RESUMO
Observational studies have shown an association between liver dysfunction and hepatocellular carcinoma (HCC), but the causality relationship between them is unclear. We aimed to determine whether there is a bidirectional causal relationship between liver function indicators (alanine aminotransferase, ALT; aspartate aminotransferase, AST; alkaline phosphatase, ALP; γ-glutamyltransferase, GGT) and HCC. Our two-sample Mendelian randomization (MR) study acquired single nucleotide polymorphisms (SNPs) associated with liver function indicators (ALT, n = 134,182; AST, n = 134,154; GGT, n = 118,309; ALP, n = 105,030) and with HCC (n = 197,611) from publicly available genome-wide association studies (GWAS) of East Asian ancestry in Japan (BioBank Japan, BBJ). Univariable MR analyses were performed to identify whether the genetic evidence of exposure was significantly associated with outcome. Multivariable MR analysis was conducted to estimate the independent effects of exposures on outcome. Univariable MR analysis indicated that the level of ALT, AST, and GGT was the risk factor for HCC incidence. Meanwhile, multivariable MR analysis revealed that AST was an independent risk factor for HCC. The hazard ratio (HR) of the probability of HCC was 3.045 [95% confidence interval (95%CI), 1.697-5.463, p = 0.003] for AST. The results of reverse MR analyses showed that gene-predictive HCC incidence could increase the levels of AST (HR = 1.031, 95%CI: 1.009-1.054, p = 2.52 × 10-4) and ALT (HR = 1.040, 95%CI: 1.019-1.063, p = 0.005). Meanwhile, HCC may be negatively correlated with ALP levels (HR = 0.971, 95%CI: 0.947-0.995, p = 0.018). This study provides evidence to support that genetically predicted higher levels of AST are related to increased risk of HCC, with no strong evidence of a causal effect of genetically predicted ALP, ALP, and GGT on HCC. In addition, genetic predisposition to HCC could influence blood concentration of ALT, AST, and ALP. Thus, this may create a vicious cycle.
RESUMO
BACKGROUND: About 80% lung cancer is non-small cell lung cancer (NSCLC) and more than 70% are in advanced stage. The aim of this study is to evaluate the clinical efficacy and the side effects of erlotinib in the treatment of elderly patients with advanced non-small cell lung cancer. METHODS: Twenty-nine patients with advanced non-small cell lung cancer were treated with erlotinib 150 mg/d, then the adverse reaction and clinical efficacy were recorded during 3 months. RESULTS: Total 29 patients were evaluated for efficacy. The total rate of effect was 20.69%, including 1 case CR, 5 cases PR, 9 cases SD and 14 cases PD. We compared the effective rate of stage III with IV. There were no significant difference between the effective rate of stage III and IV (P=0.337). The main side effects were rash (37.93%), diarrhea (17.24%) and vomiting (6.9%) and most side effects were grade I and II. CONCLUSIONS: Erlotinib for elderly patients with advanced non-small cell lung cancer have better effective and less toxic effects and the further clinical study should be warranted.
RESUMO
BACKGROUND: About 80% lung cancers belong to non-small cell lung cancer (NSCLC) and more than 70% are in advanced stage. The aim of this study was to evaluate the clinical efficacy and toxicity of erlotinib and GP/TP regimen on advanced non-small cell lung cancer. METHODS: Ninety-one advanced NSCLC patients with different treatments from January 2007 to April 2009 in our hospital were retrospectively analyzed. Ninety-one patients were divided into the erlotinib and TP/GP group. Erlotinib group: received erlotinib 150 mg/dl TP/GP group: the original chemotherapy for advanced non-small cell lung cancer. The cycles were repeated for 21 days. The patients were given docetaxel (80 mg/m(2), d1) or gemcitabine (1 000 mg/m(2), d1, 8) +cisplatin (70 mg/m(2), d2); then the adverse reaction and clinical efficacy were recorded during 3 months. RESULTS: Total 91 patients were evaluated for efficacy. The total rate of effect was 23.33% in erlotinib group. The side effects were erythra, diarrhea and vomiting. Pulmonary fibrosis was found in one patient after 21 days. TP/GP group: the total rate of effect was 27.78% and 28% and the side effects were bone marrow depression and reaction of gastrointestinal tract. There were no significantly difference between the two groups in the total rate of effect (P>0.05). But the side effects were less in erlotinib group, and there were significantly difference between the two groups. CONCLUSIONS: Erlotinib on advanced non-small cell lung cancer shows more effectiveness and adverse reactions are tolerable. The further clinical study should be warranted.