Polymorphisms in regulatory regions of Cyclooxygenase-2 gene and breast cancer risk in Brazilians: a case-control study

Abstract

BackgroundCyclooxygenase-2 (COX-2) is up-regulated in several types of cancer, and it is hypothesized that COX-2 expression may be genetically influenced. Here, we evaluate the association between single-nucleotide polymorphisms (SNPs) in the COX-2 gene (PTGS2) and the occurrence of breast cancer among Brazilian women.MethodsThe study was conducted prospectively in two steps: First, we screened the promoter region and three fragments of the 3'-untranslated region of PTGS2 from 67 healthy Brazilians to identify SNPs and to select those with a minor allele frequency (MAF) of at least 0.10. The MAF of these selected SNPs was further characterized in 402 healthy volunteers to evaluate potential differences related to heterogeneous racial admixture and to estimate the existence of linkage disequilibrium among the SNPs. The second step was a case-control study with 318 patients and 273 controls designed to evaluate PTGS2 genotype- or haplotype-associated risk of breast cancer.ResultsThe screening analysis indicated nine SNPs with the following MAFs: rs689465 (0.22), rs689466 (0.15), rs20415 (0.007), rs20417 (0.32), rs20419 (0.015), rs5270 (0.02), rs20424 (0.007), rs5275 (0.22) and rs4648298 (0.01). The SNPs rs689465, rs689466, rs20417 and rs5275 were further studied: Their genotypic distributions followed Hardy-Weinberg equilibrium and the MAFs were not affected by gender or skin color. Strong linkage disequilibrium was detected for rs689465, rs20417 and rs5275 in the three possible pairwise combinations. In the case-control study, there was a significant increase of rs5275TC heterozygotes in cases compared to controls (OR = 1.44, 95% CI = 1.01-2.06; P = 0.043), and the haplotype formed by rs689465G, rs689466A, rs20417G and rs5275C was only detected in cases. The apparent association with breast cancer was not confirmed for rs5275CC homozygotes or for the most frequent rs5275C-containing haplotypes.ConclusionsOur results indicate no strong association between the four most frequent PTGS2 SNPs and the risk of breast cancer.

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

“…Genetic variations in the 8473T>C polymorphisms of COX-2 gene may contribute to increased stability of mRNA and the synthesis of COX-2 (Piranda et al, 2010). Researchers from Cox et al have reported three separate studies in the American population to test the hypothesis that polymorphisms in COX-2 are associated with BC risk (Cox et al, 2007).…”

“…(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.…”

-765 G>C POLYMORPHISM OF THE COX-2 GENE AND GASTRIC CANCER RISK IN BRAZILIAN POPULATION

“…We found that the C allele occurs at a frequency of 20.6% in the GC patients. A high percentage of C allele had been observed among Portuguese (19) , Brazilian (21) , and Dutch patients (25) (22%, 32% and 41%, respectively). Studies on European and American populations have reported a higher prevalence of C allele than studies involving Asian (2,4,10) .…”

“…Since the identification of the COX-2 -765G>C polymorphism (18) , studies have shown a correlation between this polymorphism and different types of cancer (3,21,25,30) . In this study we observed the frequency of the COX-2 -765 G/G, GC and CC genotypes were 59%, 34% and 7% in GC patients were similar to those previously reported by Pereira et al (19) for a Portuguese population (49%, 44% and 7%, respectively).…”

Lack of association between the cyclooxygenase 2 -765G>C polymorphism and prostate cancer risk: a meta-analysis

“…Over the last decade, numerous molecular epidemiological case-control studies have been conducted in diverse ethnic backgrounds to explore the association between the COX2 -765G>C polymorphism and risks of various cancers, including breast cancer (Piranda et al, 2010), colorectal carcinoma (Daraei et al, 2012), esophageal (Bye et al, 2011) and gastric cancers , hepatocellular carcinoma (He et al, 2012), leukemia (Zheng et al, 2011), lung cancer (Coskunpinar et al, 2011), lymphoma (Monroy et al, 2011), ovarian (Agachan Cakmakoglu et al, 2011, head and neck (Peters et al, 2009), pancreatic (Zhao et al, 2009), skin (Cocoş et al, 2012), and cervical cancers (Pandey et al, 2010), among others. However, due to the relatively small sample sizes, the results obtained from these studies have been inconclusive or even controversial.…”