Impact of COX2 genotype, ER status and body constitution on risk of early events in different treatment groups of breast cancer patients.
Bottom Line: The COX2 rs5277 (306G>C) polymorphism has been associated with inflammation-associated cancers.Minor allele(C) frequency was 16.1%.Chemotherapy-treated G/G-carriers with a breast volume ≥ 850 ml had an increased risk of early events irrespective of ER status, adjusted HR 8.99 (1.14-70.89).
Affiliation: Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden.Show MeSH
Related in: MedlinePlus
Mentions: Whether the COX2 rs5277 polymorphism is directly associated with inflammation is unclear. The COX2 genotype was not associated with tumor COX-2 expression. The rs5277 SNP may be associated with other unmeasured inflammatory patient characteristics, and the association between rs5277 and the risk of early events is driven by other mediators of inflammation, such as NF-κβ.17 Two of three23,26,27 studies have reported increased risks of inflammation-associated cancers for rs5277 G/G carriers. In the present study, G/G carriers had an increased risk of early events if they had ER-negative tumors; but not if they had ER-positive tumors. In two previous studies, COX-2-mediated inflammation was associated with a poor outcome in ER-negative but not ER-positive breast cancer.11,15 We hypothesize that the G/G genotype increases inflammation and the impact of the SNP on survival and treatment response is modulated by nongenetic host factors and tumor ER status ( Fig. 5). This could be mediated through linkage disequilibrium to an unknown, functional SNP. G/G carriers with ER-negative tumors had an increased risk of early events compared to C-allele carriers with ER-negative tumors. ER-negative tumors may be more sensitive to COX-2 induced Akt-pathway activation,15 which raises the threshold for apoptosis38 and leads to more aggressive tumors.11,15
Affiliation: Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden.