Article

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: 6.58). 11/2008; 19(11):1910-4. DOI: 10.1093/annonc/mdn407
Source: PubMed

ABSTRACT 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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    • "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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Mitokondriaalista polymeraasi gamma-entsyymiä koodaavan POLG1 geenin eksonissa 2 olevasta polymorfisesta CAG-toistojaksosta löytyi todennäköinen PT:n riskitekijä. Tämä CAG-toisto koodaa polyglutamiiniketjua (polyQ), jonka yleisimmät pituudet ovat 10Q (86-90%) ja 11Q. Suomalaisilla potilailla polyQ-alleellit, jotka olivat lyhyempiä kuin 10Q tai pidempiä kuin 11Q (non-10/11Q) olivat yleisempiä kuin kontrolleilla (10 vs. 3.5 %, p= 0.003). Teimme replikaatiotutkimuksen pohjoisamerikkalaisessa aineistossa (652 PT-potilasta, 292 kontrollia). Non-10/11Q alleelit olivat potilailla yleisempiä kuin kontrolleilla, mutta ei merkittävästi (p=0.07). Monissa aiemmissa POLG1 polyQ:ta muissa ilmiasuissa tutkineissa töissä ainoastaan 10Q alleelia on pidetty normaalina alleelina. Non-10Q-alleelit olivat selvästi yleisempiä PT-potilailla kuin kontrolleilla (17.3% vs. 12.3 %, p= 0.005) tai 1541 kirjallisuuskontrollilla (p=0.00005). 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