Polymorphisms of XRCC1 genes and risk of nasopharyngeal carcinoma in the Cantonese population

Yun Cao 2 Xiao-Ping Miao 1 Ma-Yan Huang 2 Ling Deng 2 Li-Fu Hu 0 Ingemar Ernberg 0 Yi-Xin Zeng 2 Dong-Xin Lin 1 Jian-Yong Shao 0 2 0 Microbiology and Tumor Biology Center, Karolinska Institute , Stockholm S171 77 , Sweden 1 Department of Etiology and Carcinogenesis, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100021 , China 2 The State Key Laboratory of Cancer Biology of Southern China and Department of Experiment, Sun Yat-Sen University Cancer Center , Guangzhou 510060 , China Background: Nasopharyngeal carcinoma (NPC) is one of the most common cancers in southern China. In addition to environmental factors such as Epstein-Barr virus infection and diet, genetic susceptibility has been reported to play a key role in the development of this disease. The x-ray repair cross-complementing group 1 (XRCC1) gene is important in DNA base excision repair. We hypothesized that two common single nucleotide polymorphisms of XRCC1 (codons 194 ArgTrp and 399 ArgGln) are related to the risk of NPC and interact with tobacco smoking. Methods: We sought to determine whether these genetic variants of the XRCC1 gene were associated with the risk of NPC among the Cantonese population in a hospital-based case control study using polymerase chain reaction-restriction fragment length polymorphism analysis. We conducted this study in 462 NPC patients and 511 healthy controls. Results: After adjustment for sex and age, we found a reduced risk of developing NPC in individuals with the Trp194Trp genotype (OR = 0.48; 95% CI, 0.27-0.86) and the Arg194Trp genotype (OR = 0.79; 95% CI, 0.60-1.05) compared with those with the Arg194Arg genotype. Compared with those with the Arg399Arg genotype, the risk for NPC was not significantly different in individuals with the Arg399Gln genotype (OR = 0.82; 95% CI, 0.62-1.08) and the Gln399Gln genotype (OR = 1.20; 95% CI, 0.69-2.06). Further analyses stratified by gender and smoking status revealed a significantly reduced risk of NPC among males (OR = 0.32; 95% CI, 0.140.70) and smokers (OR = 0.34; 95% CI, 0.14-0.82) carrying the XRCC1 194Trp/Trp genotype compared with those carrying the Arg/Arg genotype. No association was observed between Arg399Gln variant genotypes and the risk of NPC combined with smoking and gender. Conclusion: Our findings suggest that the XRCC1 Trp194Trp variant genotype is associated with a reduced risk of developing NPC in Cantonese population, particularly in males and smokers. Larger studies are needed to confirm our findings and unravel the underlying mechanisms. - Background Nasopharyngeal carcinoma (NPC) is one of the most common cancers in the Cantonese population in southern China [1]. Etiological factors include Epstein-Barr virus infection, tobacco smoking, and consumption of salted fish [2-4]. In addition to environmental factors, genetic factors such as chromosomal aberrations, nucleotide polymorphisms of HLA class I and II alleles, glutathione S-transferase M1, and cytochrome P450 2E1 also play a role in the development of NPC [5-9]. Only a few people develop the disease in areas where NPC is endemic even though everyone is exposed to the same environment, suggesting that genetic differences such as single nucleotide polymorphisms (SNP) may contribute to NPC carcinogenesis. Polymorphisms in XRCC1 have been identified at conserved sites, including two SNPs at codons 194 (Arg to Trp) and 399 (Arg to Gln) [10]. These findings suggest that since XRCC1 is essential for removing endogenous and exogenous DNA damage, the Arg399Gln substitution may result in deficient DNA repair [11,12]. On the other hand, the Trp194 allele seemed to be protective against DNA damage, although no significant difference was observed from wild-type in terms of DNA repair capacity. Molecular epidemiological studies investigating the Arg194Trp and Arg399Gln variants of XRCC1 and their impact on cancer risk have generated inconsistent results. The Arg194 allele is associated with an increased risk of gastric cardia cancer (adjusted OR = 1.86, 95% CI, 1.09 3.20), and the Gln399 allele is associated with an increased risk of gastric cancer (adjusted OR = 1.53, 95% CI, 0.982.39) [13]. Olshan et. al. reported a weak increase in the risk of head and neck cancer associated with the Arg194Trp polymorphism (OR = 1.3, 95% CI, 0.62.9) and a decreased risk for the Arg399Gln polymorphism (OR = 0.6; CI = 0.41.1) [14]. Other studies have reported that these two XRCC1 variants are associated with elevated risks of esophageal cancer [15], pancreatic adenocarcinoma [16], and breast cancer [17]. In the present study, we investigated the association between the Arg194Trp and Arg399Gln variants of XRCC1, smoking status, and the risk of developing NPC in the Cantonese population living in southern China. Methods Study subjects The study group consisted of 462 patients with histologically confirmed, untreated NPC and 511 cancer-free controls. All subjec (...truncated)