Department of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
Department of Nephrology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
Cancer Cell Int. 2014 May 6;14:38. doi: 10.1186/1475-2867-14-38. eCollection 2014.
Cyclooxygenase (COX) is a rate-limiting enzyme in prostaglandins synthesis which exists in two isoforms, COX-1 and COX-2. Over-expression of COX-2 was considered to increase the proliferation and enhance the invasiveness of breast cancer cells. It was suggested that genetic variations in COX-2 could influence its expression. Herein, the present study was aimed to investigate the associations between two mostly studied functional polymorphisms (-765 G > C and 8473 C > T) in COX-2 and breast cancer risk in Chinese Han women.
In the hospital-based case-control study, 465 breast cancer patients and 799 cancer-free controls were genotyped for the COX-2 -765 G > C and 8473 C > T polymorphisms using TaqMan assay. We estimated odds ratios (ORs) and 95% confidence intervals (95% CIs) using the logistic regression.
Compared with the wild genotype of -765 G > C, we found a statistically significant increased risk of breast cancer associated with the variant genotypes [GC/CC vs. GG: OR = 1.56, 95% CI = 1.11-2.21]. In the stratified analysis, the increased risk was more predominant among the subgroups of younger subjects (OR = 1.61, 95% CI = 1.00-2.61). Furthermore, the variant genotypes were associated with large tumor size (OR = 3.01, 95% CI = 1.47-6.12). No significant association was observed for the 8473 C > T polymorphism.
Our results suggest that the functional -765 G > C polymorphism in the promoter of COX-2 may influence the susceptibility and progression of breast cancer in the Chinese Han population.
环氧化酶(COX)是前列腺素合成中的限速酶,存在两种同工酶形式,COX-1 和 COX-2。COX-2 的过度表达被认为会增加乳腺癌细胞的增殖和侵袭性。有人认为 COX-2 的遗传变异可能会影响其表达。本研究旨在探讨 COX-2 中两个最常研究的功能多态性(-765G>C 和 8473C>T)与中国汉族女性乳腺癌风险之间的关系。
在基于医院的病例对照研究中,使用 TaqMan 检测法对 465 例乳腺癌患者和 799 例无癌对照者的 COX-2-765G>C 和 8473C>T 多态性进行基因分型。我们使用逻辑回归估计比值比(OR)和 95%置信区间(95%CI)。
与 -765G>C 的野生基因型相比,我们发现变异基因型与乳腺癌风险呈统计学显著相关[GC/CC 与 GG:OR=1.56,95%CI=1.11-2.21]。在分层分析中,在年轻患者亚组中,这种风险增加更为明显[OR=1.61,95%CI=1.00-2.61]。此外,变异基因型与大肿瘤大小相关[OR=3.01,95%CI=1.47-6.12]。8473C>T 多态性与乳腺癌风险无关。
我们的结果表明,COX-2 启动子中的功能性-765G>C 多态性可能影响中国汉族人群乳腺癌的易感性和进展。