POLYMORPHISM OF EXCISION REPAIR GENES XPD, XRCC1, hOGG1 IN THE POPULATION OF THE REPUBLIC OF BELARUS AND ITS IMPACT ON CARCINOGENESIS

Abstract

Background. DNA damage and induced mutational events are known to contribute notably to carcinogenesis, so the study of excision repair gene polymorphisms and their association with cancer risk is of great interest and importance. Materials and Methods. Excision repair gene polymorphisms (XRCC1 Arg399Gln, hOGG1 Ser326Cys, XPD Asp312Asn) were analyzed using a PCR-RFLP method in the group of bladder cancer (BC) patients compared to clinically healthy individuals. Results. In the healthy population, the frequencies of the minor alleles of XPD 312, XRCC1 399, hOGG1 326 genes were 42,1 %, 35,4 % and 24,4 %, respectively, i. e., in the range of values observed in Caucasian populations. The frequencies of genotypes/alleles in the group of BC patients did not differ from those in the control group. However, the frequency of Asn allele of XPD gene was significantly higher in men with BC recurrences as compared to primary tumors. The cancer risk was decreased in carriers of combined Asp/Asp, Arg/Arg, Ser/Ser genotypes of XPD, XRCC1 and hOGG1 genes (OR95 %CI = 0,46 [0,23 - 0,91] p = 0,024 and OR95 %CI = 0,42 [0,18 - 0,98] p = 0,045 for combination of two and three genes, respectively). Conclusion. In Belarus, the frequencies of the XPD, XRCC1 and hOGG1 minor alleles are similar to those in Caucasian populations. Although single nucleotide polymorphisms investigated did not affect the risk of bladder cancer, the risk of cancer recurrence was increased in carriers of the XPD Asn allele. Combined homozygous wild type alleles of indicated excision repair genes appeared to possess a protective effect against carcinogenesis.

The Cellular Response to Oxidatively Induced DNA Damage and Polymorphism of Some DNA Repair Genes Associated with Clinicopathological Features of Bladder Cancer

“…On the other hand, the random selection of sizeable populations, which are matched by the recruitment period, age and ethnicity, allows a higher frequency of smokers among BC patients to be considered as a disease-specific feature in support of findings that bladder cancer is an age-, gender-, and smoking-related disease [ 33 , 34 ]. It should also be mentioned that the percentage of smokers in the control population reflects the situation with tobacco consumption in Belarus, and the gene-smoking relationship in bladder cancer has been previously characterized [ 21 , 35 ]. A close association of bladder cancer with age and a tobacco smoking habit suggests that oxidative stress contributes to its development.…”

“…Combinations of the homozygous wild type alleles are expected to exert a reverse effect. Indeed, the combined wild type homozygotes for some DNA repair genes reduced susceptibility to bladder cancer [ 35 ] and even prevented tumor expansion ( Figure 4(b) ).…”

“…The impact of excision repair gene polymorphisms on susceptibility to different cancers, including urothelial carcinoma, has been widely discussed in literature [ 21 , 35 ]. Their associations with clinicopathological parameters of tumors are still poorly understood, although there are intriguing findings indicating the dual effects of DNA repair gene polymorphisms with respect to bladder cancer risk/recurrences/progression and clinical outcomes.…”