XPC polymorphisms play a role in tissue-specific carcinogenesis: a meta-analysis

Abstract

XPC participates in the initial recognition of DNA damage during the DNA nucleotide excision repair process in global genomic repair. Polymorphisms in XPC gene have been analyzed in case-control studies to assess the cancer risk attributed to these variants, but results are conflicting. To clarify the impact of XPC polymorphisms in cancer risk, we performed a meta-analysis that included 33 published case-control studies. Polymorphisms analyzed were Lys939Gln and Ala499Val. The overall summary odds ratio (OR) for the associations of the 939Gln/Gln genotype with risk of cancer was 1.01 (95% confidence interval (95% CI): 0.94 -1.09), but there were statistically significant associations for lung cancer, observed for the recessive genetic model (Lys/Lys þ Lys/Gln vs Gln/Gln), (OR 1.30; 95% CI: 1.113 -1.53), whereas for breast cancer a reduced but nonsignificant risk was observed for the same model (OR 0.87; 95% CI: 0.74 -1.01). The results for Ala499Val showed a significant overall increase in cancer risk (OR 1.15; 95% CI: 1.02 -1.31), and for bladder cancer in both the simple genetic model (Ala/Ala vs Val/Val) (OR 1.30; 95% CI: 1.04-1.61) and the recessive genetic model (Ala/Ala þ Ala/Val vs Val/Val) (OR 1.32; 95% CI: 1.06-1.63). Our metaanalysis supports that polymorphisms in XPC may represent low-penetrance susceptibility gene variants for breast, bladder, head and neck, and lung cancer. XPC is a good candidate for large-scale epidemiological case-control studies that may lead to improvement in the management of highly prevalent cancers.

Association between p53 Gene Variants and Oral Cancer Susceptibility in Population from Gujarat, West India

“…An allele frequency of Arg72Pro polymorphism has been reported to vary with respect to ethnicity and latitude (Nagpal et al, 2002). The allele frequency of proline at codon 72 varies from 0.12-0.69 worldwide (Francisco et al, 2011) whereas for the Indian population; it ranges from 0.42-0.72 (Nagpal et al, 2002;Tandle et al, 2001;Mitra et al, 2003;Mittal et al, 2011;Suresh et al, 2011). In our population, the frequency of proline was 0.46.…”

“…Studies from other populations showed conflicting results for the association of Arg72Pro polymorphism with oral cancer risk (Kietthubthew et al, 2003;Kuroda et al, 2007;Saini et al, 2011). Francisco et al (2011) suggested that ethnicity, allelic frequency, histological and anatomical sites may modulate the penetrance of Arg72Pro in cancer susceptibility. The results of intron 3 and intron 6 polymorphisms are also inconsistent and ranges from no association to increased risk in different population (Wang-Gohrke et al, 1999;Wu et al, 2002;Sprague et al, 2007;Gallì et al, 2009;Hrstka et al, 2009;Hu et al, 2010).…”

DNA Repair Capacity-Related to Genetic Polymorphisms of DNA Repair Genes and Aflatoxin B1-Related Hepatocellular Carcinoma Among Chinese Population

“…Thus, it may play a role in the pathogenesis www.intechopen.com of HCC-related AFB1. Some recent studies have showed that defects in XPC have been related to many types of malignant tumors (73)(74)(75)(76)(77)(78)(79)(80)(81)(82). Transgenic mice studies also revealed predisposition to many types of tumors in XPC gene knockout mice (83).…”

Arg72Pro TP53 polymorphism and cancer susceptibility: A comprehensive meta‐analysis of 302 case‐control studies

“…Between-study heterogeneity was assessed by calculating Q-statistic and quantified using the I 2 value, a value that describes the percentage of variation across studies that are due to heterogeneity rather than chance, where 0% indicates no observed heterogeneity and larger values show increasing heterogeneity, with 25% regarded as low, 50% as moderate, and 75% as high. 35,36 Publication bias was assessed with funnel plots and Egger's tests. 37 The HWE was tested by the v 2 test for goodness of fit.…”