Methylenetetrahydrofolate reductase gene C677T polymorphism and lung cancer: an updated meta-analysis.

OBJECTIVE: Methylenetetrahydrofolate reductase (MTHFR) catalyzes the metabolism of folate and nucleotides needed for DNA synthesis and repair. Variations in MTHFR functions likely play roles in the etiology of lung cancer (LC). So far, several studies between MTHFR C677T polymorphism and LC provide controversial or inconclusive results. METHODS: To better assess the purported relationship, we performed a meta-analysis of 14 publications. Eligible studies were identified by searching the Pubmed, Embase, Web of Science and Google Scholar databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association. RESULTS: Overall, no significant association was detected between the MTHFR C677T polymorphism and LC risk, the same as in race subgroup. However, in the stratified analysis by histological type, significantly increased non-small-cell lung cancer (NSCLC) risk was indicated (T-allele vs. C-allele: OR=1.11, 95%CI=1.03-1.19; TT vs. CC: OR=1.24, 95%CI=1.09-1.41; TC vs. CC: OR=1.11, 95%CI=1.03-1.20 and TT+TC vs. CC: OR=1.09, 95%CI=1.03-1.15). At the same time, ever-smokers who carried T-allele (TT+TC) had a 10% decreased LC risk compared with CC genotype carriers. CONCLUSIONS: Our study provided evidence that the MTHFR 677T null genotype may increase NSCLC risk, however, it may protect ever-smokers against LC risk. Future studies with large sample sizes are warranted to further evaluate this association in more detail.

Phase II study of carboplatin combined with weekly docetaxel in patients with advanced non-small cell lung cancer.

PURPOSE: This phase II study is performed to evaluate the safety, efficacy and tolerability of carboplatin combined with weekly docetaxel in patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: All patients were treated with the combination of docetaxel 35 mg/m(2) by IV infusion over 30-60 min weekly, on days 1, 8, and 15, for 3 weeks followed by 1 week of rest, with intravenous carboplatin (AUC 6) administered immediately afterward on day 1. Cycles were repeated every 28 days. RESULTS: Forty-seven (95.9%) of the 49 patients were assessable for response, one case of complete response and 17 cases of partial response were confirmed, giving an overall response rate of 36.7% (95% CI 23.2-50.2%). The median time to progression and overall survival (OS) for all patients were 5.2 months (95% CI 4.1-6.3 months) and 10.4 months (95% CI 7.3-13.5 months), respectively. The estimate of OS at 12 months was 37.6% (95% CI 24.0-51.2%). The most severe hematologic adverse event was anemia, which occurred with grade 3/4 intensity in 7 (14.9%) patients. Neutropenia occurred with grade 3 intensity in 4 (8.5%) patients. However, no grade 4 neutropenia was observed. Grade 3 nausea/vomiting, diarrhea, asthenia, nail changes, and skin reaction were observed in 6 (12.8%), 3 (6.4%), 2 (4.3%), 2 (4.3%) and 1 (2.1%) patients. Yet, no grade 4 non-hematologic toxicity was observed. CONCLUSIONS: The combination of carboplatin with weekly docetaxel is a tolerated treatment modality with encouraging activity and survival outcome in previously untreated patients with advanced NSCLC.