Einarsdóttir Kristjana, Rylander-Rudqvist Tove, Humphreys Keith, Ahlberg Susanne, Jonasdottir Gudrun, Weiderpass Elisabete, Chia Kee Seng, Ingelman-Sundberg Magnus, Persson Ingemar, Liu Jianjun, Hall Per, Wedrén Sara
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Breast Cancer Res. 2005;7(6):R890-6. doi: 10.1186/bcr1319. Epub 2005 Sep 14.
The c.1-34T>C 5' promoter region polymorphism in cytochrome P450c17 (CYP17), a key enzyme in the biosynthesis of estrogen, has been associated with breast cancer risk, but most previous studies have been relatively small.
We genotyped 1,544 incident cases of primary breast cancer and 1,502 population controls, all postmenopausal Swedish women, for the CYP17 c.1-34T>C polymorphism and calculated odds ratios (ORs) and 95% confidence intervals (CIs) from logistic regression models.
No overall association was found between CYP17 c.1-34T>C and breast cancer risk, OR 1.0 (95% CI 0.8-1.3) for the A2/A2 (CC) carriers compared to the A1/A1 (TT) carriers, regardless of histopathology. We detected an interaction between CYP17 c.1-34T>C and age at menarche (P = 0.026) but regarded that as a chance finding as no dose-response pattern was evident. Other breast cancer risk factors, including menopausal hormone use and diabetes mellitus, did not modify the overall results.
It is unlikely that CYP17 c.1-34T>C has a role in breast cancer etiology, overall or in combination with established non-genetic breast cancer risk factors.
细胞色素P450c17(CYP17)是雌激素生物合成中的关键酶,其c.1-34T>C 5'启动子区域多态性与乳腺癌风险相关,但此前大多数研究规模相对较小。
我们对1544例原发性乳腺癌初发病例和1502名人群对照(均为瑞典绝经后女性)进行CYP17 c.1-34T>C多态性基因分型,并通过逻辑回归模型计算比值比(OR)和95%置信区间(CI)。
无论组织病理学如何,与A1/A1(TT)携带者相比,A2/A2(CC)携带者中未发现CYP17 c.1-34T>C与乳腺癌风险之间存在总体关联,OR为1.0(95%CI 0.8-1.3)。我们检测到CYP17 c.1-34T>C与初潮年龄之间存在相互作用(P = 0.026),但由于未发现明显的剂量反应模式,将其视为偶然发现。其他乳腺癌风险因素,包括绝经后激素使用和糖尿病,并未改变总体结果。
CYP17 c.1-34T>C在乳腺癌病因中总体上或与已确定的非遗传乳腺癌风险因素联合作用时,不太可能发挥作用。