Hepatitis B and C infections, single nucleotide polymorphisms of the inflammatory pathway, and the risk of non-Hodgkin's lymphoma.

摘要

HIV/AIDS is a major public health problem worldwide and in the United States. Hepatitis B and C viruses (HBV/HCV) are highly prevalent in HIV-positive populations. Infections with either HBV or HCV may adversely complicate the already susceptible immune system of HIV/AIDS patients and increase their risk of developing HIV/AIDS-associated malignancies, such as non-Hodgkin's lymphoma (NHL). Because HIV/AIDS-related NHL is associated with immunusuppression, single nucleotide polymorphisms (SNPs) involved in the inflammatory pathway may also mediate the susceptibility of NHL independently and in conjunction with HBV/HCV and HIV-related clinical markers, such as CD4 cell counts and HIV RNA viral load. This dissertation examines the impact of hepatitis B and C infections and single nucleotide polymorphisms of COX-2, IL-1alpha, IL-1beta, CDH1, and PPARgamma on NHL susceptibility among HIV-infected homo- and bi-sexual men.;A nested case-control design was employed in this study with 188 cases and 691 controls matched by age and the visit at HIV seroconversion or seroprevalence within the Multicenter AIDS Cohort Study (MACS). The antibodies/antigens of HBV and HCV were assayed by ELISA for cases and controls. Genotypes of the inflammation-related SNPs were analyzed using TaqMan and PCR-PFLP methods. Conditional logistic regression models were used to assess potential associations to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Stratified analyses were also employed to explore possible interactions.;HCV infection was positively associated with the risk of NHL and non-CNS lymphoma subtypes with adjustments (OR = 1.88, 95% CI: 1.09-3.21 and OR = 1.86, 95% CI: 1.04-3.31, respectively). However, no obvious association was observed between chronic or past HBV infections with NHL. A positive association was noted between IL1alpha A114S and B-cell non-CNS lymphomas (OR = 1.74, 95% CI: 1.15-2.61). In addition, no clear associations were found between SNPs of the COX-2, IL-1beta, CDH1, and PPARgamma SNPs and NHL. Furthermore, the numbers of risk alleles of the genes in the inflammatory pathway were associated with CNS lymphomas (OR = 1.24, 95% CI: 1.041.50). Our findings suggest that HCV may play an important role in NHL development and that IL1alpha may modulate NHL susceptibility among HIV-infected homo- and bi-sexual men.