Back to Search
Start Over
XRCC1 codon 399 mutant allele: a risk factor for recurrence of urothelial bladder carcinoma in patients on BCG immunotherapy.
- Source :
-
Cancer biology & therapy [Cancer Biol Ther] 2008 May; Vol. 7 (5), pp. 645-50. Date of Electronic Publication: 2008 May 20. - Publication Year :
- 2008
-
Abstract
- XRCC1 protein plays crucial role in base excision repair (BER)by acting as a scaffold for other BER enzymes. Variants in XRCC1 gene might alter protein structure/function or create alternatively spliced protein influencing BER efficiency and affect individual susceptibility/recurrence to urinary bladder cancer (BC). We tested whether polymorphisms in XRCC1 gene were associated with BC risk and further to substantiate risk of recurrence after Bacillus Calmette-Guerin (BCG) immunotherapy. Genotyping for three polymorphic sites of XRCC1 gene at codon Arg194Trp (PvuII), Arg280His (RsaI) and Arg399Gln (MspI) in 140 BC cases and 190 controls by PCR-RFLP method was done. We observed significant association in heterozygous genotype (GA) of codon 280 and 399 with BC risk (OR = 1.96, p = 0.021 and OR = 1.81, p = 0.021, respectively), however no association was seen for variant AA genotype. A trend of increased risk with high stage and grade in patients with codon 194 variant genotypes (CT + TT) was observed. Haplotype analysis showed that individuals with haplotype 194C-280G-399A were at >3-fold higher risk for BC (OR = 3.48, p = 0.01). The A/A genotype of codon 399 was associated with high risk for recurrence in BCG treated patients (HR = 5.05, p = 0.01) thus, showing reduced recurrence free survival (AA/GG = 12/60 months; log rank p = 0.004). The study suggested no association of variant genotypes with the susceptibility to BC. Haplotype analysis however, revealed that XRCC1 399 A allele may have a major role as patients with haplotype 194C-280G-399A carrying variant allele of 399 were at higher risk.
Details
- Language :
- English
- ISSN :
- 1555-8576
- Volume :
- 7
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Cancer biology & therapy
- Publication Type :
- Academic Journal
- Accession number :
- 18364571
- Full Text :
- https://doi.org/10.4161/cbt.7.5.5763