Terry Mary Beth, Gammon Marilie D, Schoenberg Janet B, Brinton Louise A, Arber Nadir, Hibshoosh Hanina
Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York 10032, USA.
Cancer Epidemiol Biomarkers Prev. 2002 Oct;11(10 Pt 1):1100-3.
Cyclin D1, an important cell cycle regulator, is overexpressed in several human cancers including breast. Both estrogens and progestins activate the transcription of the gene; antiestrogens have been shown to reduce cyclin D1 protein levels. Cyclin D1 protein overexpression has been strongly associated with well-differentiated, estrogen receptor-positive tumors. Little is known, however, as to whether epidemiological risk factors are related to this molecularly defined subset of tumors. Using a population-based study of young women <45 years in New Jersey, we analyzed whether oral contraceptives (OCs) and other risk factors were associated with the overexpression of cyclin D1 in breast cancer tissue. We measured cyclin D1 status in paraffin-embedded, archived tissue from 78.8% of the breast cancer cases using immunohistochemistry. Cyclin D1 was overexpressed in 33.7% of the cases (123 of 365). We used unordered polytomous logistic regression to estimate the odds ratios (ORs) for two case groups--(a) breast cancer with cyclin D1 overexpression (n = 123) and (b) breast cancer without overexpression (n = 242)--compared with 462 population-based controls. The multivariate-adjusted OR for ever use of OCs was 1.6 [95% confidence interval (CI), 1.0-2.5] for cases that overexpressed cyclin D1 and 1.0 (95% CI, 0.7-1.5) for those with no overexpression. Among women who started using OCs at least 20 years before the reference date, the OR was increased 2-fold for breast cancer with cyclin D1 overexpression (OR, 2.2; 95% CI, 1.2-4.0) but not for breast cancer without cyclin D1 overexpression (OR, 1.1; 95% CI, 0.7-1.8). If replicated, these findings suggest that early OC use may be associated with the subset of mammary tumors that overexpress cyclin D1.
细胞周期蛋白D1是一种重要的细胞周期调节因子，在包括乳腺癌在内的多种人类癌症中过度表达。雌激素和孕激素均可激活该基因的转录；抗雌激素已被证明可降低细胞周期蛋白D1的蛋白水平。细胞周期蛋白D1蛋白的过度表达与高分化、雌激素受体阳性肿瘤密切相关。然而，关于流行病学危险因素是否与这种分子定义的肿瘤亚群相关，人们知之甚少。我们利用新泽西州一项针对45岁以下年轻女性的基于人群的研究，分析口服避孕药（OCs）和其他危险因素是否与乳腺癌组织中细胞周期蛋白D1的过度表达有关。我们使用免疫组织化学方法检测了365例乳腺癌病例中78.8%的石蜡包埋存档组织的细胞周期蛋白D1状态。33.7%的病例（365例中的123例）细胞周期蛋白D1过度表达。我们使用无序多分类逻辑回归来估计两个病例组（a）细胞周期蛋白D1过度表达的乳腺癌（n = 123）和（b）无过度表达的乳腺癌（n = 242）与462名基于人群的对照相比的优势比（OR）。对于细胞周期蛋白D1过度表达的病例，曾经使用OCs的多变量调整OR为1.6 [95%置信区间（CI），1.0 - 2.5]，对于无过度表达的病例为1.0（95% CI，0.7 - 1.5）。在参考日期前至少20年开始使用OCs的女性中，细胞周期蛋白D1过度表达的乳腺癌的OR增加了2倍（OR，2.2；95% CI，1.2 - 4.0），但细胞周期蛋白D1无过度表达的乳腺癌则不然（OR，1.1；95% CI，0.7 - 1.8）。如果这些发现得到重复验证，表明早期使用OCs可能与细胞周期蛋白D1过度表达的乳腺肿瘤亚群有关。
