Genetic Polymorphisms in XRCC1, APE1, ADPRT, XRCC2, and XRCC3 and Risk of Chronic Benzene Poisoning in a Chinese Occupational Population

Abstract

DNA damage induced by benzene is an important mechanism of its genotoxicity that leads to chronic benzene poisoning (CBP). Therefore, genetic variation in DNA repair genes may contribute to susceptibility to CBP in the exposed population. Because benzene-induced DNA damage includes single-and double-strand breaks, we hypothesized that single-nucleotide polymorphisms in X-ray repair crosscomplementing group 1 (XRCC1), apurinic/apyrimidinic endonuclease (APE1), ADP ribosyltransferase (ADPRT), X-ray repair cross-complementing group 2 (XRCC2), and X-ray repair cross-complementing group 3 (XRCC3) are associated with risk of CBP. We genotyped single-nucleotide polymorphisms at codons 194, 280, and 399 of XRCC1, codon 148 of APE1, codon 762 of ADPRT, codon 188 of XRCC2, and codon 241 of XRCC3 in 152 CBP patients and 152 healthy workers frequency matched on age and sex among those who were occupationally exposed to benzene. The genotypes were determined by PCR-RFLP technique with genomic DNA. We found that no individuals had the XRCC2 codon 188 variant alleles or Met/Met genotype of XRCC3 codon 241 in this study population. However, individuals carrying the XRCC1 194Trp allele (i.e., Arg/Trp+Trp/Trp genotypes) had a decreased risk of CBP [adjusted odds ratio (OR adj ), 0.60; 95% confidence interval (95% CI), 0.37-0.98; P = 0.041] compared with subjects with the Arg/Arg genotype whereas individuals carrying the XRCC1 280His allele (i.e., Arg/His+His/His genotypes) had an increased risk of CBP compared with those with the Arg/Arg genotype (OR adj , 1.91; 95% CI, 1.17-3.10; P = 0.009). The analysis of haplotypes of polymorphisms in XRCC1 showed that there was a 2.96-fold (OR, 2.96; 95% CI, 1.60-5.49; C 2 = 12.39, P = 0.001) increased risk of CBP for subjects with alleles of XRCC1 194Arg, XRCC1 280His, and XRCC1 399Arg compared with those carrying alleles of XRCC1 194Arg, XRCC1 280Arg, and XRCC1 399Arg. Therefore, our results suggest that polymorphisms at codons 194 and 280 of XRCC1 may contribute to CBP in a Chinese occupational population. (Cancer Epidemiol Biomarkers Prev 2005;14(11):2614 -9)

Polymorphisms in DNA repair genes XRCC2 and XRCC3 risk of gastric cancer in Turkey

“…In this study, we found that the frequency of the T allele was twofold higher in gastric cancer patients. Also, the G allele of the APE gene family was observed more frequently in patients with common digestive system cancer types [24,28]. In the present study, the frequency of the G allele was 0.78 and therefore high.…”

“…Linking variation in polymorphic sites of the XRCC2 and XRCC3 has been conducted for various cancer types [22][23][24]. It was found that the XRCC3 Th r241Met polymorphism was associated with the risk of breast cancer [25].…”

“…On the other hand, determined that there were polymorphic regions that were more frequently associated with melanoma skin cancer than cancer occurring in head, neck, bladder, and breast cancer. Th erefore, the eff ect of the XRCC3 gene varies in diff erent cancer types [31][32][33][34][35]. A recent study conducted in Poland focused on same genomic regions and cancer type, and has shown that the regions of interest are associated with cancer [19,20].…”

Polymorphism of DNA repair genes (XRCC1, XRCC3, XPD, XPC) and risk of uterine myoma among women working in petrochemical complex

“…Известно, что устойчивый метаболит бензола р-бензо-хинон, формирует р-бензохин-С аддукты, являющиеся субстратом для апуриновой/апиримидиновой эндо-нуклеазы (APE1). После вырезания таких аддуктов в зашивании бреши принимают участие ферменты экци-зионной репарации оснований XRCC1, ДНК-лигаза III, в том числе и XPС (Zhang, et al, 2005).…”

“…Ген ERCC2 (XPD), так же как и XPC, входит в группу NER-генов. Ген XPD ко-дирует геликазу, являющуюся частью транскрипци-онного фактора TFIIH, и, соответственно, изменения, затрагивающие функциональную активность XPD, изменяют способность к восстановлению структу-ры ДНК, что характеризуется повышением числа ДНК-аддуктов у лиц, носителей этого аллеля (Kiyohara et al, 2007 27), что объясняется имеющимися межэтническими различиями в распре-делении аллелей и генотипов по данному локусу между населением Европы и Азии и малочисленностью изу-чаемых выборок.…”