test for association between single nucleotide polymorphisms (SNPs) in HSPE-1 and VEGF and outcome in ovarian cancer. A mutational analysis was performed on the coding sequence of the HSPE-1 gene to define high-frequency SNPs. HSPE-1 polymorphisms, together with two SNPs in the VEGF gene, were studied in 136 patients with ovarian cancer. Patients were categorized into two groups, those with FIGO stages 1 and 2 (group 1) and those with stages 3 and 4 (group 2). We identified 10 polymorphisms in the HSPE-1 gene, those in introns 2, 3 and 5b, and exons 8, 13a and 13b occurring at a minor allele frequency of ≥10%. There was an increase in frequency of those individuals with a genotype that carried at least one copy of the intron 2 (C), exon 8 (G), exon 13a (C) haplotype (CGC) in group 2. Specifically there were 24% with this haplotype in group 2 versus 5% in group 1 (P = 0.0184, odds ratio 5.986, 95% confidence interval 1.340-26.752). Most of this association was captured by the intron 2 genotype, where carriage of the C allele was associated with stage (P = 0.0148, odds ratio 6.524, 95% confidence interval 1.401-27.921). There was no association between VEGF SNPs and stage of disease. The CGC HSPE-1 haplotype associates with stage in ovarian cancer. This haplotype may affect splicing of the HSPE-1 gene, as in silico it alters the presence of a splicing motif. (Cancer Sci 2007; 98: 844-849)

Document Type: Research article

DOI: 10.1111/j.1349-7006.2007.00461.x

Affiliations: 1: Renal Research Laboratories, Manchester Institute of Nephrology and Transplantation, CMMC University Hospital Trust, Oxford Road, Manchester M13 9WL; 2: University Department of Medical Oncology, Christie Hospital, Manchester M20 4BX, UK

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Heparanase gene haplotype (CGC) is associated with stage of disease in patients with ovarian carcinoma