Genetic polymorphisms in DNA base excision repair gene XRCC1 and the risk of squamous cell carcinoma of the head and neck

Abstract

Background: The genes of base excision repair (BER) pathway have been extensively studied in the association with various human cancers. We performed a case-control study to test the association between two common single nucleotide polymorphisms (SNPs) of XRCC1 gene with human head and neck squamous cell carcinoma (HNSCC).

Association between polymorphisms in genes related to DNA base-excision repair with risk and prognosis of oropharyngeal squamous cell carcinoma

“…To our knowledge, there are no previous studies on the function of c.-77T>C SNP on OPSCC or overall HNSCC risk. We also found no association of XRCC1 c.839G>A and c.1196G>A SNPs with OPSCC risk, according to previous results from overall HNSCC studies (Sturgis et al 1999;Tae et al 2004;Demokan et al 2005;Matullo et al 2006;Li et al 2007;Harth et al 2008;Applebaum et al 2009;Csejtei et al 2009;Kowalski et al 2009;Gugatschka et al 2011;Al-Hadyan et al 2012;Yuan et al 2012). In contrast, the variant allele A of c.1196G>A SNP was associated with decreased risk (Olshan et al 2002;Kumar et al 2012;Khlifi et al 2014) and increased risk (Choudhury et al 2014) of overall HNSCC.…”

“…The roles of the OGG1 c.977C>G (Elahi et al 2002;Zhang et al 2004;Matullo et al 2006;Görgens et al 2007;Hall et al 2007;Kumar et al 2011;Mitra et al 2011), APEX1 c.444T>G (Matullo et al 2006;Li et al 2007); XRCC1 c.-77T>C, c.580C>T (Sturgis et al 1999;Olshan et al 2002;Tae et al 2004;Demokan et al 2005;Matullo et al 2006;Applebaum et al 2009;Csejtei et al 2009;Kowalski et al 2009;Gugatschka et al 2011;Kumar et al 2012), c.839G>A (Tae et al 2004;Applebaum et al 2009;Gugatschka et al 2011;Kumar et al 2012) and c.1196G>A (Sturgis et al 1999;Olshan et al 2002;Tae et al 2004;Demokan et al 2005;Matullo et al 2006;Li et al 2007;Harth et al 2008;Applebaum et al 2009;Csejtei et al 2009;Kowalski et al 2009;Gugatschka et al 2011;AlHadyan et al 2012;Kumar et al 2012;Yuan et al 2012;Choudhury et al 2014;Khlifi et al 2014) SNPs in overall HNSCC risk are still controversial or unknown.…”

Head and Neck Squamous Cell Carcinoma: Prognosis using molecular approach

“…At the cellular and tissue level, these biological responses become modified by exogenous and endogenous compounds due to the occurrence of polymorphic alleles in DNA repair genes that alter the repair capacity, thereby developing different kinds of diseases, such as cancer [17]. The polymorphic DNA repair genes involved in HNSCC are grouped into four major DNA repair pathways: Base excision repair (BER), nucleotide excision repair (NER), double-strand DNA breaks repair (DSBR) and mismatch repair (MMR) [12][13][14].…”

“…The XRCC1 gene (X-ray repair cross complementing group 1) involved in the base excision repair pathway has been extensively studied in association with various human cancers [14]. XRCC1 is located on chromosome 19q13.2, which encodes a 633 amino acid protein and interacts with many components of the base excision DNA repair (BER) pathway, such as PARP-1(Poly-ADP ribose polymerase), PNK (Poly nucleotide kinase), Polβ (DNA polymerase β), LIG3 (Ligase 3α) etc.…”

“…Ironically, defects in these pathways have been implicated in causing excessive cell death or transformation of cells, resulting in increased risk of HNSCC [5,6]. Polymorphisms in DNA repair genes such as XPA (Xeroderma Pigmentosum Complementation group A) [7,8], XPC (Xeroderma Pigmentosum Complementation group C) [9,10], XPD (Xeroderma Pigmentosum Complementation group D) [11,12], XRCC1 (X-Ray Cross Complementing group 1) [13,14], XRCC3 (X-Ray Cross Complementing group 3) [15,16] and Phase II xenobiotic metabolizing genes such as Glutathione S-transferases (GSTs: M1, T1 and P1) have been reported in the pathophysiology of HNSCC [1,2,17]. Moreover, any catastrophic change in the p53 gene, along with poor diet and other occupational hazards, can bring about the occurrence of HNSCC [18].…”