Abstract P4-12-10: Prognostic relevance of caspase 8 polymorphisms for breast cancer

Abstract Background: The minor allele of two caspase 8 polymorphisms, namely CASP8 -652 6N InsDel (rs3834129) and CASP8 Asp302His (rs1045485), were repeatedly associated with reduced breast cancer susceptibility. Contrarily, the presence of the -652 6N Del or the CASP8 302His variant was reported to be an unfavorable prognostic factor in colorectal cancer or neuroblastoma. However, prognostic relevance of these genetic variants for breast cancer is completely unknown and is therefore adressed by the current study. Methods: Genotyping was performed by pyrosequencing. Caspase 8 mRNA expression was quantified by comparative RT-qPCR. Results: We observed an allele-dose dependent association between CASP8 -652 6N InsDel and caspase 8 mRNA expression in breast cancer tissue, with homozygous deletion carriers showing lowest relative caspase 8 expression (p=0.0131). Intriguingly, the presence of the -652 6N Del or the 302His variant was shown to be a negative prognostic factor for breast cancer in terms of an allele-dose dependent influence on overall survival (OS, p=0.0018, p=0.0150, respectively). Moreover, both polymorphisms were independent predictors of OS after adjusting for co-variats (p=0.007, p=0.037, respectively). Prognostic relevance of both polymorphisms was independent from ER or Her2/Neu receptor status and a combined analysis of diplotypes revealed an additive influence on OS (p=0.0002). Conclusion: This is the first report, showing negative and independent prognostic impact of the CASP8 -652 6N Del and the 302His variant for breast cancer. Our data provide rationale to further validate clinical utility of these polymorphisms for breast cancer and to extend this investigation to a broad scope of other malignancies. Citation Format: Wimberger P, Jan Dominik K, Agnes B, Kurt S, Rainer C, Rainer K, Winfried S, Hagen B. Prognostic relevance of caspase 8 polymorphisms for breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-12-10.