Potentially functional polymorphisms in ESR1 and breast cancer risk: a meta-analysis
Potentially functional polymorphisms in ESR1 and breast cancer risk: a meta-analysis
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DOI：
10.1007/s10549-009-0532-9
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发表时间：
2010-05-01
影响因子：
3.8
通讯作者：
Dai, Min
中科院分区：
文献类型：
--
作者：
Li, Ni;Dong, Jing;Dai, Min
雌激素暴露是乳腺癌发展的一个主要危险因素。雌激素受体α（ESR 1）是乳腺组织雌激素反应的关键介质。改变ESR 1表达的遗传变化可能会影响乳腺癌的易感性。自从发现ESR 1基因的几个潜在的功能性多态性（rs 2234693、rs 9340799、rs 1801132、rs3798577、rs 2228480）后，近年来开展了分子流行病学研究，以评估不同人群中多态性与乳腺癌风险的关系。然而，结果仍然相互矛盾，而不是结论性的。目前对10，300例乳腺癌病例和16，620例对照rs 2234693的分析显示，CC和CC/CT携带者的乳腺癌风险显著降低（CC vs. TT：OR，0.92，95%CI，0.86-0.99; CC/CT vs. TT：OR，0.95，95%CI，0.89-1.00）。rs 1801132多态性的变异基因型也与5,649例病例和6,856例对照的显性模型中乳腺癌风险降低相关（GG/GC vs. CC：OR，0.92，95%CI，0.85-0.99）。这些结果表明，潜在的功能性ESR 1多态性可能在乳腺癌易感性中发挥低风险作用。ESR 1中的SNPs rs 9340799、rs3798577、rs 2228480和rs 2077647不是致病性SNPs。SNPs rs 2747648、rs 1062577和rs3020314被推荐用于进一步的关联研究和功能评估。
Estrogen exposure is a central risk factor in the development of breast cancer. Estrogen receptor alpha (coded by ESR1) is the key mediator of estrogen response in mammary tissue. Genetic changes altering the expression of ESR1 is likely to affect breast cancer susceptibility. Since the identification of several potentially functional polymorphisms in ESR1 (rs2234693, rs9340799, rs1801132, rs3798577, rs2228480), molecular epidemiological studies were conducted in recent years to evaluate the association between polymorphisms and breast cancer risk in diverse populations. However, the results remain conflicting rather than conclusive. This current analysis on 10,300 breast cancer cases and 16,620 controls on rs2234693 showed a borderline significant decreased breast cancer risk for CC and CC/CT carriers (CC vs. TT: OR, 0.92, 95% CI, 0.86-0.99; CC/CT vs. TT: OR, 0.95, 95% CI, 0.89-1.00). Variant genotypes of the rs1801132 polymorphism were also associated with a decreased breast cancer risk in a dominant model in 5,649 cases and 6,856 controls (GG/GC vs. CC: OR, 0.92, 95% CI, 0.85-0.99). These results suggest that potentially functional ESR1 polymorphisms may play a low penetrance role in breast cancer susceptibility. SNPs rs9340799, rs3798577, rs2228480, and rs2077647 in ESR1 were not causative SNPs. SNPs rs2747648, rs1062577, and rs3020314 were recommended in further association studies and functional evaluations.