There are inconsistent data on the association of risk of hepatitis virus infection and hepatitis virus-related diseases with the toll-like receptor 3 (TLR3) gene.Several common polymorphism sites were targeted to assess the risk of HBV infection, HCV infection, and HBV-related diseases.Meta-analysis combining data for 3547 cases and 2797 controls from 8 studies was performed in this study. Pooled ORs were calculated to measure the risk of hepatitis virus infection and hepatitis virus-related diseases. Fixed-effects pooled ORs were calculated using the Mantel-Haenszel method.The TLR3 gene was associated with a significantly increased risk of HBV-related diseases among 1355 patients and 1130 controls ([pooled OR, [95%CI]: 1.30, [1.15–1.48] for dominant; 1.77, [1.35–2.31] for recessive; 1.28 [1.16–1.41] for allele frequency). Subgroup analyses by a polymorphism site indicated an increased risk of HCV infection in relation to the TT/CT genotypes of rs3775291 (1.50 [1.11–2.01]), and a decreased risk ascribed to the T allele (0.20 [0.16–0.25]). We also noted an association between rs3775291 and significantly increased risk of HBV-related diseases (2.23 [1.55–3.21]). No significant inter-study heterogeneity or publication bias was detected in the analyses.These data suggest a likely effect on the risk to infect HCV and develop HBV-related diseases for the TLR3 gene. Large-scale studies with racially diverse populations are required to validate these findings.
ABSTRACT. The aim of this study was to define the genotypes of UGT1A1 and ERCC1 and to examine their relationship with the efficacy and toxicity of a combination therapy of irinotecan and cisplatin in patients with advanced ovarian cancer. The allelic frequencies of the UGT1A1 and ERCC1 variants in a group of 89 patients with advanced ovarian cancer were determined. The relationship between the adverse events of irinotecan-based chemotherapy and the efficacy of cisplatin in patients with advanced ovarian cancer were analyzed. For patients who carried the UGT1A1*28 wild-type (WW) or the UGT1A1*28 heterozygous and homozygous mutant (WM+MM) genotypes, the incidences of grade 2 or 3 tardive diarrhea were 52.2 and 72.7% respectively, and the difference was statistically significant (P = 0.031, OR = 2.1, 95%CI = 1.6-9.2). For grade 3 or 4 tardive diarrhea, the incidence rates were 7.5 and 36.4% respectively; this difference was also statistically significant (P = 0.000, OR = 4.9, 95%CI = 3.3-15.8). The response rates of ERCC1 WW and ERCC1 WM+MM carriers were 30.3 and 20.2% respectively; this difference was significant (P = 0.032, OR = 3.2, 95%CI = 1.4-9.1). Together, the results from this study suggest that UGT1A1 is a target gene for tardive diarrhea, and that the UGT1A1*28 gene mutation might increase the risk of diarrhea with irinotecan-based chemotherapy. Furthermore, the results suggest that ERCC1 WW carriers might obtain a better rate of clinical response from a combined irinotecan and cisplatin regimen than ERCC1 WM+MM carriers.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.