Association between genetic polymorphisms of CYP2A13, CYP2A6 and risk of nasopharyngeal carcinoma in southern Chinese population

Background: Cytochrome P450 2A13 (CYP2A13) and 2A6 (CYP2A6) are enzymes expressed in the human respiratory tract, exhibit high efficiency in the metabolic activation of tobacco carcinogen 4(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). A C→T transition in the CYP2A13 gene causes Arg257Cys amino acid substitution and a deletion of the CYP2A6 gene named as CYP2A6 *4, both of them result in a significantly reduced activity toward NNK and other substrates. In this case-control study, we investigated the association between the CYP2A13 and CYP2A6 variants, smoking status and the risk of developing nasopharyngeal carcinoma (NPC) in the Cantonese population living in southern China. Materials and Methods: Genotypes of CYP2A13 and CYP2A6 genes were analyzed by using polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) assays and two-step PCR method. Results: Neither the CYP2A13 -3375T variants nor CYP2A6 *4 variants were associated with risk of NPC (OR = 0.84, 95% CI = 0.59–1.20, and OR = 0.83, 95% CI = 0.58–1.18, respectively) compared with their wild genotypes. Combination analysis showed that individuals with both CYP2A13 CT or TT variants and CYP2A6 *4 variants had no association with risk for NPC (OR = 0.71, 95% CI = 0.33–1.52) compared with those with both CYP2A13 CC and CYP2A6 *1/*1 genotypes. No association with the risk of NPC was observed in smokers with CYP2A13 C/T polymorphisms or smokers with CYP2A6 *4 variant polymorphisms (OR = 0.75, 95% CI = 0.43–1.32, and OR = 0.90, 95% CI = 0.27–1.70; respectively), including after stratification of smoking status. Furthermore, we did not observe association between the combination of two gene polymorphisms and smokers and risk of developing NPC, including the stratification of smoking. Discussions: Based on the results of this study, the effect of these two CYP2A13 and CYP2A6 enzymes may be not so important in developing of NPC as in other cancers, such as lung cancer. [Yun Cao, Xiao-Ping Miao, Yi-Xin Zeng, Dong-Xin Lin, and Jian-Yong Shao. Association between genetic polymorphisms of CYP2A13, CYP2A6 and risk of nasopharyngeal carcinoma in southern Chinese population. Cancer Biology 2011;1(1):1-7]. (ISSN: 2150-1041). http://www.cancer-biology.org.