association of hadha expression with the risk of breast cancer targeted subset analysis and meta-analysis of microarray data协会hadha表达与乳腺癌的风险分析和目标子集微阵列数据的荟萃分析.pdfVIP

Mamtani and Kulkarni BMC Research Notes 2012, 5:25 /1756-0500/5/25 RESEARCH ARTICLE Open Access Association of HADHA expression with the risk of breast cancer: targeted subset analysis and meta- analysis of microarray data Manju Mamtani1 and Hemant Kulkarni1,2* Abstract 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 resu