Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
Breast Cancer Res Treat. 2010 Jul;122(1):251-7. doi: 10.1007/s10549-009-0688-3. Epub 2009 Dec 24.
The association between single-nucleotide polymorphisms (SNPs) in the COX-2 gene and breast cancer risk is still ambiguous. We here try to derive a more precise estimation of the relationship by performing a meta-analysis based on currently available evidence from literature. More than 15 SNPs have been studied, and the most studied genetic variants were rs5275, rs5277, and rs20417. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association between each polymorphism and breast cancer risk under the codominant model, dominant model, and recessive model, respectively (nine studies with 6,968 cases and 9,126 controls for rs5275; three studies with 2,901 cases and 3,463 controls for rs20417; two studies with 5,551 cases and 6,208 controls for rs5277). No overall significant associations were observed in single-locus analysis between the three polymorphisms of COX-2 and breast cancer risk, though a borderline significant increased risk of breast cancer was detected with rs5277 in a recessive model (OR: 1.217, 95% CI: 0.958-1.547, P = 0.107). The results were not changed when studies were stratified by ethnicity. In conclusion, the present meta-analysis suggests that none of the most studied three SNPs (rs5275, rs20417, and rs5277) in the COX-2 gene is a conspicuous low-penetrant risk factor for developing breast cancer. There is a need for further large studies into the role of these polymorphisms (especially rs5277) and other potentially functional polymorphisms/haplotypes in the COX-2 gene as breast cancer risk modifiers.
COX-2 基因单核苷酸多态性（SNPs）与乳腺癌风险之间的关联仍不明确。我们在此尝试通过对现有文献证据进行荟萃分析，得出更精确的关系评估。已经研究了超过 15 个 SNPs，其中研究最多的遗传变异是 rs5275、rs5277 和 rs20417。分别使用显性模型、共显性模型和隐性模型下的粗 Odds 比（OR）和 95%置信区间（CI）来评估每个多态性与乳腺癌风险之间的关联强度（rs5275 有 9 项研究，共 6968 例病例和 9126 例对照；rs20417 有 3 项研究，共 2901 例病例和 3463 例对照；rs5277 有 2 项研究，共 5551 例病例和 6208 例对照）。在单基因座分析中，COX-2 基因的三个多态性与乳腺癌风险之间没有总体显著关联，尽管在隐性模型中发现 rs5277 与乳腺癌风险呈临界显著增加（OR：1.217，95%CI：0.958-1.547，P=0.107）。按种族分层后，研究结果没有改变。总之，本荟萃分析表明 COX-2 基因中研究最多的三个 SNPs（rs5275、rs20417 和 rs5277）均不是乳腺癌发生的明显低外显率风险因素。需要进一步进行这些多态性（特别是 rs5277）和 COX-2 基因中其他潜在功能多态性/单倍型作为乳腺癌风险修饰因子的作用的大型研究。
