BCL-2 (B-cell leukemia/lymphoma 2) gene has been demonstrated to be associated with breast cancer development and a single nucleotide polymorphism (SNP; -938C > A) has been identified recently. To investigate whether this polymorphism functions as a modifier of breast cancer development, we analyzed the distribution of genotype frequency, as well as the association of genotype with clinicopathological characteristics. Furthermore, we also studied the effects of this SNP on Bcl-2 expression in vitro.
We genotyped the BCL-2 (-938C > A) in 114 patients and 107 controls, and analyzed the estrogen receptor (ER), progestogen receptor (PR), C-erbB2 and Ki67 status with immunohistochemistry (IHC). Different Bcl-2 protein levels in breast cancer cell lines were determined using western blot. Logistic regression model was applied in statistical analysis.
We found that homozygous AA genotype was associated with an increased risk (AA vs AC+CC) by 2.37-fold for breast cancer development and significant association was observed between nodal status and different genotypes of BCL-2 (-938C > A) (p = 0.014). AA genotype was more likely to develop into lobular breast cancer (p = 0.036). The result of western blot analysis indicated that allele A was associated with the lower level of Bcl-2 expression in breast cancer cell lines.
AA genotype of BCL-2 (-938C > A) is associated with susceptibility of breast cancer, and this genotype is only associated with the nodal status and pathological diagnosis of breast cancer. The polymorphism has an effect on Bcl-2 expression but needs further investigation.