Association of XRCC1 gene polymorphisms with the susceptibility and chromosomal aberration of testicular germ cell tumors.
It is known that many genomic and genetic alterations caused by aging or environmental factors are responsible for cancer development and progression. XRCC1 is involved in the repair of DNA single-strand breaks formed by exposure to ionizing radiation and alkylating agents. The objective of this study was to investigate the association of genomic alterations and the susceptibility of testicular germ cell tumors with XRCC1 polymorphisms. Two polymorphisms of XRCC1, Arg194Trp and Arg399Gln, were genotyped in 83 patients with testicular germ cell tumors (TGCT) and 87 male controls. Allelic imbalances (AI) were evaluated using 4 microsatellite markers in a subgroup of 50 patients. Patients with at least one Gln allele of the Arg399Gln polymorphism had an increased risk of TGCT than those with the Arg/Arg genotype (aOR=1.775, 95% CI=1.045-3.016, P=0.034). Furthermore, the increased risk associated with the Gln allele against the Arg homozygote was more strongly observed in patients with pure seminoma (aOR=2.242, 95% CI=1.149-4.374, P=0.018) or with metastasis (aOR=2.481, 95% CI=1.267-4.862, P=0.008). In the Arg194Trp polymorphism, there was no significant difference in the genotype distribution between TGCT patients and the controls. In AI analysis, the frequency of AI was significantly higher in tumors with at least one Gln allele than those with the Arg/Arg genotype in D13S317 (P=0.010) and in a combination of 4 markers (0.51+/-0.32 vs 0.32+/-28, P=0.028). Our results suggest that the Gln allele of the XRCC1 Arg399Gln polymorphism may genetically modify the development and progression of TGCT through genomic instability.
Tsuchiya
Norihiko
N
Department of Urology, Akita University School of Medicine, Hondo, Akita 010-8543, Japan.
Mishina
Mutsuki
M
Narita
Shintaro
S
Kumazawa
Teruaki
T
Inoue
Takamitsu
T
Horikawa
Yohei
Y
Kakinuma
Hideaki
H
Yuasa
Takeshi
T
Matsuura
Shinobu
S
Satoh
Shigeru
S
Ogawa
Osamu
O
Habuchi
Tomonori
T
D002869:Chromosome Aberrations; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012016:Reference Values; D013736:Testicular Neoplasms / Q000235:genetics* / Q000473:pathology; D000076105:X-ray Repair Cross Complementing Protein 1
D017931:DNA Primers; D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human