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Impact of COX2 genotype, ER status and body constitution on risk of early events in different treatment groups of breast cancer patients.

Markkula A, Simonsson M, Rosendahl AH, Gaber A, Ingvar C, Rose C, Jernström H - Int. J. Cancer (2014)

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).

View Article: PubMed Central - PubMed

Affiliation: Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden.

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The figure shows the hypothesized mechanisms of how COX2 rs5277 genotype impacts the risk of early events differently depending on host factors and ER status of the tumor. References to the steps that have been previously explored are indicted. Endo tx = endocrine treatment.
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fig05: The figure shows the hypothesized mechanisms of how COX2 rs5277 genotype impacts the risk of early events differently depending on host factors and ER status of the tumor. References to the steps that have been previously explored are indicted. Endo tx = endocrine treatment.

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


Impact of COX2 genotype, ER status and body constitution on risk of early events in different treatment groups of breast cancer patients.

Markkula A, Simonsson M, Rosendahl AH, Gaber A, Ingvar C, Rose C, Jernström H - Int. J. Cancer (2014)

The figure shows the hypothesized mechanisms of how COX2 rs5277 genotype impacts the risk of early events differently depending on host factors and ER status of the tumor. References to the steps that have been previously explored are indicted. Endo tx = endocrine treatment.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4225481&req=5

fig05: The figure shows the hypothesized mechanisms of how COX2 rs5277 genotype impacts the risk of early events differently depending on host factors and ER status of the tumor. References to the steps that have been previously explored are indicted. Endo tx = endocrine treatment.
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

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).

View Article: PubMed Central - PubMed

Affiliation: Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden.

Show MeSH
Related in: MedlinePlus