Bone morphogenetic protein-4 polymorphism and colorectal cancer risk: a meta analysis

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Abstract
BMP4 rs4444235 is a candidate susceptibility allele that has been associated with an increased risk of colorectal cancer. This study was conducted to examine the association between BMP4 rs4444235 polymorphism and colorectal cancer risk. Odds ratio (ORs) with 95% CIs was pooled as effect indicator. A comprehensive search of related publications was conducted and those which met the inclusion criteria were included. Test of heterogeneity, meta-regression, subgroup analysis, cumulative meta-analysis, assessment of publication bias, and sensitivity test were performed using Stata 11.0. 8 articles on rs4444235 including 19,893 cases and 22,106 controls were included. There was slight heterogeneity which may come from ethnicity and source of control. Pooled results for all five genetic models were statistically significant. ORs were 1.063 (95% CI = (1.034, 1.092)), 1.081 (95% CI = (1.028, 1.136)), and 1.166(95% CI = (1.081, 1.258)) for C versus T, TC versus TT, and CC versus TT comparisons respectively. In Caucasian population, carriers of C allele, CC genotype and TC genotype were at an increased risk of developing CRC, with an OR of 1.079 (95% CI = (1.044, 1.114)), 1.095 (95% CI = (1.034, 1.159)), and 1.199 (95% CI = (1.117,1.287)) respectively. Cumulative meta-analysis indicated that pooled ORs were approximating 1.1 with publication year passing. No significant publication bias was suggested. Sensitivity test indicated stable results. In conclusion, BMP4-rs4444235 polymorphism is probably associated with CRC risk, and C allele is a possible risk factor in overall population. The same conclusion was drawn in Caucasians, but no significant results were obtained in other ethnic populations probably due to limited sample sizes.

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