While several epidemiological studies have investigated the association between vitamin C and risk of esophageal cancer, the results remain inconsistent. In the present study, a meta-analysis was conducted to assess the impact of dietary vitamin C intake on esophageal cancer risk. Online databases were searched up to March 29, 2015, for studies on the association between dietary vitamin C intake and esophageal cancer risk. Pooled risk ratios (RRs) or odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Dose-response analyses were performed using the method of restricted cubic splines with four knots at percentiles of 5, 35, 65 and 95% of the distribution. Publication bias was estimated using Egger's tests and funnel plots. In all, 15 articles were included in this meta-analysis, including 20 studies, containing 7063 controls and 3955 cases of esophageal cancer. By comparing the highest vs. the lowest categories of vitamin C intake, we found that vitamin C was inversely associated with the risk of esophageal cancer [overall OR 5 0.58, 95% CI 5 0.49-0.68, I 2 5 56%]. A linear dose-response relationship was found. With an increase in dietary vitamin C intake of 50 mg/day, the risk of esophageal cancer statistically decreased by 13% (OR 5 0.87, 95% CI 5 0.80-0.93, p linearity 5 0.0002). In conclusion, our analysis suggested that the higher intake of dietary vitamin C might have a protective effect against esophageal cancer.Esophageal cancer ranks the tenth most common malignancy and the eighth leading cause of cancer-related deaths worldwide. 1 In 2012, [mt]456,000 newly diagnosed cases and 400,000 related deaths were reported. 2 Most esophageal cancer patients are diagnosed at the advanced stages, and the 5-year survival rate is <20%. 3 Thus, primary prevention of esophageal cancer is becoming critical.A large proportion of cases are induced by the action of chemical carcinogens. The epidemiological evidence suggests that alcohol consumption, smoking tobacco, N-nitroso compound and micronutrient deficiency are among the major risk factors for esophageal cancer. [4][5][6] The ultimate reactive and carcinogenic forms of most chemical carcinogens are strong electrophiles. 7 However, vitamin C can prevent carcinogenesis of esophageal cells by blocking the formation of Nnitroso compounds. [8][9][10][11][12] Since the first study that explored the association between vitamin C and esophageal cancer in 1987, 13 a number of epidemiological studies have investigated the relationship between vitamin C intake and esophageal cancer risk. However, these results are controversial. Therefore, we conducted a meta-analysis to assess the association of dietary vitamin C intake and the risk of esophageal cancer, and to evaluate the dose-response relationship of esophageal cancer and vitamin C intake.
Material and Methods
Search strategyA comprehensive literature search of Pubmed, and Web of Knowledge was conducted before March 2015. The following keywords were used: "esophageal cancer" or...