雌激素受体α基因单倍型与绝经后乳腺癌风险：一项病例对照研究。
Oestrogen receptor alpha gene haplotype and postmenopausal breast cancer risk: a case control study.
作者信息
Wedrén Sara, Lovmar Lovisa, Humphreys Keith, Magnusson Cecilia, Melhus Håkan, Syvänen Ann-Christine, Kindmark Andreas, Landegren Ulf, Fermér Maria Lagerström, Stiger Fredrik, Persson Ingemar, Baron John, Weiderpass Elisabete
机构信息
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
出版信息
Breast Cancer Res. 2004;6(4):R437-49. doi: 10.1186/bcr811. Epub 2004 Jun 4.
INTRODUCTION
Oestrogen receptor alpha, which mediates the effect of oestrogen in target tissues, is genetically polymorphic. Because breast cancer development is dependent on oestrogenic influence, we have investigated whether polymorphisms in the oestrogen receptor alpha gene (ESR1) are associated with breast cancer risk.
METHODS
We genotyped breast cancer cases and age-matched population controls for one microsatellite marker and four single-nucleotide polymorphisms (SNPs) in ESR1. The numbers of genotyped cases and controls for each marker were as follows: TAn, 1514 cases and 1514 controls; c.454-397C --> T, 1557 cases and 1512 controls; c.454-351A --> G, 1556 cases and 1512 controls; c.729C --> T, 1562 cases and 1513 controls; c.975C --> G, 1562 cases and 1513 controls. Using logistic regression models, we calculated odds ratios (ORs) and 95% confidence intervals (CIs). Haplotype effects were estimated in an exploratory analysis, using expectation-maximisation algorithms for case-control study data.
RESULTS
There were no compelling associations between single polymorphic loci and breast cancer risk. In haplotype analyses, a common haplotype of the c.454-351A --> G or c.454-397C --> T and c.975C --> G SNPs appeared to be associated with an increased risk for ductal breast cancer: one copy of the c.454-351A --> G and c.975C --> G haplotype entailed an OR of 1.19 (95% CI 1.06-1.33) and two copies with an OR of 1.42 (95% CI 1.15-1.77), compared with no copies, under a model of multiplicative penetrance. The association with the c.454-397C --> T and c.975C --> G haplotypes was similar. Our data indicated that these haplotypes were more influential in women with a high body mass index. Adjustment for multiple comparisons rendered the associations statistically non-significant.
CONCLUSION
We found suggestions of an association between common haplotypes in ESR1 and the risk for ductal breast cancer that is stronger in heavy women.
引言
雌激素受体α介导雌激素在靶组织中的作用，其具有基因多态性。由于乳腺癌的发生依赖于雌激素的影响，我们研究了雌激素受体α基因（ESR1）中的多态性是否与乳腺癌风险相关。
方法
我们对乳腺癌病例和年龄匹配的人群对照进行了ESR1中一个微卫星标记和四个单核苷酸多态性（SNP）的基因分型。每个标记的基因分型病例和对照数量如下：TAn，1514例病例和1514例对照；c.454 - 397C→T，1557例病例和1512例对照；c.454 - 351A→G，1556例病例和1512例对照；c.729C→T，1562例病例和1513例对照；c.975C→G，1562例病例和1513例对照。使用逻辑回归模型，我们计算了比值比（OR）和95%置信区间（CI）。在探索性分析中，使用期望最大化算法对病例对照研究数据估计单倍型效应。
结果
单个多态性位点与乳腺癌风险之间没有明显关联。在单倍型分析中，c.454 - 351A→G或c.454 - 397C→T与c.975C→G SNPs的一种常见单倍型似乎与导管乳腺癌风险增加相关：在乘法外显率模型下，与无该单倍型相比，c.454 - 351A→G和c.975C→G单倍型的一个拷贝的OR为1.19（95%CI 1.06 - 1.33），两个拷贝的OR为1.42（95%CI 1.15 - 1.77）。与c.454 - 397C→T和c.975C→G单倍型的关联相似。我们的数据表明，这些单倍型在体重指数高的女性中影响更大。对多重比较进行校正后，这些关联在统计学上无显著性。
结论
我们发现ESR1中的常见单倍型与导管乳腺癌风险之间存在关联的迹象，且在体重较重的女性中这种关联更强。
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