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Background: Southern China is a major area for endemic nasopharyngeal carcinoma (NPC). Genetic factors as well as environmental factors play a role in development of NPC. To investigate the roles of previously described carcinogen metabolism gene variants for NPC susceptibility in a Han Chinese population, we conducted a casecontrol study in two independent study population groups afflicted with NPC in Guangdong and Guangxi Provinces of southern China. Methods: Five single nucleotide polymorphisms (SNPs) of CYP2E1-rs2031920, CYP2E1-rs6413432, GSTP1-rs947894, MPO-rs2333227 and NQO1-rs1800566 were genotyped by PCR-based RFLP, sequencing and TaqMan assay in 358 NPC cases and 629 controls (phase I cohort). Logistic regression analysis was used to estimate odds ratios (OR) and 95% confidence intervals (CI). To confirm our results, sixteen tag SNPs for GSTP1, MPO, NQO1 (which 100% covered these genes), and 4 functional SNPs of CYP2E1 were genotyped in another cohort of 213 NPC cases and 230 controls (phase II cohort). Results: No significant associations in NPC risk were observed for the five polymorphisms tested in the phase I cohort. In an additional stratified analysis for phase I, there was no significant association between cases and controls in NPC high risk population (EBV/IgA/VCA positive population). Analysis of 14 tagging SNPs within the same genes in an independent phase II cohort were in agreement with no SNPs significantly associated with NPC. Conclusions: Our results suggest that polymorphism of CYP2E1, GSTP1, MPO and NQO1 genes does not contribute to overall NPC risk in a Han Chinese in southern China. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV) infection is a significant public health problem that may lead to chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC). Approximately 30% of the world's population has been infected with HBV and approximately 350 million (5-6%) are persistent carriers. More than 120 million Chinese are infected with HBV. The role of host genetic factors and their interactions with environmental factors leading to chronic HBV infection and its complications are not well understood. We believe that a better understanding of these factors and interactions will lead to more effective diagnostic and therapeutic options. Methods/Design: This is a population-based, case-control study protocol to enroll 2200 Han Chinese from medical centers in northern and western China. Adult subjects in the following groups are being enrolled: healthy donors (n = 200), HBV infected persons achieving virus clearance (n = 400), asymptomatic HBV persistent carriers (n = 400), chronic hepatitis B cases (n = 400), decompensated liver cirrhosis with HBV infection cases (n = 400), and hepatocellular carcinoma with HBV infection cases (n = 400). In addition, for haplotype inference and quality control of sample handling and genotyping results, children of 1000 cases will be asked to provide a buccal sample for DNA extraction. With the exception of adult patients presenting with liver cirrhosis or HCC, all other cases and controls will be 40 years or older at enrollment. A questionnaire is being administered to capture dietary and environmental risk factors. Both candidate-gene and genome-wide association approaches will be used to assess the role of single genetic factors and higher order interactions with other genetic or environmental factors in HBV diseases. Conclusion: This study is designed and powered to detect single gene effects as well as gene-gene and environmental-gene interactions. The identification of allelic polymorphisms in genes involved in the pathway leading to chronic viral infection, liver cirrhosis and, ultimately, hepatocellular carcinoma would provide insights to those factors leading to HBV replication, liver inflammation, fibrosis, and the carcinogenic process. An understanding of the contribution of host genetic factors and their interactions may inform public health policy, improve diagnostics and clinical management, and provide targets for drug development. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is a complex disease caused by a combination of Epstein-Barr virus chronic infection, the environment and host genes in a multi-step process of carcinogenesis. The identity of genetic factors involved in the development of chronic Epstein-Barr virus infection and NPC remains elusive, however. Here, we describe a two-phase, population-based, case-control study of Han Chinese from Guangxi province, where the NPC incidence rate rises to a high of 25-50 per 100,000 individuals. Phase I, powered to detect single gene associations, enrolled 984 subjects to determine feasibility, to develop infrastructure and logistics and to determine error rates in sample handling. A microsatellite screen of Phase I study participants, genotyped for 319 alleles from 34 microsatellites spanning an 18-megabase region of chromosome 4 (4p15.1-q12), previously implicated by a linkage analysis of familial NPC, found 14 alleles marginally associated with developing NPC or chronic immunoglobulin A production (p=0.001-0.03). These associations lost significance after applying a correction for multiple tests. Although the present results await confirmation, the Phase II study population has tripled patient enrollment and has included environmental covariates, offering the potential to validate this and other genomic regions that influence the onset of NPC.