A natural copy number variant in the GAEC1 oncogene is associated with breast cancer susceptibility (#46)
The recently discovered GAEC1 oncogene, located at 7q22, has been found to be amplified in esophageal and colorectal cancers and is associated with altered clinical characteristics in those diseases. Amplification studies in these cancers showed variation in copy number in normal tissues, indicating a potential natural copy number variant (CNV) of GAEC1. In this research, the presence of such a CNV and its association with sporadic breast cancer development was tested in a population of 190 Caucasian women with breast cancer and a population of age, sex and ethnicity matched controls. Data produced by qPCR confirmed the presence of a CNV for GAEC1 in both cancer and control populations, with three common copy number types and several uncommon values, representing up to a 64-fold difference in GAEC1 copies. In addition, Chi-square analysis of copy number types indicated that increased GAEC1 copy number is associated with cancer development. This includes analysis using only the common copy number types (p=0.05) as well as considering all genotypes on a High/Low gene dosage basis (p=0.03). Overall risk for breast cancer was found to be slightly increased in high dose individuals (OR 1.552 (95% CI 1.035-2.338)). These results indicate that GAEC1 may be an important gene in the development of breast cancer, and that examination of its copy number in patient DNA may be a useful addition to genetic risk markers in sporadic cases.