Abstract
The B-cell CLL/lymphoma 2 (BCL2) gene family encodes pro- and anti-apoptotic proteins that are critical regulators of programmed cell death. Higher levels of BCL2 expression in breast tumours have been shown to be an independent prognostic factor for improved survival from breast cancer. The promoter single nucleotide polymorphism (SNP) rs2279115 has been associated with both BCL2 expression and patient survival. The aim of this study was to attempt to replicate these observations in a cohort of 1015 UK women with breast cancer, and to compare genotype frequencies in cases and controls. In this study, 1015 breast cancer cases and 1034 control subjects were genotyped for the rs2279115 SNP by 5’ nuclease PCR. Paraffin embedded tumour tissue for 342 case subjects was assembled into tissue microarrays, and the level of expression of BCL2 was established by immunohistochemistry. Kaplan Meier survival curves and Cox Proportional Hazards models were used to examine the effect of genotype on patient survival. The effect of SNP genotype on tumour BCL2 protein levels and breast cancer susceptibility was assessed by logistic regression. In this study higher BCL2 expression was significantly associated with improved survival from breast cancer (p = 0.015), in keeping with previous reports. The SNP rs2279115 was not found to be associated with tumour expression of BCL2, (p = 0.77), and neither was it associated with case/control status (p = 0.25). There was no significant association between the SNP and overall survival (p = 0.75). In conclusion, we found that higher tumour BCL2 expression is associated with improved survival from breast cancer, in keeping with previous studies. However, in contrast to a previous report, the promoter SNP rs2279115 was not associated with BCL2 expression or overall survival from breast cancer.
Highlights
The balance between cell proliferation and levels of apoptosis is frequently disrupted in tumours, with tumorigenesis being promoted by both the loss of proapoptotic signals and the gain of anti-apoptotic mechanisms (Hanahan & Weinberg 2000; Hanahan & Weinberg 2011)
In this study higher expression of B-cell chronic lymphocytic leukaemia (CLL)/lymphoma 2 (BCL2) was associated with the A-allele (p = 0.044) and Kaplan-Meier survival analysis revealed a significant association of the AA genotype with improved survival (p = 0.030)
The aim of this study was to use a cohort of breast cancer cases, from the Sheffield Breast Cancer Study (SBCS) to determine whether there is a relationship between the promoter single nucleotide polymorphism (SNP) rs2279115 and tumour protein levels of BCL2, and whether this corresponds to any differences in patient survival
Summary
The balance between cell proliferation and levels of apoptosis is frequently disrupted in tumours, with tumorigenesis being promoted by both the loss of proapoptotic signals and the gain of anti-apoptotic mechanisms (Hanahan & Weinberg 2000; Hanahan & Weinberg 2011). In keeping with these findings BCL2 protein expression in B cells from CLL patients carrying the AA genotype was significantly increased compared with CC genotypes (Nuckel et al 2007) This relationship was demonstrated in relation to lymph node negative breast cancer in one previous study (Bachmann et al 2007). In this study higher expression of BCL2 was associated with the A-allele (p = 0.044) and Kaplan-Meier survival analysis revealed a significant association of the AA genotype with improved survival (p = 0.030) This relationship has been demonstrated in oropharyngeal squamous cell carcinoma (Lehnerdt et al 2009) where rs2279115 was significantly associated with BCL2 expression (p = 0.008) and with overall survival (p = 0.0247). This trend was demonstrated in renal cancer (Hirata et al 2009)
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