ABSTRACT. Coronary heart disease (CHD) has become a leading cause of human deaths worldwide. Recent studied showed that polymorphisms of the matrix metalloproteinase (MMP) genes played important roles in extracellular matrix remodeling and contribute to the pathogenesis of vascular diseases. Here, we investigated whether these MMP gene polymorphisms were associated with CHD in Han Chinese. Our case-control study was involved with 1509 unrelated individuals, 12255Matrix metalloproteinases and coronary heart disease ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 12254-12261 (2015) including 777 CHD cases and 732 controls. We selected a total of five polymorphisms whose genotypes were determined using Sequenom iPLEX technology. Our results showed there were no significant associations between the five MMP gene polymorphisms and CHD risk at either genotype or allele levels (P > 0.05). Further subgroup analyses by sex were also unable to reveal any significant association (P > 0.05).In conclusion, no significant associations were found between the five MMP gene polymorphisms and the risk of CHD in Han Chinese.
Long-term low-dose aspirin use has been observed to reduce the risk of colorectal, breast and other cancers. The most prominent effect has been in colorectal cancer, in which large-scale meta-analyses have shown that there is an approximately 20% relative risk reduction in participants who took aspirin for four or more years. The role of long-term NSAID use in breast cancer risk is less clear although preliminary observational case-control studies suggest an association between aspirin use and reduced incidence of hormone receptor-positive breast cancers though no clear evidence exists to support a clear mortality benefit among patients with a history of prior NSAID use as opposed to those who do not. To investigate whether a history of aspirin use is associated with improved clinical outcome in breast cancer, we examined the pattern of aspirin use, cancer pathology and overall survival of over 1000 patients diagnosed with and treated for invasive breast cancer at our institution, for whom long-term follow up was available. A history of aspirin use for at least a period of 30 days prior to breast cancer diagnosis was reported in nearly 14% of individuals. Aspirin use was associated with being older than the age of 50 at diagnosis (79.8% vs 66.5%; Fisher's Exact Test (P < 3.2x10-3) and being of African American race (49.1% vs 28.7%; P < 3.4x10-2), when compared to those who have not used aspirin. Aspirin use correlated with prognostic factors that are known to be associated with poor outcomes. They include axilla node positive disease (44.5% vs 27.0%, p< 0.032), evidence of lymphovascular invasion (24.7% vs 15.4%, p< 0.049), Her2-neu positive disease (<0.0083). In contrast to prior retrospective case-control studies, no significant association between aspirin use and hormone receptor positive disease was noted for either ER (p=0.19) or PR(+) receptor status (p=0.12). Finally, we examined if aspirin use prior to breast cancer diagnosis has any impact on disease outcome. Over a median follow up of 60.0 months, univariate analysis using cox proportional hazard modeling demonstrated that the use of low-dose aspirin prior to the diagnosis of breast cancer was associated with an increased all-cause mortality when compared to patients without aspirin use prior to cancer diagnosis (HR=3.084, 95% CI=1.961 to 4.848). On multivariate analysis, we found that recent history of aspirin use was significantly associated with a worse overall survival (HR 2.65; 95%CI 1.37 -5.12, P < 3.77 x 10-3), when controlled for other prognostic factors including receptor status, tumor size, tumor grade, number of positive regional lymph nodes, positive margins, as well as race and age at diagnosis. This is the first study to report on the association of aspirin use with breast cancer outcomes in a large patient cohort treated at a single institution. Although aspirin in breast and cancers has been associated with reduced cancer incidence, a history of aspirin use prior to breast cancer diagnosis does not appear to be protective or associated with improve clinical outcomes or survival among breast cancer patients. Ongoing efforts are examining the mechanism underlying this association. Citation Format: Li YR, Steel L, Carrigan E, Tchou J. Association of aspirin and clinical outcomes in patients with invasive breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr PD1-04.
This abstract was withdrawn by the authors.
Background: Long-term use of AMP-kinase agonist Metformin, the first-line oral hypoglycemic agent, has recently been shown to be associated with both a decreased incidence of and improved survival following diagnosis of breast and other solid tumors. However, the sample size of most reported studies has been limited and has not been able to clearly delineate if there are molecular subtype-dependent effects. Method: We implemented a population-based, retrospective case-control analysis of the effect of metformin on breast cancer outcomes. We comprehensively searched the electronic medical records of all female patients who were cared for within the University of Pennsylvania Health System between the years 1997 and 2013. To ensure the accuracy of patient selection, we focused our preliminary analysis on only patients (n = 20,684) who received an ICD9 code for breast cancer (BC) on at least 2 separate in-person visits. We assessed the use of metformin by identifying those patients who have at least a record of a metformin prescription both before the first breast cancer diagnosis ICD9 code and after the first breast cancer diagnosis visit. Overall survival was determined by assessing a combination of electronic medical record of patient expiration and the SSN Death Certificate Index. Statistical tests, including chi-sq and cox-hazard modeling were implemented in R, Graphpad Prism or EXCEL. Results: In the preliminary analysis, we identified a total of 29,251 female patients either diagnosed or reported a history of BC within the UPHS EMRs. Stratifying by per patient visits, we limited the subsequent analysis to the 20,684 BC patients with at least 2 in-person visits where BC was recorded as a diagnosis code. Of these, there were 534 patients who had a record of metformin prescription prior to and after the first BC diagnosis code and 20,150 BC patients who did not. We found that with a mean follow up of (6.40 years), there were a total of 8 deaths (1.28%) in metformin users and 526 deaths (2.62%) among the no metformin users. Using a two-tailed chi-sq test, we found that metformin use was significantly associated with improved overall survival rates (98.50 vs 96.94%, p<0.05). We are currently assessing the role of age, ethnicity, the presence of diabetes, health metrics related to insulin resistance, and the use of other metabolic regulators (insulin, sulfonylurea) using a cox-hazard proportional risk model. Conclusion: Our preliminary analyses suggest that metformin use before and following diagnosis may be protective against overall mortality among women diagnosed with breast cancer. A more refined Cox proportional hazard modelling is ongoing, which will shed light on how factors such as the use of other metabolic agents, age, and breast cancer subtype may interact with metformin's effect on overall and disease-free BC survival. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-06-01.
The prediction of power grid electricity is the key to ensure the reliable and economic operation of power system. In order to improve the accuracy of power grid electricity forecast, a new power grid electricity forecast model in multi-dimensional scenarios is proposed in this paper. The simulation results show that this method has higher prediction accuracy, and it provides a new idea for the research of power grid electricity prediction
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