Associations betweenXPC expression, genotype, and the risk of head and neck cancer

Abstract

Squamous cell carcinoma of the head and neck (SCCHN) is a relatively rare cancer with a poor prognosis. In the present study, we investigated susceptibility biomarkers for SCCHN in 155 Koreans (73 SCCHN cases and 82 controls). Expression of the xeroderma pigmentosum group C (XPC) DNA-repair gene was measured by TaqMan fluorogenic real-time RT-PCR using RNA isolated from peripheral blood samples. In addition, the XPC-PAT genotype [an intronic and biallelic poly(AT) insertion/deletion polymorphism] was determined by PCR of peripheral blood DNA. Among known environmental and physical risk factors, age, gender, tobacco smoking, and alcohol consumption were associated with the SCCHN risk (P < 0.01). Lower XPC expression levels were found for the SCCHN cases, particularly in the larynx, than for the controls (P < 0.05); the geometric means (standard deviations) of XPC expression normalized by 18S rRNA in the cases and controls were 5.89 (8.13) and 15.14 (9.77), respectively. However, the distributions of the XPC-PAT genotypes were similar in the cases and controls. In addition, there were no associations between the expression of XPC and the PAT genetic polymorphism. XPC expression was not affected by age, gender, tobacco smoking, or alcohol consumption. After adjusting for SCCHN-associated lifestyle factors, the effective strength of XPC expression on SCCHN risk was weaker (0.05 < P < 0.1) than those of tobacco smoking and age (P < 0.05). There was a positive association between XPC mRNA expression in blood and SCCHN tissues (n = 9; P < 0.01); therefore, peripheral blood appears to be a reasonable surrogate tissue for XPC expression in tumor tissue. In conclusion, the XPC-PAT polymorphism had no effect on XPC expression or SCCHN risk. However, XPC expression may influence SCCHN risk.

A meta-analysis of DNA repair gene XPC polymorphisms and cancer risk

“…Through literature search and selection based on the inclusion criteria, 32 articles (37 studies) were found, and 28 articles (Bai et al 2007;Blankenburg et al 2005;Casson et al 2005;De Ruyck et al 2007;Festa et al 2005;Hansen et al 2007;Hirata et al 2007;Hu et al 2005;Huang et al 2006;Kietthubthew et al 2006;Lee et al 2005;Li et al 2006;Marin et al 2004;Mechanic et al 2006;Nelson et al 2005;Sak et al 2005Sak et al , 2006Sanyal et al 2004;Shen et al 2001Shen et al , 2005Sugimura et al 2006;Vogel et al 2005;Wang et al 2006;Weiss et al 2005;Yang et al 2005;Ye et al 2006;Zhou et al 2006;Zhu et al 2007) (32 studies) met our inclusion criteria, as listed in Table 1. One study of A33512C (Hirata et al 2006) reported an extremely high variant allele frequency, which may result from wrong allele counting or poor genotyping quality, and was finally excluded from our meta-analysis.…”

“…Among the 28 eligible articles, 18 articles (Bai et al 2007;Blankenburg et al 2005;Festa et al 2005;Hansen et al 2007;Hirata et al 2007;Hu et al 2005;Huang et al 2006;Kietthubthew et al 2006;Lee et al 2005;Li et al 2006;Mechanic et al 2006;Sak et al 2005;Sanyal et al 2004;Vogel et al 2005;Weiss et al 2005;Ye et al 2006;Zhou et al 2006;Zhu et al 2007) (23 studies) described A33512C, ten articles (Bai et al 2007;Hu et al 2005;Huang et al 2006;Lee et al 2005;Li et al 2006;Sak et al 2006;Shen et al 2005;Weiss et al 2005;Zhou et al 2006;Zhu et al 2007) (11 studies) described C21151T, and 13 articles (Blankenburg et al 2005;Casson et al 2005;De Ruyck et al 2007;Kietthubthew et al 2006;Li et al 2006;Marin et al 2004;Nelson et al 2005;Sak et al 2005;Shen et al 2001;Sugimura et al 2006;Wang et al 2006;Yang et al 2005;Zhu et al 2007) (14 studies) described PAT -/+; 82.1% (23/28) stated that the age and gender status were matched between case and control popul...…”

Polymorphisms in DNA damage response genes and head and neck cancer risk

“…Several molecular epidemiologic studies have evaluated the association of head and neck cancer with polymorphisms in DNA repair genes, such as XPA (An et al, 2007, Bau et al, 2007, Hall et al, 2007, Sugimura et al, 2006, Abbasi et al, 2009), XPC (Kietthubthew et al, 2006, Shen et al, 2001, Sugimura et al, 2006, Wang et al, 2007, Yang et al, 2005), XPD (An et al, 2007, Bau et al, 2007, Harth et al, 2008, Huang et al, 2005, Kietthubthew et al, 2006, Majumder et al, 2007, Ramachandran et al, 2006, Sturgis et al, 2002a, Sturgis et al, 2002b, Sturgis et al, 2000, Rydzanicz et al, 2005, Gajecka et al, 2005b), XPF (Sugimura et al, 2006), ERCC1 (An et al, 2007, Sturgis et al, 2000, Sugimura et al, 2006), XRCC1 (Demokan et al, 2005, Harth et al, 2008, Kietthubthew et al, 2006, Kowalski et al, 2009, Majumder et al, 2005, Olshan et al, 2002, Ramachandran et al, 2006, Sturgis et al, 1999, Tae et al, 2004, Varzim et al, 2003, Yen et al, 2008, Rydzanicz et al, 2005, Gajecka et al, 2005b, Csejtei et al, 2009) and XRCC3 (Benhamou et al, 2004, Huang et al, 2005, Kietthubthew et al, 2006, Majumder et al, 2007, Werbrouck et al, 2008, Yen et al, 2008, Gajecka et al, 2005b, Rydzanicz et al, 2005). However, the results are conflicting rather than conclusive.…”

Head and Neck Squamous Cell Carcinoma: Prognosis using molecular approach

“…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].…”