The role of adipocytokines and insulin-like growths factors in breast carcinogenesis
| Autor: | Mei-Hsuan Wu, 吳美萱 |
|---|---|
| Rok vydání: | 2009 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 98 Obesity is a well-known risk factor for breast cancer. Mechanisms linking obesity with breast cancer risk might through three possible pathways, including the insulin and insulin-like growth factor (IGF-I) axis, estrogen exposure, and adipokines. It has been noted that leptin stimulates estrogen synthesis by upregulation of aromatase activity and activates proliferation and cell survival; while, adiponectin inhibits proliferation in mammary epithelial cells. The imbalance of adiponectin and leptin activities could reduce the insulin sensitivity of peripheral tissues and induce insulin resistance. Insulin-like growth factor I (IGF-I) is a mitogen for mammary epithelial cells. In the obesity and insulin resistance status, increased bioavailability of IGF-I and the crosstalk between IGF-I and estrogen could induce estrogen receptor expression and progress the cell cycle from G1 to S phase. Taken together, these potential mechanisms may contribute to breast carcinogenesis. Therefor, the present study using hospital -based case-control study design aimed to evaluate the potential associations between anthropometric measures, circulating plasma levels of adiponectin, leptin, and IGF-I and breast cancer risk. In particular, the current study assessed the potential mechanisms for obesity-related breast carcinogenesis between premenopausal and postmenopausal women. The present hospital-based case-control study was conducted at Tri-Service General Hospital, Taipei from 2004 to 2006, with a total of 297 pathologically confirmed incidence breast cancers and age, date of enrollment, and fasting status-matched controls (n=593). Questionnaire information, anthropometric measures, and blood specimens were taken before treatment from cases and matched controls. Plasma levels of adiponectin, leptin, and IGF-I were measured by RIA and IRMA. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for assessing associations. Overall, study results showed that a negative association between plasma adiponectin levels and breast cancer risk was observed, especially in postmenopausal breast cancer, while a positive association between plasma leptin concentrations and breast cancer was demonstrated in postmenopausal women. More interestingly, elevated IGF-I concentrations in conjunction with prolonged interval of critical period of estrogen exposure, as defined by the duration between age at menarche and age at first full-term pregnancy, were associated with significantly increased risk of breast cancer, especially in ER(+) breast cancers. In conclusion, circulating levels of adiponectin, leptin, and IGF-I may have etiologic roles in breast carcinogenesis, independent of obesity effects. In particular, IGF-I may cross-talk with estrogens to increase premenopausal breast cancer risk, while central obesity and adipokines may contribute to breast cancer risk among postmenopausal women. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
| Externí odkaz: |
|