Association between the NBS1 Glu185Gln polymorphism and breast cancer risk: a meta-analysis.

Abstract

Nijmegen breakage syndrome 1 (NBS1), a vital DNA repair protein in the homologous recombination repair pathway and a signal modifier in the intra-S phase checkpoint, plays a critical role in cellular response to DNA damages and the maintenance of genomic stability. The NBS1 Glu185Gln (NBS1 E185Q, NBS1 8360G>C, rs1805794) polymorphism has been indicated to be involved in the development of cancer, but results of previous individual studies on the association between NBS1 Glu185Gln polymorphism and breast cancer risk remain controversial and inconclusive. Our meta-analysis investigated this association for the first time by pooling the odds ratios with corresponding 95 % confidence intervals (95 % CIs) of all individual publications available to date. Overall, 14 separate studies with 6,642 cases and 7,138 controls were finally included into the present meta-analysis after a comprehensive literature search of the PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases up to October 21, 2012. Overall analysis and subgroup analyses by ethnicity and source of controls were performed. Meta-analysis of total studies showed that the NBS1 Glu185Gln variant carriers were not susceptible to breast cancer (ORGln vs. Glu = 1.05, 95 % CI 0.80-1.39, P OR = 0.719; OR Gln/Gln vs. Glu/Glu = 0.82, 95 % CI 0.62-1.08, P OR = 0.154; OR Glu/Gln vs. Glu/Glu = 1.00, 95 % CI 0.90-1.13, P OR = 0.939; ORGln/Gln + Glu/Gln vs. Glu/Glu = 0.96, 95 % CI 0.83-1.11, P OR = 0.551; ORGln/Gln vs. Glu/Glu + Glu/Gln = 0.84, 95 % CI 0.67-1.05, P OR = 0.134). Similar results were observed in heterogeneity-adjusted meta-analysis of all studies. Furthermore, subgroup analyses by ethnicity and source of controls did not identify any appreciable relationship of the NBS1 Glu185Gln polymorphism with breast cancer susceptibility in any populations. Sensitivity analysis by sequentially omitting individual studies confirmed the stability and reliability of our results. Our meta-analysis of currently available data shows no association between the NBS1 Glu185Gln polymorphism and breast cancer risk.

• Authors: Fan Yao, Yue Fang, Bo Chen, Feng Jin, Shubao Wang
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 34 Issue 2 Pg. 1255-62 (Apr 2013) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 23381647 (Publication Type: Journal Article, Meta-Analysis)

Chemical References

• Cell Cycle Proteins
• NBN protein, human
• Nuclear Proteins

Topics

• Breast Neoplasms (etiology)
• Case-Control Studies
• Cell Cycle Proteins (genetics)
• Female
• Genetic Predisposition to Disease
• Humans
• Nuclear Proteins (genetics)
• Polymorphism, Genetic (genetics)
• Risk Factors