Genetic polymorphisms in key DNA repair genes and risk of head and neck cancer in a Chinese population

Abstract

Abstract. Although tobacco and alcohol consumption are the major risk factors of head and neck cancer (HNC), genetic variations of genes involved in several biological pathways, such as DNA repair genes, may affect an individual's susceptibility to HNC. However, few studies have investigated the associations between polymorphisms in DNA repair genes and HNC risk in the Chinese population. Thus, we genotyped five common, non-synonymous single-nucleotide polymorphisms (SNPs) [APEX1 (Asp148Glu), XRCC1 (Arg399Gln), ADPRT (Val762Ala), XPD (Lys751Gln) and XPG (His1104Asp)] in a hospital-based, case-control study of 397 HNC cases and 900 cancer-free controls in China. The results showed that none of the five SNPs in the DNA repair pathway was significantly associated with HNC risk, suggesting that these polymorphisms may not play a major role in HNC susceptibility in this Chinese population. IntroductionThe incidence of head and neck cancer (HNC), especially squamous cell carcinoma of the head and neck (SCCHN), has markedly increased in the past 20 years and is now the fifth most common type of cancer worldwide (1). In the United States, it is estimated that there were 48,010 new cases and 11,260 deaths from SCCHN in 2010 (2). Accumulative evidence indicates that exposure to smoking and alcohol consumption are important risk factors of HNC (3); however, only few smokers and drinkers develop HNC, suggesting an individual susceptibility to this cancer in the general population. Most association studies on cancer susceptibility have focused on identifying effects of single-nucleotide polymorphisms (SNPs) in candidate genes of several pathways. Among these, genes involved in the DNA repair pathway are the most investigated due to their vital role in protecting the genome from insults of environmental carcinogens (4,5). Studies have shown inter-individual variations of DNA repair capacity (DRC) in the general population and the effect of a suboptimal DRC on the risk of smoking-related cancers, such as lung cancer and SCCHN (6-8).Of DNA repair pathways, nucleotide excision repair (NER) is the major repair mechanism for the DNA damage caused by tobacco smoking, which deals with a wide class of DNA damages, including bulky adducts cross-links, oxidative DNA damage, thymidine dimers and alkylating damage (9). NER involves more than 20 proteins whose inactivation may lead to xeroderma pigmentosum (XP) or Cockayne syndrome (CS). For example, rare mutations in xeroderma pigmentosum complementation group D and G (XPD and XPG) give rise to a combined XP/CS phenotype and are associated with severe neurological abnormalities.The base excision repair (BER) pathway is another important mechanism that repairs DNA damage resulting from chemical alterations of a single base; a number of proteins are involved in repair steps, such as apurinic/apyrimidinic endonuclease (APE1, also known as APEX1), X-ray repair crosscomplementing 1 (XRCC1) and ADP-ribosyltransferase (ADPRT, also known as PARP1) (10). APE1 is a key member in short-patch BER, w...

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.…”

Association Between the XRCC1 Arg399Gln Polymorphism and Head and Neck Cancer Susceptibility: A Meta-Analysis Based on Case–Control Studies

“…1; according to the inclusion criteria, a total of 29 studies with full-text articles that examined the association of the XRCC1 Arg399Gln with HNC susceptibility were found (Sturgis et al, 1999;Olshan et al, 2002;Varzim et al, 2003;Tae et al, 2004;Demokan et al, 2005;Gajecka et al, 2005;Huang et al, 2005;Rydzanicz et al, 2005;Kietthubthew et al, 2006;Matullo et al, 2006;Ramachandran et al, 2006;Ho et al, 2007;Li et al, 2007;Majumder et al, 2007;Harth et al, 2008;Yang et al, 2008;Applebaum et al, 2009;Csejtei et al, 2009;Kowalski et al, 2009;Jelonek et al, 2010;Gugatschka et al, 2011;Krupa et al, 2011;Al-Hadyan et al, 2012;Kumar et al, 2012aKumar et al, , 2012bYuan et al, 2012;Dos Reis et al, 2013;Khlifi et al, 2013;Kostrzewska-Poczekaj et al, 2013). Among them, two articles (Kumar et al, 2012a(Kumar et al, , 2012b were published using the same case series; the larger sample size (Kumar et al, 2012a) was included.…”

Head and Neck Squamous Cell Carcinoma: Prognosis using molecular approach

“…Furthermore, there is no significant risk of HNSCC for XRCC1 Arg 399 Gln genotypes among non-Hispanic white populations in the USA [26], the Hungarian population [27], or Polish population [28]. Recently, a meta analysis done by Flores-Obando et al [25] [33]. Khlifi R et al, (2013) reported that only the XRCC1 Arg 399 Gln polymorphism was associated with the risk of HNC in the Tunisian population (OR = 2.04; P = 0.001) [34].…”

“…Reports of XRCC1 polymorphism associated with HNSCC have been published across the globe. Yuan et al [25] conducted a case-control study for a total of 397 HNSCC patients and 900 cancer free controls among the Chinese population and reported that XRCC1 exon 10 codon (Arg 399 Gln) was not significantly associated with HNSCC risk (OR=0.93, 95% CI=0.76-1.13) [25]. Furthermore, there is no significant risk of HNSCC for XRCC1 Arg 399 Gln genotypes among non-Hispanic white populations in the USA [26], the Hungarian population [27], or Polish population [28].…”