CD24 polymorphisms in breast cancer: impact on prognosis and risk

Abstract

Overexpression of CD24 has a negative impact on breast cancer prognosis. We have recently reported that the CD24 codon 57 Val/Val genotype (rs52812045) is associated with pathologic complete response after neoadjuvant chemotherapy for primary breast cancer and correlates with intratumoral lymphocyte infiltrates. This study was performed to investigate the influence of CD24 polymorphisms on breast cancer prognosis and risk. A total of 2,514 patients and 4,858 controls recruited as part of the MARIE study, a population-based case-control study, were genotyped for two CD24 polymorphisms (rs52812045, rs3838646) using TaqMan custom genotyping assays. Associations with overall and breast cancer-specific survival were assessed using uni- and multivariable Cox regression models stratified by age at diagnosis and adjusted for prognostic factors. Conditional logistic regression analysis adjusted for major risk factors was used to estimate multivariable odds ratios for risk of putative allele carriers compared to wildtype carriers. CD24 Ala/Val was significantly associated with breast cancer prognosis [Val/Val hazard ratio (HR)(adjusted)=1.52; 95% confidence interval (CI): 1.00-2.30, p=0.05 and HR(adjusted)=1.83; 95% CI: 1.10-3.05, p=0.018 for all-cause and breast cancer-specific mortality, respectively). The association was significant only in patients with a BMI<25 and in those who received adjuvant chemotherapy. None of the CD24 alleles was associated with breast cancer risk. These results provide further evidence of the CD24 Val/Val genotype influencing outcome in primary breast cancer. Together with previous data of CD24 overexpression as a poor prognostic marker, the findings underline the biological importance of CD24 for breast cancer.