Worldwide Distribution of Four SNPs in X‐Ray and Repair and Cross‐Complementing Group 1 (XRCC1)

Abstract

Purpose X‐ray repair cross‐complementing group 1 (XRCC1) repairs single‐strand breaks in DNA. Several reports have shown the association of single nucleotide polymorphisms (SNPs) (Arg194Trp, Pro206Pro, Arg280His, Arg399Gln) in XRCC1 to diseases. Limited population data are available regarding SNPs in XRCC1, especially in African populations. In this study, genotype distributions of four SNPs in worldwide populations were examined and compared with those reported previously. Materials and Methods Four SNPs (Arg194Trp, Pro206Pro, Arg280His, Arg399Gln) in XRCC1 from genomic DNA samples of 10 populations were evaluated by using polymerase chain reaction followed by restriction fragment length polymorphism analysis. Results The frequency of the minor allele corresponding to the Trp allele of XRCC1Arg194Trp was higher in Asian populations than in African and Caucasian populations. As for XRCC1Pro206Pro, Africans showed higher minor allele frequencies than did Asian populations, except for Tamils and Sinhalese. XRCC1 Arg280His frequencies were similar among Africans and Caucasians but differed among Asian populations. Similarly, lower mutant XRCC1 Arg399Gln frequencies were observed in Africans. Conclusions This study is the first to show the existence of a certain genetic heterogeneity in the worldwide distribution of four SNPs in XRCC1.

Association of XRCC1 Trp194 allele with risk of breast cancer, and Ki67 protein status in breast tumor tissues

“…African and Caucasian populations showed higher Arg allele frequencies. 13 In our study, the frequency of Trp allele was higher in patients group, this genotype had a great correlation with risk of breast cancer.…”

“…It has been found that the distribution of Arg194Trp polymorphism is significantly influenced by ethnicity. 13 The frequency of the Trp allele of XRCC1 Arg194Trp was higher in Asian populations than in African and Caucasian populations. African and Caucasian populations showed higher Arg allele frequencies.…”

“… 11 , 12 X-ray repair cross-complementing group 1 has been shown to have a large number of single-nucleotide polymorphisms (SNPs), several of which are being increasingly studied in cancer epidemiology investigations, in part because of their relative high frequency in the population. 13 Among them, Arg194Trp (rs1799782) has been shown to change the neoconservative amino acid, and thus result in alteration of DNA repair capacity. 14 The Arg194Trp polymorphism is located in the nuclear antigen-binding region.…”

“…Arg194Trp SNP, changes the ability of XRCC1 to interact with the other BER enzymes and consequently alter DNA repair capability. 9 , 10 , 13 The Trp194 variant has been associated with increased BER capacity, whereas the Arg194 allele has been related to significantly higher values of chromosomal breaks. Taken together a protective effect of the 194Trp allele may be suggested.…”

MTHFR, XRCC1 and OGG1 genetic polymorphisms in breast cancer: a case-control study in a population from North Sardinia

“…In our study no association with the risk of BC was demonstrated for XRCC1-rs1799782 (Arg to Trp) and rs25487 (Arg to Gln). The distribution of Arg194Trp and Arg399Gln polymorphisms are significantly influenced by ethnicity: the frequency of the Trp allele is higher in Asian populations than in African and Caucasian populations [66]. Furthermore, it has been observed that patients with the Arg/Arg genotype exhibited significantly higher levels of chromosomal breaks than those with the Trp allele [67].…”