The X-ray Repair Cross-Complementing group 1 (XRCC1) protein, encoded by the XRCC1 gene, is essential in the base excision repair (BER) and single-strand break repair processes (SSBR). XRCC1 has been shown to physically interact with several enzymes known to be involved in the scaffolding protein complex, including DNA polymerase beta, PARP (ADP-ribose polymerase) and DNA ligase III in a complex, to facilitate the processes of base excision repair (BER) or single-strand break repair (SSBR). The XRCC1 protein might be independently involved in DNA damage recognition, since it can bind directly to both gapped and nicked DNA, as well as to gapped DNA associated with DNA polymerase beta.
Polymorphisms in the XRCC1 gene have been associated with either increased or decreased cancer susceptibility, depending on the type of cancer and the levels of environmental exposure to DNA damaging agents.
The XRCC1 gene is located on chromosome 19q13.2-13.3 and spans a genetic distance of 37.4 kb. The gene comprises of 17 coding exons and encodes a 70-kDa protein, consisting of 633 amino acids.
More than 300 single nucleotide polymorphisms (SNPs) in the XRCC1 gene have been reported; three of them are the most studied and lead to amino acid substitutions. These are p.Arg194Trp, p.Arg280His and p.Arg399Gln. The p.Arg399Gln has been associated with head and neck, colorectal, gastric, esophageal, breast, and lung cancers. The p.Arg194Trp polymorphism has been related to colorectal, gastric, head and neck, and skin cancers.
[See: Morocco > Laantri et al., 2011].
Laantri et al. (2011) analyzed three single nucleotide polymorphisms (SNPs) in the XRCC1 gene in 598 nasopharyngeal carcinoma (NPC) cases from Morocco, Algeria, and Tunisia and 545 controls frequency matched by recruitment center, age, sex, and urban/rural household. The genotype and allelic distributions for the XRCC1 p.Arg399Gln, p.Arg280His, and p.Arg194Trp SNPs did not differ significantly among NPC cases and controls. The XRCC1 p.Arg194Trp allele frequency was significantly lower in the North African population than in Asian population (f = 0.04 vs. 0.31 in Cantonese Chinese and 0.21 Han Chinese). Laantri et al. (2011) concluded that the XRCC1 gene is unlikely to play a role in the susceptibility to NPC in North Africans.
Alsbeih et al. (2008) studied the association between two SNPs, XRCC1 p.Arg399Gln and XRCC3 p.Thr241Met and late reactions to radiotherapy in 50 head and neck cancer Saudi patients. There were 43 males and seven females, with a median of 49 years. The appearance and the intensification of subcutaneous and deep tissues fibrosis were measured in the patients following radiotherapy. Using direct sequencing, allelic frequency showed significant association between XRCC1 p.Arg399Gln and risk of late normal tissue complication following radiotherapy. The XRCC3 p.Thr241Met SNP did not show such a significant association, although there was a trend towards it.