Correlation Of DNA Double Strand Break Repair Gene XRCC2 Polymorphisms To The Risk Of Ovarian Cancer

Objective: Ovarian cancer is frequency in gynecological tumour. Because we haven't systematical diagnose method in the early and effective treatment in the late so far, ovarian cancer become the main illness to threaten women's health and life. The prognosis of ovarian cancer is not very clear now, but genetic and environmental factor play an important part in it. DNA repair systems are essential for repairing DNA damage and maintaining genetic integrity to impress the occurance of tumours. There are many DNA repair pathways, DNA double strand break Repair is the main and most important repair pathway. The XRCC2 gene is an important component in DNA double strand break repair. XRCC2 gene have high incidence of polymorphism. Polymorphism in DNA repair gene may cause the diverse DNA repair capacity and influence an individual′s susceptibility to carcinogenesis.At present, the associations between XRCC2 polymorphisms and tumour risk have been extensively reported in our contury and abroad, however, few studies have focused on the role of the polymorphisms in XRCC2 for patients suffering ovarian cancer.This study was designed to investigate the correlation of single nucleotide polymorphisms (SNPs), C41657T and G4234C of XRCC2 gene, to susceptibilities of Ovarian cancer.Methods:1 220 patients with epithelial ovarian cancer were recruited from the gynecology and obstetrics department of the Fourth Affiliated Hospital of Hebei Medical University from December 2001 to October 2006. All the epithelial ovarian cancer patients were histologically confirmed. Ovarian cancer staging was performed by FIGO clinical standard. 244 healthy volunteers who had no clinical evidence of ovarian cancer or any other malignant tumours were randomly selected from Chinese blood donors as control subjects. All cases and controls were from Chinese Han population. The informed consent was got from all the recruited subjects. Five ml of venous blood from each subjecr was drawn in Vacutainer tubes containing EDTA and stored at 4℃. The genomic DNA was extracted within one week after bleeding by using proteinase K digestion followed by a salting out procedure. Polymorphisms of the XRCC2 gene were analyzed by PCR-restriction fragment length polymorphism analysis (RFLP).2 Statistical analyse was performed using the SPSS11.5 software package. P<0.05 was considered significant for all statistical analyses. Hardy-Weinberg analysis was performed by comparing the observed and expected genotype frequencies in study groups using Chi-square test. Comparison of the XRCC2 genotype, allelotype and haplotype distribution in cancer patients and healthy controls was performed by means of two-sided contingency tables using Chi-square test. The XRCC2 haplotype frequencies and linkage disequilibrium coefficient were estimated by using EH linkage software and 2LD software. The odds ratio (OR) and 95% confidence interval (CI) were calculated using an unconditional logistic regression model and adjusted by age.Results:1 The general information in ovarian cancer patients was comparable to the healthy controls. Samples from 220 patients and 244 control subjects were successfully genotyped for the XRCC2 C41657T and G4234C genotyping.2 The distribution of XRCC2 C41657T SNP and G4234C SNP genotypes among healthy controls did not significantly deviate from the expected Hardy-Weinberg equilibrium(P>0.05).3 The XRCC2C41657T allele frequency in ovarian cancer patients and healthy controls were 80.0%, 19.1% and 0.9%, 81.6%, 18.0% and 0.4%, respectively. There was no statistical difference between the two groups (P>0.05). For XRCC2C41657T polymorphism, the C and T allele frequency in ovarian cancer patients and healthy controls were 89.55%, 10.45% and 90.57%, 9.43%, respectively. There was no statistical difference in allele distribution between ovarian cancer patients and controls. Due to the low frequencies of T/T genotype, we combined C/Tand T/T genotype,contrast with C/C, C/T and T/T genotype can not increase the risk of developing ovarian cancer,there was no statistical difference between the two groups (P>0.05).The XRCC2 G4234C G/G,G/C and C/C allele frequency in ovarian cancer patients and healthy controls were 73.2%, 25.0% and 1.8%, 74.6%, 23.0% and 2.4%, respectively. There was no statistical difference between the two groups (P>0.05). For XRCC2 G4234C polymorphism, the G and C allele frequency in ovarian cancer patients and healthy controls were 85.68%, 14.32% and 86.07%, 13.93%, respectively. There was no statistical difference in allele distribution between ovarian cancer patients and controls Due to the low frequencies of C/C genotype, we combined C/Gand C/C genotype,contrast with G/G, G/C and C/C genotype can not increase the risk of developing ovarian cancer there was no statistical difference between the two groups (P>0.05).4 When the epithelial ovarian cancer patients were grouped according to the pathological characteristics, No significant difference was observed between the patients with the four pathological characteristics and the control group both for XRCC2 C41657T and G4234C (P>0.05). There was not statistical difference in the allele distribution of XRCC2 C41657T and G4234C between the cases and controls (P>0.05).5 When the epithelial ovarian cancer patients were divided into two groups according to the FIGO standard, there wasn't statistical difference between the early group and the late group for XRCC2 C41657T and G4234C (P>0.05).6 The combined effect of XRCC2C41657T and G4234C SNPs was analyzed by EH and 2LD software. It was shown that the two SNPs were in linkage disequilibrium (D'=0.522333,χ2=200.18, P=0.00). The haplotype distribution in ovarian cancer patients was not clearly different from that in healthy controls.Conclusions:1 XRCC2 C41657T and G4234C and polymorphism may not play a role in the genetic susceptibility to the development of ovarian cancer.2 By pathologic type, XRCC2 C41657T and G4234C gene and allele polymorphism may have not significant difference with ovarian cancer patients and controls.3 By FIGO, XRCC2 C41657T and G4234C may have no significant difference in ovarien cancer.4 The XRCC2 C41657T and G4234C SNPs were in linkage disequilibrium. The haplotype distribution had no influence on the risk of ovarien.