XRCC4 c.1394G>T Single Nucleotide Polymorphisms and Breast Cancer Risk among Filipinos

Abstract

Background:The identification of cancer-associated single nucleotide polymorphisms (SNP) and mutation genes is a promising approach in recognizing individuals who are at risk of developing cancer. Hence, this study was conducted to determine the association between XRCC4 c.1394G>T SNP and breast cancer development among Filipinos. Methods: Genotyping for XRCC4 c.1394G>T SNP was performed on breast cancer patients (n=103) and their age-and sex-matched clinically healthy controls (n=103) by polymerase chain reaction -restriction fragment length polymorphism. Results: Significant difference in genotype (p=0.007) and allele (p=0.003) frequencies in XRCC4 c.1394G>T was observed between the breast cancer cases and controls. Carriers of the XRCC4 c.1394 G>T genotype were observed to have significantly higher risk of developing breast cancer compared to individuals with T/T genotype (OR=2.67, 95% CI: 1. 36 -5.25). XRCC4 c.1394G>T combined with passive smoking may also significantly increase risk of breast cancer (OR=14.73; 95% CI= 9.88-18.86). Conclusion: XRCC4 c. 1394G>T may be associated with breast cancer development among Filipinos.

X-Ray Repair Cross Complementing 4 (XRCC4) Genetic Single Nucleotide Polymorphisms and the Liver Toxicity of AFB1 in Hepatocellular Carcinoma

“…This gene's encoding protein plays a vital role in both NHEJ and the completion of V(D)J recombination via acting as a scaffold protein for DNA ligase IV and DNA-PK in the repair of DNA DSBs [15,19]. Mutations in XRCC4, including GSNPs and other non-GSNPs variants, can cause endocrine dysfunction, microcephaly, short stature, and diseases [16,21]. With the development of human Geno projects, more than 1000 GSNPs are identified.…”

“…Among these GSNPs, we focused on genetic alterations in the coding regions of XRCC4, mainly because they will result in missense mutations and ultimately cause the structure damage and function deficiency of XRCC4 protein. Molecular epidemiological studies have displayed that the GSNPs in the XRCC4 genes can increase DNA repair capacity and increase the risk of some tumors such as lung cancer, colon cancer, HCC, and so on [21,[46][47][48][49][50][51]. Evidence from in vitro and in vivo studies has also proved that XRCC4 GSNPs increase the amount of DNA damage and induce more gene mutations [23,24,26,27].…”

“…X-ray repair cross complementing 4 (XRCC4), an important DNA repair gene involved in nonhomologous end-joining (NHEJ) repair pathway, plays a scaffold function via stabilizing and localizing DNA repair enzymes LIG IV, Ku70/80 heterodimer, and the DNA-dependent protein kinase (DNA-PK) catalytic subunit (DNA-PKcs) in the ends of DNA double-stranded breaks (DSBs) during NHEJ [15,16]. In the past decades, growing reports have exhibited that the abnormal structures and functions of XRCC4 may alter the capacity of DNA repair and ultimately result in human diseases [17][18][19][20][21][22]. Several recent studies have also shown that the genetic alterations in the coding regions of XRCC4 can modify hepatocellular carcinoma (HCC) risk and prognosis [23][24][25][26][27].…”

Genetic profile for the detection of susceptibility to poisoning by exposure to pesticides

“…Other affected pathways are the repair of oxidative damage to guanine (8-oxoguanine) by the OGG1 (8-Oxoguanine DNA Glycosylase) gene [4,10,15]; and the non-homologous end-joint mechanism (NHEJ) that is responsible for the repair of double-stranded DNA breaks, by XRCC4 (X-Ray Repair Cross-Complementing Group 4) repair gene. The basic mechanism involved in each repair pathway is shown in Figure 1 [16][17][18].…”

“…It encodes a phosphoprotein called X-Ray Repair Cross-complementing Group 4 that contains 336 amino acids and three constituent domains [17,27,28]. This protein plays a major role in the NHEJ mechanism, which is necessary for the repair of double-stranded DNA breaks [16,29,30]. This process involves interaction with ligase 4 (Lig4) and factor XLF (XRCC4-factor, also known as Cernunnos or NHEJ1), thus facilitating ligation of the non-core and complementary ends of DNA [16,28,30].…”