Abstract 2869: Interaction between a COX2 polymorphism and ER status in relation to risk for early events in breast cancer patients.

Abstract

Abstract Background. Cyclooxygenase-2 (COX2) polymorphisms are associated with cancer in the lung, colorectum, and breast. In several studies, the COX2 rs5277 variant has been implicated in cancers associated with inflammation. COX-2 is the rate-limiting enzyme in the production of the pro-inflammatory prostaglandin, which activates CYP19 transcription and increases CYP19 (aromatase) levels, the key enzyme in androgen to estrogen conversion. The aim of this study was to investigate whether associations between the COX2 rs5277 polymorphism and early breast cancer events vary according to ER-status. Methods. COX2 rs5277 (306G>C, V102V) was genotyped with PCR based methods in 634 breast cancer patients in a population-based ongoing cohort from southern Sweden. Clinical data were obtained from patient charts and pathology reports. Rs5277 was examined in relation to patient, tumor characteristics and early events. Results. Minor allele frequency was 16.1%. Rs5277 was not associated with patient or tumor characteristics. Median follow-up was 4.92 years in patients with invasive tumors. Overall, increasing number of C-alleles was not associated with early events (Log Rank 1df; p=0.35). However, after stratification according to ER status, increasing number of C-alleles was associated with a fewer early events in the 73 patients with ER-negative tumors (Log Rank 1df; p=0.029) and borderline associated with more early events among the among the 497 patients with ER-positive tumors (Log Rank 1df; p=0.081). The interaction between ER-status and COX2 rs5277 on early events was significant (pinteraction=0.010). In a multivariate model among patients with ER-positive tumors, a CC genotype predicted an increased risk for early events (HR 4.25; 95 %CI 1.18-15.29; p=0.027), adjusted for tumor size (pT), nodal involvement, age, and histological grade. None of the patients with a CC genotype and an ER-negative tumor had a breast cancer event during the follow-up. Conclusion. The results indicate that the association between the COX2 rs5277 polymorphism and early breast cancer events varies according to ER-status. Information on rs5277 genotype may provide additional prognostic information for individual breast cancer patients. Citation Format: Andrea Markkula, Maria Simonsson, Christian Ingvar, Carsten Rose, Helena C. Jernström. Interaction between a COX2 polymorphism and ER status in relation to risk for early events in breast cancer patients. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2869. doi:10.1158/1538-7445.AM2013-2869