Association of HADHA expression with the risk of breast cancer: targeted subset analysis and meta-analysis of microarray data

BMC Research Notes

Hemant Kulkarni²  Manju Mamtani¹ 

[1] Lata Medical Research Foundation, Nagpur, India;Texas Biomedical Research Institute, 7620 NW Loop 410, San Antonio, Texas 78227-5301, USA

关键词: Meta-analysis;    Microarray;    Gene expression profiling;    HADHA gene;    Breast cancer;   

Others  :  1166786
DOI  :  10.1186/1756-0500-5-25

 received in 2011-09-20, accepted in 2012-01-12,  发布年份 2012

【 摘 要 】

Background

The role of n-3 fatty acids in prevention of breast cancer is well recognized, but the underlying molecular mechanisms are still unclear. In view of the growing need for early detection of breast cancer, Graham et al. (2010) studied the microarray gene expression in histologically normal epithelium of subjects with or without breast cancer. We conducted a secondary analysis of this dataset with a focus on the genes (n = 47) involved in fat and lipid metabolism. We used stepwise multivariate logistic regression analyses, volcano plots and false discovery rates for association analyses. We also conducted meta-analyses of other microarray studies using random effects models for three outcomes--risk of breast cancer (380 breast cancer patients and 240 normal subjects), risk of metastasis (430 metastatic compared to 1104 non-metastatic breast cancers) and risk of recurrence (484 recurring versus 890 non-recurring breast cancers).

Results

The HADHA gene [hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase (trifunctional protein), alpha subunit] was significantly under-expressed in breast cancer; more so in those with estrogen receptor-negative status. Our meta-analysis showed an 18.4%-26% reduction in HADHA expression in breast cancer. Also, there was an inconclusive but consistent under-expression of HADHA in subjects with metastatic and recurring breast cancers.

Conclusions

Involvement of mitochondria and the mitochondrial trifunctional protein (encoded by HADHA gene) in breast carcinogenesis is known. Our results lend additional support to the possibility of this involvement. Further, our results suggest that targeted subset analysis of large genome-based datasets can provide interesting association signals.

【 授权许可】

   
2011 Mamtani et al; licensee BioMed Central Ltd.

【 图 表 】

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