[Correlation between XRCC2 and XRCC5 single nucleotide polymorphisms and drug-sensitivity of human lung cancer cells].
OBJECTIVE
To study the associations between XRCC2 and XRCC5 single nucleotide polymorphisms (SNPs) and chemosensitivity of human lung cancer cells.


METHODS
Specimens of human lung cancer were collected from 150 patients, 120 males and 30 females, aged 58.1, during operation. MTT method was used to detect the sensitivity of the lung cancer cells to cisplatin (DDP) and carboplatin (CBP), and the patients were genotyped for polymorphisms in XRCC2 and XRCC5 genes. The polymorphisms of XRCC2 41657T C41657T and XRCC5 G74582A were detected by polymerase chain reaction-restriction fraction length polymorphism (PCR-RFLP), and the polymorphisms of XRCC2 G4234C and XRCC5 C74468A were detected by primer-introduced restriction analysis- polymerase chain reaction (PIRA-PCR). The correlation of these polymorphisms of these polymorphisms with the drug-sensitivity of lung cancer cells was analyzed.


RESULTS
The sensitive rates of the lung cancer cells to CBP and DDP in the patients with XRCC2 41657T allele (C/T + T/T genotype) were 70.2% and 66.7% respectively, both significantly higher the those in the patients with C/C genotype [53.7% (chi(2) = 3.97, P = 0.046) and 49.5% (chi(2) = 4.25, P = 0.039) respectively]. The sensitivity levels to CBP and DDP in the patients with at least one T allele was 2.06 times (pathological type adjusted OR = 2.06, 95% CI = 1.02 - 4.18) and 2.07 times (pathological type adjusted OR = 2.07, 95% CI = 1.04 - 4.14) higher than those in the patients with C/C genotype. There was no significant difference in the distribution of genotypes of XRCC2 G4234C C allele (C/C + G/C) and G/C genotype between the sensitive group and resistant groups (chi(2) = 0.09, P = 0.766 for CBP and chi(2) = 1.63, P = 0.202 for DDP). The sensitivity rate to DDP of the patients with 41657T/4234G haplotype was 2.28 times as high as that of the patients with 41657T/4234C (OR = 2.18, 95% CI = 1.15 - 4.12). The sensitivity rates to CBP and DDP of the tumor tissues from the patients with the XRCC5 G74582A G allele (A/G + G/G), were 57.9% and 61.8% respectively, and those of the patients with the A/A genotype were 62.2% and 50.0% respectively. There was no significant differences in the genotype distribution between the sensitive and resistant groups (chi(2) = 0.28, P = 0.594 for CBP, and chi(2) = 2.13, P = 0.144 for and DDP).


CONCLUSIONS
The XRCC2 C41657T SNP is associated with the sensitivity to CBP and DDP. The sensitive rate to the drugs of the cancer cells with the combination of C/T + T/T genotype is higher than that with C/C genotype. In the subject with 41657T/4234G the sensitivity to the drugs of the cancer cells is higher than that with 41657C/4234G haplotypes. The XRCC5 G74582A and C74468A SNPs are not associated with the sensitivity to CBP and DDP.
Wang
Rui
R
Department of Thoracic Surgery, Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang 050011, China. xwkwr@yahoo.com.cn
Wang
Wei
W
Zhang
Jin-Wen
JW
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D016190:Carboplatin / Q000494:pharmacology; D004265:DNA Helicases / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D000072200:Ku Autoantigen; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
D004268:DNA-Binding Proteins; C113187:XRCC2 protein, human; D016190:Carboplatin; D004265:DNA Helicases; C106893:XRCC5 protein, human; D000072200:Ku Autoantigen