Genetic Variations in XRCC1 Gene in Sporadic Head and Neck Cancer (HNC) Patients

Abstract

DNA repair gene polymorphisms have been implicated as susceptibility factors in cancer development. It is possible that DNA repair polymorphisms may also influence the risk of gene mutation. Polymorphisms in the DNA repair gene XRCC1 have been indicated to have a contributive role in DNA adduct formation and an increased risk of cancer development. 300 head and neck cancer patients and 150 controls were included in this study. PCR-single-strand conformation polymorphism and DNA sequencing were used to analyze the whole exonic region of XRCC1 in head and neck cancer patients. Sequence analysis revealed two missense and two silent mutations in our study. Frequency of silent mutations; Pro206Pro (rs915927) and Gln632Gln (rs3547) was calculated as 0.16 (16 %) and 0.30 (30 %) respectively. Whereas, the frequency of missense mutations; Arg399Gln (rs25487) and Tyr576Asn (rs2307177) was calculated as 0.27 (27 %) and 0.28 (28 %) respectively. In our study, incidence of these mutations was found higher in larynx cancer (p < 0.005) as compared to oral cavity and pharynx cancer. Our finding suggests that the polymorphic XRCC1 gene may contribute to risk of developing head and neck cancer. To our knowledge, this is the first report that XRCC1 is associated with increased risk of head and neck cancer in a Pakistani population.

DNA Repair GenesXRCC1andERCC1Polymorphisms and the Risk of Sporadic Breast Cancer in Han Women in the Gansu Province of China

“…The Arg399Gln (rs25487) polymorphism has been studied in several epidemiological studies in relation to various cancers. It has been recently reported that the variant allele of XRCC1 rs25487 was significantly associated with an increased risk of glioma (Zhou et al, 2011), head, neck (Azad et al, 2012Mahjabeen et al, 2013), pancreatic (Nakao et al, 2012), and cervical carcinoma (Roszak et al, 2011), and breast cancer Roberts et al, 2011). These findings are consistent with our study among Chinese women in the Gansu province.…”

“…A reduced DNA repair capacity could lead to a predisposition to accumulated DNA damage, mutations, and subsequently developing diseases such as cancer (Rowe and Glazer, 2010). Polymorphisms in XRCC1 have been indicated to have a contributive role in DNA adduct formation and an increased risk of cancer development (Mahjabeen et al, 2013). The Arg399Gln (rs25487) polymorphism has been studied in several epidemiological studies in relation to various cancers.…”

Association of SYK Genetic Variations with Breast Cancer Pathogenesis

“…DNA was extracted from white blood cells, using standard phenol-chloroform extraction method (Mahjabeen et al, 2012) and stored at -20°C for further processing. Human SYK exon sequence was taken from Ensembl.…”

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

“…10,11 Several reports have shown the association of SNPs ( Arg194Trp , Pro206Pro , Arg280His , Arg399Gln ) in XRCC1 to diseases. [12][13][14][15][16][17][18][19][20] As described above, DNA repair capacity is infl uenced by SNPs in BER genes, and several studies have showed the association of XRCC1 polymorphisms to diseases. Data accumulation of SNPs in XRCC1 genes is important for elucidating the interindividual differences in capacity for repairing oxidative damage and susceptibility to disease.…”