Divisão de Farmacologia, Coordenação de Pesquisa Instituto Nacional do Câncer - INCA, RJ, Brazil.
BMC Cancer. 2010 Nov 8;10:613. doi: 10.1186/1471-2407-10-613.
Cyclooxygenase-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.
The 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.
The 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.
Our results indicate no strong association between the four most frequent PTGS2 SNPs and the risk of breast cancer.
环氧化酶-2（COX-2）在多种类型的癌症中上调，并且假设 COX-2 表达可能受到遗传影响。在这里，我们评估了 COX-2 基因（PTGS2）中的单核苷酸多态性（SNP）与巴西女性乳腺癌发生之间的关联。
该研究分两步进行前瞻性研究：首先，我们从 67 名健康巴西人中筛选 PTGS2 的启动子区域和 3'非翻译区的三个片段，以鉴定 SNP 并选择最小等位基因频率（MAF）至少为 0.10 的 SNP。进一步在 402 名健康志愿者中对这些选定的 SNP 的 MAF 进行特征描述，以评估与异质种族混合相关的潜在差异，并估计 SNP 之间的连锁不平衡。第二步是一项病例对照研究，纳入 318 例患者和 273 例对照，旨在评估 PTGS2 基因型或单体型相关的乳腺癌风险。
筛选分析表明，有 9 个 SNP 的 MAF 如下：rs689465（0.22）、rs689466（0.15）、rs20415（0.007）、rs20417（0.32）、rs20419（0.015）、rs5270（0.02）、rs20424（0.007）、rs5275（0.22）和 rs4648298（0.01）。进一步研究了 rs689465、rs689466、rs20417 和 rs5275：它们的基因型分布符合哈迪-温伯格平衡，并且 MAF 不受性别或肤色影响。在三种可能的两两组合中检测到 rs689465、rs20417 和 rs5275 的强连锁不平衡。在病例对照研究中，与对照组相比，病例中 rs5275TC 杂合子明显增加（OR=1.44，95%CI=1.01-2.06；P=0.043），仅在病例中检测到由 rs689465G、rs689466A、rs20417G 和 rs5275C 形成的单体型。rs5275CC 纯合子或最常见的 rs5275 含单体型与乳腺癌的明显相关性未得到证实。
我们的结果表明，PTGS2 中四个最常见的 SNP 与乳腺癌风险之间没有强烈关联。
