Polymorphisms in cycloxygenase-2 gene and breast cancer prognosis: association between PTGS2 haplotypes and histopathological features

Abstract

Cyclooxygenase-2 (COX-2) overexpression is associated with worse prognosis in breast cancer. COX-2 is encoded by a polymorphic gene, called PTGS2, and its expression may be genetically influenced. In this article, we investigate the association between PTGS2 haplotypes and histopathological parameters with prognostic value on the clinical outcome of breast cancer. The study involved 606 women under current treatment for non-metastatic breast cancer. Patients were genotyped for rs689465, rs689466, rs20417, and rs5275, and their haplotypes were inferred. The distribution of PTGS2 genotypes and haplotypes was evaluated according to histopathological categorical groups used for prognostic determination of low/intermediate versus high risk of tumor recurrence. Our results indicate positive associations between variant genotypes of rs689465 and estrogen receptor negativity (OR: 1.59, 95% CI: 1.04-2.44, P: 0.02) or HER2 positivity (OR: 1.79, 95% CI: 1.00-3.18, P: 0.03), and between variant genotypes of rs20417 and estrogen receptor negativity (OR: 1.75, 95% CI: 1.15-2.57, P: 0.005), progesterone receptor negativity (OR: 1.56, 95% CI: 1.09-2.22, P: 0.01) or HER2 positivity (OR: 1.80, 95% CI: 1.04-3.13, P: 0.02). In contrast, variant genotypes of rs689466 are negatively associated with estrogen receptor negativity (OR: 0.57, 95% CI: 0.33-0.98, P: 0.03). A total of eight haplotypes were inferred, and there was a significant difference in their distribution as a function of tumor size (P: 0.011), estrogen receptor status (P: 0.018), and HER2 status (P: 0.025). PTGS2 haplotype *7 (formed by rs689465G, rs689466A, rs20417C, and rs5275T) is positively associated with higher tumor size (OR: 3.72, 95% CI: 1.19-11.22, P: 0.006), estrogen receptor negativity (OR: 2.43, 95% CI: 0.97-5.98, P: 0.032), progesterone receptor negativity (OR: 2.58, 95% CI: 1.05-6.39, P: 0.02), and HER2 positivity (OR: 4.17, 95% CI: 1.19-14.44, P: 0.007). Our results suggest that PTGS2 haplotype *7 may contribute to higher growth of untreated breast cancer and that PTGS2 haplotypes need to be considered in the characterization of breast cancer prognosis.

Functional polymorphisms of the cyclooxygenase-2 gene and prognosis of hepatocellular carcinoma - a cohort study in Chinese people

“…As an inflammation-associated enzyme, COX-2 plays important roles in cell apoptosis, proliferation, differentiation, and angiogenesis, and is thus involved in the pathogenesis of solid tumors (Coskunpinar et al, 2011;Gangwar et al, 2011;Talar-Wojnarowska et al, 2011). Recently, a number of studies have focused on the influence of COX-2 SNPs on risk of various cancers including HCC, but very few have investigated their role in the progression of these diseases (Festa-Vasconcellos et al, 2012).…”

Polymorphisms in cyclooxygenase-2 gene in endometrial cancer patients

“…Breast cancer is an estrogen-dependent tumor, such as EC type 1, in which the main secretory factor inducing aromatase expression in the surrounding stromal cells is the prostaglandin E2 (PGE2) that is synthetized by COX-2 [39]. In breast cancer, the presence of rs5275 T in a certain haplotype might be a risk factor in relation to the growth of untreated breast cancers [40].…”

“…The association between the T8473C (rs5275) polymorphism of COX-2 gene and the increased risk of tumors, often characterized by COX-2 overexpression [21][22][23][24][25][26][27][28][29][30][31][32][33], was described in several original articles.…”

Lack of Association of the Cyclooxygenase-2 Gene 8473T>C Polymorphism with Breast Cancer Risk: a Meta-analysis

“…(Gallicchio et al, 2006;Langsenlehner et al, 2006;Cox et al, 2007;Vogel et al, 2007;Brasky et al, 2011), 2 of Asians group (Gao et al, 2007;Gao et al, 2014), and 3 of other groups (2 Mixed and 1 African) (Shen et al, 2006;Piranda et al, 2010;Fawzy et al, 2013). Among 12 studies in this article, 10 studies were performed in PCC study (Gallicchio et al, 2006;Langsenlehner et al, 2006;Shen et al, 2006;Cox et al, 2007;Vogel et al, 2007;Piranda et al, 2010;Brasky et al, 2011;Festa-Vasconcellos et al, 2012) and 2 in HCC study (Gao et al, 2007;Gao et al, 2014). In addition, genotype and allele distribution for each study were summarized in Table 2.…”