Genetic polymorphisms in OGG1 and their association with angiomyolipoma, a benign kidney tumor in patients with tuberous sclerosis

Samy L Habib, Elaine Danial, Subrata Nath, Jennifer Schneider, Christopher P. Jenkinson, Ravindranath Duggirala, Hanna E. Abboud, Farook Thameem

Research output: Contribution to journalArticle

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Abstract

The enzyme 8-oxoguanine glycosylase 1 (OGG1) repairs 8-oxo-2-deoxyguanosine residue (8-oxodG) an oxidatively damaged promutagenic base. Genetic variations in OGG1 gene have been shown to modulate DNA repair capacity and are related risk of tumor development. However, epidemiologic findings have been inconsistent. The purpose of this study is to determine whether genetic variants in OGG1 play a role in susceptibility to angiomyolipoma, a benign kidney tumor associated with tuberous sclerosis complex (TSC) patients. To identify genetic variations, all seven exons of the OGG1 gene were amplified by PCR and sequenced in 22 TSC patients with angiomyolipoma (cases) and 18 controls. By direct sequencing, we identified four missense mutations in OGG1: Arg(45)Gln, Ala(85)Ser, Arg(229)Gln and Ser(326)Cys. Genotypic association with angiomyolipoma was performed using the measured genotype approach as implemented in the variance component analytical tools. Association analysis showed the presence of significant association (p = 0.01) only between the Ser(326)Cys polymorphism of OGG1 and angiomyolipoma. We also assessed the presence of oxidative DNA damage in kidney section from normal healthy subjects, normal kidney tissue from TSC patients and kidney angiomyolipoma tissue from TSC patients by immunostaining for 8-oxodG. 8-OxodG staining was highly abundant in kidney angiomyolipoma tissue from TSC patients compared to weak staining in uninvolved tissue from the same TSC patients or normal kidney from healthy subjects. Taken together, our findings suggest that Ser(326)Cys variant of OGG1 may confer risk for development of angiomyolipomas by increasing oxidative DNA damage.

Original languageEnglish (US)
Pages (from-to)23-27
Number of pages5
JournalCancer Biology and Therapy
Volume7
Issue number1
StatePublished - Jan 2008

Fingerprint

Angiomyolipoma
Tuberous Sclerosis
Genetic Polymorphisms
Kidney
Neoplasms
DNA Damage
Healthy Volunteers
Staining and Labeling
Missense Mutation
8-hydroxyguanine
DNA Repair
Genes
Exons
Genotype
Polymerase Chain Reaction
Enzymes

Keywords

  • 8-oxodG
  • Angiomyolipoma
  • OGG1
  • SNPs
  • TSC2

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Habib, S. L., Danial, E., Nath, S., Schneider, J., Jenkinson, C. P., Duggirala, R., ... Thameem, F. (2008). Genetic polymorphisms in OGG1 and their association with angiomyolipoma, a benign kidney tumor in patients with tuberous sclerosis. Cancer Biology and Therapy, 7(1), 23-27.

Genetic polymorphisms in OGG1 and their association with angiomyolipoma, a benign kidney tumor in patients with tuberous sclerosis. / Habib, Samy L; Danial, Elaine; Nath, Subrata; Schneider, Jennifer; Jenkinson, Christopher P.; Duggirala, Ravindranath; Abboud, Hanna E.; Thameem, Farook.

In: Cancer Biology and Therapy, Vol. 7, No. 1, 01.2008, p. 23-27.

Research output: Contribution to journalArticle

Habib, SL, Danial, E, Nath, S, Schneider, J, Jenkinson, CP, Duggirala, R, Abboud, HE & Thameem, F 2008, 'Genetic polymorphisms in OGG1 and their association with angiomyolipoma, a benign kidney tumor in patients with tuberous sclerosis', Cancer Biology and Therapy, vol. 7, no. 1, pp. 23-27.
Habib, Samy L ; Danial, Elaine ; Nath, Subrata ; Schneider, Jennifer ; Jenkinson, Christopher P. ; Duggirala, Ravindranath ; Abboud, Hanna E. ; Thameem, Farook. / Genetic polymorphisms in OGG1 and their association with angiomyolipoma, a benign kidney tumor in patients with tuberous sclerosis. In: Cancer Biology and Therapy. 2008 ; Vol. 7, No. 1. pp. 23-27.
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