Role of genetic polymorphisms in tumour angiogenesis

Balasubramanian, Sabapathy P; Brown, Nicola J.; Reed, Malcolm

doi:10.1038/sj.bjc.6600625

Cited by 76 publications

(50 citation statements)

References 80 publications

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“…1 VEGF is strongly expressed in human solid tumours 2 and plays an important role in their pathogenesis. 3 There is evidence that tumours can promote VEGF production in adjacent stroma, which in turn predisposes to further tumour growth.…”

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Influence of VEGF‐A gene variation and protein levels in breast cancer susceptibility and severity

Balasubramanian

Cox

Cross

et al. 2007

Intl Journal of Cancer

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Vascular endothelial growth factor‐A (VEGF‐A) plays an important role in tumour angiogenesis and cancer progression. VEGF gene variation may influence VEGF levels and therefore cancer susceptibility and progression. We studied the role of VEGF single nucleotide polymorphisms and haplotypes in breast cancer susceptibility and severity. We also studied the relationships of VEGF SNPs with circulating VEGF levels in healthy volunteers and protein expression in breast cancers. Single nucleotide polymorphisms (SNPs) in the regulatory regions of the VEGF gene were genotyped by high throughput methods in ∼500 breast cancer cases and 500 appropriate controls. Haplotype frequencies were inferred using methods based on the Expectation Maximisation algorithm. The effect of VEGF genotypes on serum and plasma VEGF levels were studied in another cohort of healthy individuals. A semi‐quantitative assessment of VEGF protein expression on tissue micro arrays (TMA) constructed from ∼300 breast cancer samples was performed and compared with VEGF genotypes and with histopathological parameters and survival in breast cancer. The −460T/+405C/−7C/936C haplotype in the VEGF gene was found to be associated with decreased breast cancer risk (p = 0.029). The −7C>T polymorphism may influence overall breast cancer survival (p = 0.027). Individual polymorphisms however did not affect breast cancer susceptibility. There was no association between the individual polymorphisms and circulating VEGF levels in healthy volunteers and VEGF expression on the breast cancer micro array. VEGF expression in breast cancers was however associated with high grade (p = 0.002) and ER negative tumours (p = 0.03). © 2007 Wiley‐Liss, Inc.

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Influence of VEGF‐A gene variation and protein levels in breast cancer susceptibility and severity

Balasubramanian

Cox

Cross

et al. 2007

Intl Journal of Cancer

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“…Genetic alterations, such as point mutations, have been identified in FGFR genes and have been linked to developmental defects as well as neoplastic degeneration (Balasubramanian et al, 2002). Mutations in the FGFR1 and FGFR2 genes have been shown to cause craniosynostotic aberrations such as Apert-, Pfeiffer-, Jackson-, Weiss-and Crouzon syndrome (Muenke and Schell, 1995).…”

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FGFR4 Arg388 allele correlates with tumour thickness and FGFR4 protein expression with survival of melanoma patients

et al. 2006

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A single nucleotide polymorphism in the gene for FGFR4 (ÀArg388) has been associated with progression in various types of human cancer. Although fibroblast growth factors (FGFs) belong to the most important growth factors in melanoma, expression of FGF receptor subtype 4 has not been investigated yet. In this study, the protein expression of this receptor was analysed in 137 melanoma tissues of different progression stages by immunohistochemistry. FGFR4 protein was expressed in 45% of the specimens and correlated with pTNM tumour stages (UICC, P ¼ 0.023 and AJCC, P ¼ 0.046), presence of microulceration (P ¼ 0.009), tumour vascularity (P ¼ 0.001), metastases (P ¼ 0.025), number of primary tumours (P ¼ 0.022), overall survival (P ¼ 0.047) and disease-free survival (P ¼ 0.024). Furthermore, FGFR4 Arg388 polymorphism was analysed in 185 melanoma patients by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The Arg388 allele was detected in 45% of the melanoma patients and was significantly associated with tumour thickness (by Clark's level of invasion (P ¼ 0.004) and by Breslow in mm (P ¼ 0.02)) and the tumour subtype nodular melanoma (P ¼ 0.002). However, there was no correlation of the FGFR4 Arg388 allele with overall and disease-free survival. In conclusion, the Arg388 genotype and the protein expression of FGFR4 may be potential markers for progression of melanoma.

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“…The allele and genotype distributions of the polymorphism were in close agreement with those previously published for healthy Caucasian individuals. [8,11,12,[15][16][17][18][19][20][21][22] In a previous study among 500 Caucasian breast cancer cases and 500 controls, Krippl et al have shown a decreased risk of breast cancer in individuals who were +936 T allele carriers. [9] However, the genotypes in patients did not follow the Hardy-Weinberg equilibrium.…”

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confidence: 99%

“…In another study, no association between the +936(C/T) polymorphism and risk to breast cancer among 862 cases and 713 controls could be observed. [21] Here, we did a case-control study of 75 women with breast cancer. We observed no differences in the allele or genotype frequencies between breast cancer case and control groups, (odds ratio, 1.26; 95% confidence interval, 0.50-1.00; P = 0.715).…”

Section: Discussionmentioning

confidence: 99%

Clinical profile and role of VEGF-c polymorphism in prognosis and management of breast cancer

Singh

Yadav

Singh

et al. 2017

Int J Mol Immuno Oncol.

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Purpose: Angiogenesis is a necessary step in tumor growth and metastasis. Vascular endothelial growth factor (VEGF-c) is a major mediator of breast cancer angiogenesis. Therefore, we investigated the association of polymorphism in the VEGF-c gene with breast cancer risk and prognostic characteristics of the tumors in a case-control study. Experimental Design: We examined one polymorphism in the VEGF-c gene (+936C/T) in 75 breast cancer cases and 75 control from Kanpur, Uttar Pradesh, India and adjacent areas together with geographically selected controls. Results: None of the polymorphism or any haplotype was significantly associated with either breast cancers. Our study suggests that the +936C/T polymorphism is unlikely to be associated with breast cancer. We also analyzed the cases for genotypes or haplotypes that associated with tumor characteristics. The genotypes and haplotypes were not related with other tumor characteristics such as regional or distant metastasis, stage at diagnosis, or dietary history. Conclusions: Although none of the polymorphisms studied in the VEGF-c gene was found to influence susceptibility to breast cancer significantly, some of the VEGF-c genotypes and haplotypes may influence tumor growth through an altered expression of VEGF-c and tumor angiogenesis.

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Role of genetic polymorphisms in tumour angiogenesis

Cited by 76 publications

References 80 publications

Influence of VEGF‐A gene variation and protein levels in breast cancer susceptibility and severity

Influence of VEGF‐A gene variation and protein levels in breast cancer susceptibility and severity

FGFR4 Arg388 allele correlates with tumour thickness and FGFR4 protein expression with survival of melanoma patients

Clinical profile and role of VEGF-c polymorphism in prognosis and management of breast cancer

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