Association of several loci of SMAD7 with colorectal cancer: A meta-analysis based on case-control studies

Background: Sma-and mad-related protein 7 (SMAD7) can affect tumor progression by closing transforming growth factor-beta intracellular signaling channels. Despite the extensive research on the correlation between SMAD7 polymorphisms and colorectal cancer (CRC), the conclusions of studies are still contradictory. We conducted a study focusing on the association of SMAD7 polymorphisms rs4939827, rs4464148, and rs12953717 with CRC.

Methods: We searched through 5 databases for articles and used odd ratios (ORs) and 95% confidence intervals (CIs) to discuss the correlation of SMAD7 polymorphisms with CRC risk. The heterogeneity will be appraised by subgroup analysis and meta-regression. Contour-enhanced funnel plot, Begg test and Egger test were utilized to estimate publication bias, and the sensitivity analysis illustrates the reliability of the outcomes. We performed False-positive report probability and trial sequential analysis methods to verify results. We also used public databases for bioinformatics analysis.

Results: We conclusively included 34 studies totaling 173251 subjects in this study. The minor allele (C) of rs4939827 is a protective factor of CRC (dominant, OR/[95% CI] = 0.89/[0.83-0.97]; recessive, OR/[95% CI] = 0.89/[0.83-0.96]; homozygous, OR/[95% CI] = 0.84/[0.76-0.93]; heterozygous, OR/[95% CI] = 0.91/[0.85-0.97]; additive, OR/[95% CI] = 0.91/[0.87-0.96]). the T allele of rs12953717 (recessive, OR/[95% CI] = 1.22/[1.15-1.28]; homozygous, OR/[95% CI] = 1.25/[1.13-1.38]; additive, OR/[95% CI] = 1.11/[1.05-1.17]) and the C allele of rs4464148 (heterozygous, OR/[95% CI] = 1.13/[1.04-1.24]) can enhance the risk of CRC.

Conclusion: Rs4939827 (T > C) can decrease the susceptibility to CRC. However, the rs4464148 (T > C) and rs12953717 (C > T) variants were connected with an enhanced risk of CRC.