A polymorphism in the angiogenesis inhibitor, endostatin, in multiple myeloma

Ortega, Manoela Marques; Nascimento, Helvia; Teori, Maria T.; Costa, Fernando Ferreira; Lima, Carmen Sílvia Passos

doi:10.1016/s0145-2126(02)00218-7

Cited by 12 publications

(13 citation statements)

References 5 publications

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“…In a casecontrol study including 181 prostate cancer cases and 198 non-cancer individuals, we observed that the heterozygous N104 individuals have a 2.5 times increased chance of developing prostate cancer as compared with homozygous D104 subjects (Iughetti et al 2001). However, this association was not confirmed by us in another sample (data not published) as well as by others including different solid tumors (Ortega et al 2003, Liu et al 2003, Nascimento et al 2004, Macpherson et al 2004. It is possible that the variation of the genotypic frequencies observed in our original report just represent racial stratification.…”

Section: Polymorphic Changescontrasting

confidence: 57%

Mutations in collagen 18A1 (COL18A1) and their relevance to the human phenotype

Passos‐Bueno

Suzuki

Armelin‐Correa

et al. 2006

An. Acad. Bras. Ciênc.

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Collagen XVIII, a proteoglycan, is a component of basement membranes (BMs). There are three distinct isoforms that differ only by their N-terminal, but with a specific pattern of tissue and developmental expression. Cleavage of its C-terminal produces endostatin, an inhibitor of angiogenesis. In its N-terminal, there is a frizzled motif which seems to be involved in Wnt signaling. Mutations in this gene cause Knobloch syndrome (KS), an autosomal recessive disorder characterized by vitreoretinal and macular degeneration and occipital encephalocele. This review discusses the effect of both rare and polymorphic alleles in the human phenotype, showing that deficiency of one of the collagen XVIII isoforms is sufficient to cause KS and that null alleles causing deficiency of all collagen XVIII isoforms are associated with a more severe ocular defect. This review besides illustrating the functional importance of collagen XVIII in eye development and its structure maintenance throughout life, it also shows its role in other tissues and organs, such as nervous system and kidney.

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Section: Polymorphic Changescontrasting

confidence: 57%

Mutations in collagen 18A1 (COL18A1) and their relevance to the human phenotype

Passos‐Bueno

Suzuki

Armelin‐Correa

et al. 2006

An. Acad. Bras. Ciênc.

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“…The poor association that we have found is not without precedent in other cancers. Similar studies in patients with leukemia 36 and multiple myeloma 37 revealed no association between the endostatin D104N mutation and the incidence of those diseases. Thus, the natural histories of neither solid tumor nor hematological diseases appear to be affected by the D104N endostatin mutation.…”

Section: Discussionmentioning

confidence: 64%

Genotyping and functional analysis of the D104N variant of human endostatin

MacPherson¹,

Singh²,

Bennett³

et al. 2004

Cancer Biology & Therapy

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KEY WORDSendostatin, prostate cancer, angiogenesis, single nucleotide polymorphism ABBREVIATIONS AIPCandrogen independent prostate cancer HUVEC human umbilical vein endothelial cell HSPG heparin sulfate proteoglycan SNP single nucleotide polymorphism ACKNOWLEDGEMENTSWe wish to thank Andrada Tomoaia-Cotisel for technical assistance, Erin Lepper for predictive structural modeling and Martijn Gebbink for helpful correspondence. Research Paper Genotyping and Functional Analysis of the D104N Variant of Human Endostatin ABSTRACTEndostatin is an endogenous inhibitor of angiogenesis derived from the extracellular matrix protein collagen XVIII. It has been reported that a variation at the 104 position (D104N) of human endostatin is associated with an increased risk of prostate cancer, potentially indicating that this protein variant is less active as an anti-angiogenic agent. Herein we reported the results of genotyping 389 patients with androgen independent prostate cancer (AIPC) and 352 normal control individuals for D104N endostatin. There was no significant association between the frequency of 104N endostatin and the incidence of AIPC in either Caucasian or African American patients compared to controls (15% Caucasian AIPC versus 13.7% in Caucasian controls, p = 0.79; 7.4% African American AIPC versus 5.6% in African American controls, p = 0.64). Actuarial analysis revealed no statistically significant association between incidence of the DN heterozygous genotype and survival (p = 0.62 by logrank test). To study the functional significance of the D104N conversion, we have expressed and purified insoluble recombinant human 104D and 104N endostatin and compared their respective activities in human umbilical vein endothelial cell (HUVEC) tube formation assays. The 104N variant of human endostatin inhibited HUVEC tube formation at least as well as the wild-type form. We concluded that the D104N variation in human endostatin is neither clinically relevant nor suitable as a pharmacogenomic endpoint to assess the risk for developing AIPC.

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“…It is thought that the mutant molecule is stable but might impair Endostatin-induced angiogenesis inhibition by mechanisms that are still not clear [17]. Presence of the mutant allele results in a 2.5 times increased risk of prostate cancer [17], whereas in multiple myeloma there is no association with increased risk[18]. …”

Section: Introductionmentioning

confidence: 99%

Endostatin gene variation and protein levels in breast cancer susceptibility and severity

et al. 2007

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Background: Endostatin is a potent endogenous anti-angiogenic agent which inhibits tumour growth. A non-synonymous coding polymorphism in the Endostatin gene is thought to affect Endostatin activity. We aimed to determine the role of this Endostatin polymorphism in breast cancer pathogenesis and any influence on serum Endostatin levels in healthy volunteers. Endostatin protein expression on a breast cancer micro array was also studied to determine any relationship to genotype and to breast cancer prognosis.

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A polymorphism in the angiogenesis inhibitor, endostatin, in multiple myeloma

Cited by 12 publications

References 5 publications

Mutations in collagen 18A1 (COL18A1) and their relevance to the human phenotype

Mutations in collagen 18A1 (COL18A1) and their relevance to the human phenotype

Genotyping and functional analysis of the D104N variant of human endostatin

Endostatin gene variation and protein levels in breast cancer susceptibility and severity

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