Correlation between smoking history and molecular pathways in sporadic colorectal cancer: a meta-analysis

Background: Epidemiological studies have shown that smoking increases the risk for colorectal cancer (CRC). Evidence of the guiding significance of smoking history for molecular classification and molecular targeted anti-tumor therapy is not well established. Aims: To provide indirectly evidence, we conducted a systematic meta-analysis of association between smoking history and different molecular classification. Methods: We searched in multiple databases up to January 2014, and identified 27 eligible studies. All studies were divided into seven groups based on different molecular alteration categories, which are MSI, CIMP, and three molecular pathway-associated gene alterations (APC, KRAS, P53, BRAF mutation, and APC methylation). Crude odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated to evaluate the association. Results: Smoking showed a significantly positive correlation with P53 mutation (exons 4 to 8), BRAF (codon 600) mutation, MSI positivity, and CIMP positivity, with ORs of 1.25 (95% CI: 1.07-1.45), 1.41 (95% CI: 1.18-1.68), 1.28 (95% CI: 1.12-1.47), and 1.23 (95% CI: 1.01-1.50), respectively. However, smoking was not positively correlated with APC (mutation cluster region) and KRAS (codons 12 and 13) mutation in sporadic CRC patients. Conclusions: These findings suggested smoking history occurred with P53 mutation, BRAF mutation, MSI positivity, and CIMP positivity in sporadic CRCs; and could guide those specifically therapeutic designs when molecular classification with genetic test was infeasible. More associated studies should be conducted for strengthening and renewing the current result.