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

BMC Cancer

Research Article

Laura M Amaral¹  Juliana S Festa-Vasconcellos²  Rosane Vianna-Jorge²  Diogo N Piranda²  Anke Bergmann³ 

[1] Divisão de Farmacologia, Coordenação de Pesquisa Instituto Nacional do Câncer - INCA, RJ, Brazil;Divisão de Farmacologia, Coordenação de Pesquisa Instituto Nacional do Câncer - INCA, RJ, Brazil;Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro - UFRJ, RJ, Brazil;Serviço de Fisioterapia, Hospital do Câncer III - INCA, RJ, Brazil;

关键词: Breast Cancer;    Breast Cancer Risk;    Minor Allele Frequency;    SNPs Rs689465;    Risk Association;   

DOI  :  10.1186/1471-2407-10-613

 received in 2010-01-06, accepted in 2010-11-08,  发布年份 2010

来源: Springer

【 摘 要 】

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.

【 授权许可】

Unknown   
© Piranda et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.