Abstract 141: Nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 polymorphisms, and breast cancer risk.
Authors: Menegaux Florence , Truong Thérèse , Ajmia Florian , Anger Antoinette , Mulot Claire , Laurent-Puig Pierre , Cordina-Duverger Emilie , Guénel Pascal 
Published: August 2014

Objective: To investigate the role of anti-inflammatory drugs (NSAIDs) in breast cancer occurrence, particularly of selective inhibitors of cyclooxygenase-2 (COX-2), enzyme involved in the immune response to inflammation, as well as the role of genetic polymorphisms in the COX-2 gene and their interactions with NSAIDs in breast cancer risk.

Materials and methods: We conducted a population-based case-control study in two French départements (Côte d'Or, Ille-et-Vilaine) between 2005 and 2008 (CECILE study). An in-person interview was conducted using a standardized questionnaire to obtain information on recognized or suspected risk factors for breast cancer. A self-administered questionnaire was used to obtain information on NSAIDs consumption and was returned by mail by 871 cases (71%) and 915 controls (69%). Blood samples were available for 811 cases and 829 controls and allowed genotyping using a dedicated Illumina chip. Seven tagged SNPs selected in COX-2 (rs20417, rs689466, rs2206593, rs5275, rs5277, rs4648261, rs2745557) were included in the analysis. Odds ratios and 95% confidence intervals were calculated using unconditional logistic regression models adjusted for age and département but also for the known risk factors for breast cancer. The analyses were conducted using a dominant genetic model for each SNP. A multiplicative interaction between genetic polymorphisms and NSAIDs use in the risk of breast cancer was also tested.

Results: A negative association was observed between NSAIDs use and breast cancer (OR = 0.83 [0.68 to 1.01]). This association was more pronounced among women who consumed selective inhibitors of COX-2 (OR = 0.60 [0.37 to 0.98]). We observed a negative association between breast cancer and the absence of the common allele for rs5275 (OR = 0.73 [0.54 to 0.99]) and a positive association close to statistical significance for women with at least one rare allele for rs5277 (OR = 1.22 [0.99 to 1.52]). Odds ratios for interaction between NSAID use and COX-2 polymorphisms was 1.25 (0.96 to 1.64, p = 0.10) for rs20417 and 1. 16 [0.99 to 1.37, p = 0.07) for rs5275.

Conclusion: Our results confirm the negative association between NSAIDs use and the occurrence of breast cancer and reinforce the hypothesis that this association may be more specific to selective inhibitors of COX-2. Our results also indicate that specific polymorphisms of the COX-2 gene may modify the risk of breast cancer associated with NSAIDs use.

Citation Format: Florence Menegaux, Thérèse Truong, Florian Ajmia, Antoinette Anger, Claire Mulot, Pierre Laurent-Puig, Emilie Cordina-Duverger, Pascal Guénel. Nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 polymorphisms, and breast cancer risk. [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 141. doi:10.1158/1538-7445.AM2013-141