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Background: To date, the association between 8q24.21-rs6983267 (T>G) polymorphism and risk of digestive tract cancer remains inconclusive.To derive a more precise estimation of the association, we conducted a meta-analysis on all eligible case-control studies involving 38,262 cases and 47,751 controls.Methods: A comprehensive search was conducted to identify all eligible studies of 8q24.21-rs6983267 (T>G) polymorphism and digestive tract cancer risk.The pooled odds ratio (OR) and the 95% confidence interval (95% CI) were calculated using a fixed or random effect model.Heterogeneity, publication bias, and sensitivity analysis were also explored.Results: Overall, the variant G allele of rs6983267 T>G could significantly increase the risk of digestive tract cancer in all the four genetic models (heterozygote comparison, TG vs.TT: OR =1.19, 95% CI =1.15-1.23, P <0.001, I2 =18.4%;homozygote comparison, GG vs.TT: OR =1.33, 95% CI =1.25-1.43, P < 0.001, I2 =53.3%;dominant model, TG/GG vs.TT: OR =1.24, 95% CI =1.20-1.28, P < 0.001, I2 =30.3%;recessive model GG vs.TG/TT: OR =1.20, 95% CI =1.13-1.27, P < 0.001, I2 =59.8%).Subgroup analysis by cancer types showed that rs1130409 T>G polymorphism is associated with increased risk of gastric cancer, colorectal cancer, throat cancer and liver cancer, but not esophagus cancer.In the stratified analysis by ethnicity, every genetic comparison produced significantly increased risks both in the Asian and Caucasians group.Considering the control source, both hospital-based and population-based controls showed elevated risks in all genetic comparisons.Conclusion: Our study indicated that 8q24.21-rs6983267 (T>G) polymorphism was significantly associated with increased risk of digestive tract cancer.Due to some minor limitations, our findings should be confirmed in further studies.