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 an increased risk of breast cancer, but it is unclear whether the evidence is sufficient to recommend testing for the mutation in clinical practice.


METHODS
We systematically searched PubMed, Embase, Elsevier and Springer for relevant articles published before Nov 2011. Summary odds ratio (OR) and 95% confidence interval (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 the search criteria, were included for analysis. A significant association was found between carrying the CHEK2 I157T variant and increased risk of unselected breast cancer (OR = 1.48, 95% CI = 1.31-1.66, P < 0.0001), familial breast 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 variant and increased risk of lobular type breast tumors (OR = 4.17, 95% CI = 2.89-6.03, P < 0.0001).


CONCLUSIONS
Our research indicates that the CHEK2 I157T variant may be another important genetic mutation which increases risk of breast cancer, especially the lobular type.
Department of Oncology, Changhai Hospital, Shanghai, China.
Chuan
C
Liu
Ying
Y
Wang
Qing-Shui
QS
Wang
Ya-Jie
YJ
Wang
D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D064447:Checkpoint Kinase 2; D016001:Confidence Intervals; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D009154:Mutation; D016017:Odds Ratio; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases