De Association of the polymorphism of the CAG repeat in the mitochondrial DNA polymerase gamma gene (POLG) with testicular germ-cell cancer.

Department of Growth and Reproduction, Rigshospitalet, Blegdamsvej, Copenhagen, Denmark.
Annals of Oncology (Impact Factor: 7.04). 11/2008; 19(11):1910-4. DOI: 10.1093/annonc/mdn407
Source: PubMed


A possible association between the polymorphic CAG repeat in the DNA polymerase gamma (POLG) gene and the risk of testicular germ-cell tumours (TGCT) was investigated in this study. The hypothesis was prompted by an earlier preliminary study proposing an association of the absence of the common 10-CAG-long POLG allele with testicular cancer as well as previously reported in some European populations' association with male subfertility, which is a condition carrying an increased risk of TGCT.
The number of CAG repeats in both POLG alleles was established in 243 patients with TGCT and in 869 controls by the analysis of the genomic DNA fragment.
A significantly higher proportion of men homozygous allele of other than the common 10 CAG repeats was found among the patients with TGCT in comparison to the controls (4.9% versus 1.3%, respectively, P = 0.001). The vast majority of the homozygous patients had a seminoma (11 of 12; 97%), despite that only about half (55%) of the studied patients had this tumour type.
The findings indicate that the POLG polymorphism may be a contributing factor in the pathogenesis of TGCT particularly in seminoma, but the mechanisms remain to be elucidated.

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Available from: Gedske Daugaard, Dec 29, 2013
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    • "The stretch of 13 glutamine residues encoded by 10 CAG codons localized near the N-terminus of the DNA polymerase is called POLG CAG trinucleotide repeat (Ropp & Copeland, 1996). These are associated to idiopathic sporadic Parkinson's disease (Luoma et al., 2007), testicular cancer (Blomberg Jensen et al., 2008) and male infertility (Jensen et al., 2004). Point mutation at position 8344 in the mtDNA produces an impaired function of the oxidative phosphorylation complex IV leading to development of lipomas and has been associated to multiple symmetrical lipomatosis (MSL) (Becker-Wegerich et al., 1998). "
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    • "The POLG gene contains a polymorphic CAG repeat of a dominant length of 10. Men with homozygous deviations from this length have an increased risk of developing seminomas[99]. The percentage of the homozygous non-10 allele is significantly higher in cancer patients than in the general population, yet is only present in low frequencies. "
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    • "Since the clearly dominating repeat length in the human population is 10, selective pressure seems to occur to conserve this length [73]. Men with homozygous deviations from this dominating repeat length were recently shown to have an increased risk of developing testicular germ cell cancer, mainly seminomas [74]. No correlation of repeat length with other clinico-pathological features was observed. "
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