The CHEK2 I157T Variant and Breast Cancer Susceptibility: A Systematic Review and Meta-analysis

Background: The cell cycle checkpoint kinase 2 (CHEK2) gene I157T variant may be associated with anincreased risk of breast cancer, but it is unclear whether the evidence is sufficient to recommend testing for themutation in clinical practice. Materials and
Methods: We systematically searched PubMed, Embase, Elsevierand Springer for relevant articles published before Nov 2011. Summary odds ratio (OR) and 95% confidenceinterval (95% CI) incidence rates were calculated using a random-effects model with STATA (version 10.0)software.
Results: A total of fifteen case-control studies, including 19,621 cases and 27,001 controls based on thesearch criteria, were included for analysis. A significant association was found between carrying the CHEK2I157T variant and increased risk of unselected breast cancer (OR = 1.48, 95% CI = 1.31–1.66, P < 0.0001), familialbreast cancer (OR = 1.48, 95% CI = 1.16–1.89, P < 0.0001), and early-onset breast cancer (OR = 1.47, 95% CI =1.29–1.66, P < 0.0001). We found an even stronger significant association between the CHEK2 I157T C variantand increased risk of lobular type breast tumors (OR = 4.17, 95% CI = 2.89–6.03, P < 0.0001).
Conclusion: Ourresearch indicates that the CHEK2 I157T variant may be another important genetic mutation which increasesrisk of breast cancer, especially the lobular type.