Searching for association of the CAG repeat polymorphism in the mitochondrial DNA polymerase gamma gene (POLG) with colorectal cancer

• Authors: Katarzyna Linkowska , Arkadiusz Jawień , Andrzej Marszałek , Katarzyna Skonieczna , Tomasz Grzybowski
• Languages of publication: EN

Abstracts

EN

Mitochondrial DNA polymerase gamma (POLG) is the only DNA polymerase involved in maintaining the mitochondrial genome. Recent studies demonstrated an association of CAG repeat polymorphism in the second exon of POLG gene with the risk of cancer. We investigated the CAG repeat variability in the POLG gene in tumor and non-tumor tissues from colorectal cancer patients and in DNA samples isolated from blood obtained from age-matched healthy persons. Somatically occuring CAG-repeat alterations in cancer tissues have been observed in 10% of patients, but no association has been found between the CAG repeat variants in the POLG gene and colorectal cancer risk.

Keywords

EN

POLG gene; CAG repeat; colorectal cancer; somatic mutations

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2015
• Volume: 62
• Issue: 3
• Pages: 625-627

Dates

published

2015

received

2014-11-11

revised

2015-07-06

accepted

2015-07-31

(unknown)

2015-08-28

Contributors

author

Katarzyna Linkowska

• The Nicolaus Copernicus University, Ludwik Rydygier Collegium Medicum, Institute of Forensic Medicine, Department of Molecular and Forensic Genetics, Bydgoszcz, Poland

author

Arkadiusz Jawień

• The Nicolaus Copernicus University, Ludwik Rydygier Collegium Medicum, Chair of Vascular Surgery and Angiology, Bydgoszcz, Poland

author

Andrzej Marszałek

• The Nicolaus Copernicus University, Ludwik Rydygier Collegium Medicum, Chair & Department of Clinical Pathomorphology, Bydgoszcz, Poland

author

Katarzyna Skonieczna

• The Nicolaus Copernicus University, Ludwik Rydygier Collegium Medicum, Institute of Forensic Medicine, Department of Molecular and Forensic Genetics, Bydgoszcz, Poland

author

Tomasz Grzybowski

• The Nicolaus Copernicus University, Ludwik Rydygier Collegium Medicum, Institute of Forensic Medicine, Department of Molecular and Forensic Genetics, Bydgoszcz, Poland

References

• Azrak S, Ayyasamy V, Zirpoli G, Ambrosone C, Bandera EV, Bovbjerg DH, Jandorf L, Ciupak G, Davis W, Pawlish KS, Liang P, Singh K (2012) CAG repeat variants in the POLG1 gene encoding mtDNA polymerase-gamma and risk of breast cancer in African-American women. PLoS One 7: e29548.
• Blomberg Jensen M, Leffers H, Petersen JH, Daugaard G, Skakkebaek NE, Rajpert-De Meyts E (2008) Association of the polymorphism of the CAG repeat in the mitochondrial DNA polymerase gamma gene (POLG) with testicular germ-cell cancer. Ann Oncol 19: 1910-1914.
• Boland CR, Goel A (2010) Microsatellite instability in colorectal cancer. Gastroenterology 138: 2073-2087 e2073.
• Euro L, Farnum GA, Palin E, Suomalainen A, Kaguni LS (2011) Clustering of Alpers disease mutations and catalytic defects in biochemical variants reveal new features of molecular mechanism of the human mitochondrial replicase, Pol gamma. Nucleic Acids Res 39: 9072-9084.
• Malyarchuk BA, Papuga M, Grzybowski T, Rogozin IB, Wozniak M, Derenko MV, Rychkov SY, Czarny J, Zakharov IA, Miścicka-Sliwka D (2005) Low variability of the POLG (CAG)n repeat in north Eurasian populations. Hum Biol 77: 355-365.
• Nowak R, Zub R, Skoneczna I, Sikora K, Ligaj M (2005) CAG repeat polymorphism in the DNA polymerase gamma gene in a Polish population: an association with testicular cancer risk. Ann Oncol 16: 1211-1212.
• Rovio AT, Marchington DR, Donat S, Schuppe HC, Abel J, Fritsche E, Elliott DJ, Laippala P, Ahola AL, McNay D, Harrison RF, Hughes B, Barrett T, Bailey DM, Mehmet D, Jequier AM, Hargreave TB, Kao SH, Cummins JM, Barton DE, Cooke HJ, Wei YH, Wichmann L, Poulton J, Jacobs HT (2001) Mutations at the mitochondrial DNA polymerase (POLG) locus associated with male infertility. Nat Genet 29: 261-262.
• Singh KK, Ayyasamy V, Owens KM, Koul MS, Vujcic M (2009) Mutations in mitochondrial DNA polymerase-gamma promote breast tumorigenesis. J Hum Genet 54: 516-524.
• Spelbrink JN, Toivonen JM, Hakkaart GA, Kurkela JM, Cooper HM, Lehtinen SK, Lecrenier N, Back JW, Speijer D, Foury F, Jacobs HT (2000) In vivo functional analysis of the human mitochondrial DNA polymerase POLG expressed in cultured human cells. J Biol Chem 275: 24818-24828.
• Stumpf JD, Copeland WC (2011) Mitochondrial DNA replication and disease: insights from DNA polymerase gamma mutations. Cell Mol Life Sci 68: 219-233.
• Van Goethem G, Dermaut B, Löfgren A, Martin JJ, Van Broeckhoven C (2001) Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions. Nat Genet 28: 211-212.
• Velasco A, Riquelme E, Schultz M, Wistuba II, Villarroel L, Koh MS, Leach FS (2004) Microsatellite instability and loss of heterozygosity have distinct prognostic value for testicular germ cell tumor recurrence. Cancer Biol Ther 3: 1152-1158; discussion 1159-1161.

Identifiers

DOI

10.18388/abp.2014_935