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Cancer Genet Cytogenet. 2010 Jan 1;196(1):31-7. doi: 10.1016/j.cancergencyto.2009.08.008.

DNA repair gene XRCC1 polymorphisms and haplotypes in diffuse large B-cell lymphoma in a Korean population.

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1
Department of Laboratory Medicine, Gyeongsang National University Hospital, 90 Chilam-dong, Jinju, 660-702, South Korea.

Abstract

DNA repair gene XRCC1 polymorphisms could lead to defective DNA repair and increased risk of lymphoma. This study was performed to evaluate the effect of polymorphisms and haplotypes of the XRCC1 gene on the risk of diffuse large B-cell lymphoma (DLBCL) and treatment outcomes after rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone (R-CHOP) chemotherapy in a Korean population. Carriers of XRCC1 194 variant genotypes had a significantly increased risk of DLBCL [adjusted odds ratio (OR), 1.57; 95% confidence interval (95% CI), 1.06-2.32; P = 0.028] among three polymorphisms of XRCC1 Arg194Trp, Arg280His, and Arg399Gln in 145 patients with DLBCL and in 515 healthy controls. Three polymorphisms of XRCC1 showed very strong linkage disequilibrium (LD) and consisted of one haploblock. The frequency of XRCC1 haplotype A (194Arg-280Arg-399Arg) was significantly lower in DLBCL patients compared to controls (OR, 0.60; 95% CI, 0.15-0.81; P = 0.001). The frequency of XRCC1 haplotype B (194Arg-280Arg-399Gln) was significantly higher in DLBCL patients compared to controls (OR, 1.38; 95% CI, 1.05-1.80; P = 0.019). The association between haplotype A and decreased risk of DLBCL was stable on permutation testing (P = 0.038). However, no relation was noted between these variant genotypes and treatment outcomes in DLBCL patients treated with R-CHOP chemotherapy. These findings suggest that haplotype A of XRCC1 plays a protective role against development of this disease and the haplotype estimation is advantageous for association studies of various cancers showing strong LD.

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