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  • 1
    In: Journal of the National Cancer Institute, Oxford University Press (OUP), Vol. 107, No. 11 ( 2015-11), p. djv219-
    Type of Medium: Online Resource
    ISSN: 0027-8874 , 1460-2105
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2015
    detail.hit.zdb_id: 2992-0
    detail.hit.zdb_id: 1465951-7
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  • 2
    In: International Journal of Epidemiology, Oxford University Press (OUP), Vol. 49, No. 4 ( 2020-08-01), p. 1117-1131
    Abstract: Conventional epidemiologic studies have evaluated associations between circulating lipid levels and breast cancer risk, but results have been inconsistent. As Mendelian randomization analyses may provide evidence for causal inference, we sought to evaluate potentially unbiased associations between breast cancer risk and four genetically predicted lipid traits. Methods Previous genome-wide association studies (GWAS) have identified 164 discrete variants associated with high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), triglycerides and total cholesterol. We used 162 of these unique variants to construct weighted genetic scores (wGSs) for a total of 101 424 breast cancer cases and 80 253 controls of European ancestry from the Breast Cancer Association Consortium (BCAC). Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between per standard deviation increase in genetically predicted lipid traits and breast cancer risk. Additional Mendelian randomization analysis approaches and sensitivity analyses were conducted to assess pleiotropy and instrument validity. Results Corresponding to approximately 15 mg/dL, one standard deviation increase in genetically predicted HDL-C was associated with a 12% increased breast cancer risk (OR: 1.12, 95% CI: 1.08–1.16). Findings were consistent after adjustment for breast cancer risk factors and were robust in several sensitivity analyses. Associations with genetically predicted triglycerides and total cholesterol were inconsistent, and no association for genetically predicted LDL-C was observed. Conclusions This study provides strong evidence that circulating HDL-C may be associated with an increased risk of breast cancer, whereas LDL-C may not be related to breast cancer risk.
    Type of Medium: Online Resource
    ISSN: 0300-5771 , 1464-3685
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 1494592-7
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  • 3
    In: Nature Genetics, Springer Science and Business Media LLC, Vol. 44, No. 3 ( 2012-3), p. 307-311
    Type of Medium: Online Resource
    ISSN: 1061-4036 , 1546-1718
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2012
    detail.hit.zdb_id: 1494946-5
    SSG: 12
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  • 4
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    Online Resource
    American Association for Cancer Research (AACR) ; 2015
    In:  Clinical Cancer Research Vol. 21, No. 16_Supplement ( 2015-08-15), p. POSTER-TECH-1103-POSTER-TECH-1103
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 21, No. 16_Supplement ( 2015-08-15), p. POSTER-TECH-1103-POSTER-TECH-1103
    Abstract: Background: Extensive literature indicates that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) are associated with reduced cancer incidence and mortality. For ovarian cancer, a pooled analysis of 12 case-control studies recently demonstrated a significantly reduced risk for regular aspirin use and a similar but non-significant reduced risk for non-aspirin NSAID use. However, studies specifically evaluating NSAIDs and ovarian cancer survival are absent from the published literature. Purpose: To determine if aspirin and other NSAIDs are associated with ovarian cancer survival. Methods: Ovarian cancer cases were identified from de-identified electronic medical records (EMR) from the Vanderbilt University Medical Center. Ever use of aspirin or any NSAID was determined by MedEx, a natural language processing system designed to capture medication use from EMR. Linked tumor registry data was used to generate hazard ratios (HR) and confidence intervals (CI) for overall survival using Cox proportional hazards regression; covariates included age, race, stage of disease, histologic subtype, treatments received, and year of diagnosis. Results: The majority of 1,147 confirmed ovarian cancer cases were Caucasian (87.0%), had serous histologic subtypes (53.6%), and late stage (III/IV, 50.0%) or stage unknown (29.3%) disease. Ovarian cancer cases with any aspirin use (207, 18.1%) had significantly longer overall survival in both unadjusted (HR: 0.56, 95% CI: 0.45-0.70) and adjusted analyses (HR: 0.59, 95% CI: 0.46-0.74). Similarly, ovarian cancer cases with any non-aspirin NSAID use (248, 21.6%) had significantly longer overall survival in both unadjusted (HR: 0.60, 95% CI: 0.48-0.74) and adjusted analyses (HR: 0.69, 95% CI: 0.54-0.88). Associations between any aspirin or other NSAID use (360, 31.4%) and longer ovarian cancer survival did not significantly differ by stage of disease (P-interaction=0.650), histologic subtype (P-interaction=0.076), or treatment with a platinum-based agent (P-interaction=0.069). Conclusions: Indication of aspirin or non-aspirin NSAID use ascertained retrospectively from EMR was associated with improved overall ovarian cancer survival. Further evaluation, including timing and duration of use, are underway; replication of this association in additional study populations is needed. Citation Format: Alicia Beeghly-Fadiel, Gwendolyn Holman, Samantha P. Stansel, Gretchen Edwards, Edward Baeg, Hannah Berke, Ryan J. Delahanty, Dineo Khabele. Aspirin, NSAIDS, and ovarian cancer survival from electronic medical records [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-TECH-1103.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
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    detail.hit.zdb_id: 2036787-9
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  • 5
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 22, No. 2 ( 2013-02-01), p. 216-223
    Abstract: Background: Experimental and epidemiologic evidence have suggested that chronic inflammation may play a critical role in endometrial carcinogenesis. Methods: To investigate this hypothesis, a two-stage study was carried out to evaluate single-nucleotide polymorphisms (SNP) in inflammatory pathway genes in association with endometrial cancer risk. In stage I, 64 candidate pathway genes were identified and 4,542 directly genotyped or imputed SNPs were analyzed among 832 endometrial cancer cases and 2,049 controls, using data from the Shanghai Endometrial Cancer Genetics Study. Linkage disequilibrium of stage I SNPs significantly associated with endometrial cancer (P & lt; 0.05) indicated that the majority of associations could be linked to one of 24 distinct loci. One SNP from each of the 24 loci was then selected for follow-up genotyping. Of these, 21 SNPs were successfully designed and genotyped in stage II, which consisted of 10 additional studies including 6,604 endometrial cancer cases and 8,511 controls. Results: Five of the 21 SNPs had significant allelic odds ratios (ORs) and 95% confidence intervals (CI) as follows: FABP1, 0.92 (0.85–0.99); CXCL3, 1.16 (1.05–1.29); IL6, 1.08 (1.00–1.17); MSR1, 0.90 (0.82–0.98); and MMP9, 0.91 (0.87–0.97). Two of these polymorphisms were independently significant in the replication sample (rs352038 in CXCL3 and rs3918249 in MMP9). The association for the MMP9 polymorphism remained significant after Bonferroni correction and showed a significant association with endometrial cancer in both Asian- and European-ancestry samples. Conclusions: These findings lend support to the hypothesis that genetic polymorphisms in genes involved in the inflammatory pathway may contribute to genetic susceptibility to endometrial cancer. Impact statement: This study adds to the growing evidence that inflammation plays an important role in endometrial carcinogenesis. Cancer Epidemiol Biomarkers Prev; 22(2); 216–23. ©2012 AACR.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2013
    detail.hit.zdb_id: 2036781-8
    detail.hit.zdb_id: 1153420-5
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  • 6
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2013
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 22, No. 3 ( 2013-03-01), p. 467-469
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 22, No. 3 ( 2013-03-01), p. 467-469
    Abstract: Background: As breast and ovarian cancers may have similar etiologies, this study aimed to evaluate the hypothesis that breast cancer shares common genetic susceptibility variants with ovarian cancer. Methods: Ten genetic variants in nine loci were previously identified to be associated with ovarian cancer risk among Caucasian women; an additional 353 variants in high-linkage disequilibrium (r2 ≥ 0.6) among Han Chinese were identified. Data were available from the Affymetrix Genome-Wide Array (6.0) or MACH imputation for 25 and 78 common genetic variants [minor allele frequency (MAF) ≥0.05], respectively. Associations with breast cancer risk were evaluated by additive logistic regression models among 2,918 breast cancer cases and 2,324 controls. Results: No associations with breast cancer risk were evident for 103 ovarian cancer susceptibility variants in five loci. Four loci were not evaluated, as they included only rare variants (MAF & lt; 0.05). Conclusions: Ovarian cancer susceptibility variants identified in Caucasian women were not associated with breast cancer risk among 5,242 Chinese women. Impact: These findings suggest that breast and ovarian cancer may not share common susceptibility variants among Chinese women. Cancer Epidemiol Biomarkers Prev; 22(3); 467–9. ©2013 AACR.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2013
    detail.hit.zdb_id: 2036781-8
    detail.hit.zdb_id: 1153420-5
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  • 7
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2011
    In:  Cancer Research Vol. 71, No. 8_Supplement ( 2011-04-15), p. LB-444-LB-444
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. LB-444-LB-444
    Abstract: Aberrant transforming growth factor-beta (TGFB) signaling contributes to tumor progression. To clarify the role of TGFB pathway variants and breast cancer survival, we conducted a two stage study among 4,535 breast cancer patients recruited in two studies conducted in Shanghai, China. In Stage I, 111 variants in TGFB, TGFBR1, and TGFBR2 were evaluated for associations with disease-free (DFS) and overall survival (OS) among 2,923 participants with a median of 5.5 years of follow-up time after their cancer diagnosis. Nominally significant associations with either DFS or OS were found for 31 variants, which after considering linkage disequilibrium, were found to represent 13 independent loci. Stage II genotyping was conducted among 1,612 additional participants with a median follow-up time of 5.1 years; data was available for 11 loci. Genetic variants in 6 loci were not associated with breast cancer outcomes in Stage II. Variants in 4 loci showed associations in Stage II that were generally consistent, but did not reach statistical significance. One variant was significantly associated with overall breast cancer survival in both study stages, and overall and disease free survival in analyses of the two study stage samples combined. Specifically, women with two copies of the rare variant of TGFBR1 rs3773651 (GG) had increased hazards of recurrence or breast cancer specific mortality (HR: 2.05, 95% CI: 1.28–3.27) and overall mortality (HR: 2.44, 95% CI: 1.50–3.95) compared to women with one or more common alleles (AG, AA) in age adjusted analyses. Additional adjustment for disease stage, ER, PR, or treatment including surgery, chemotherapy, radiotherapy, and tamoxifen did not attenuate these effects. Further, the statistical significance of these associations was retained after consideration was made for multiple comparisons (DFS p-value 0.0027; OS p-value 0.0003). rs3773651 is located in intron six of TGFBR2, a TGFB ligand specific receptor critical for transduction of TGFB signaling. Our data support a role for individual variation in TGFBR2 in breast cancer survival outcomes; additional investigation is warranted. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-444. doi:10.1158/1538-7445.AM2011-LB-444
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 8
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. LB-331-LB-331
    Abstract: Experimental and epidemiological evidence have suggested that chronic inflammation may play a critical role in endometrial carcinogenesis. To investigate this hypothesis, we carried out a two-stage study to evaluate single nucleotide polymorphisms (SNPs) in inflammatory pathway genes in association with endometrial cancer risk. In stage 1, 64 candidate pathway genes were identified and 4,542 directly genotyped or imputed SNPs were analyzed among 830 endometrial cancer cases and 2,322 controls using data from the Shanghai Endometrial Cancer Genetics Study. Linkage disequilibrium of stage 1 SNPs significantly associated with endometrial cancer (P & lt;0.05) indicated that the majority of associations could be linked to one of 24 distinct loci. We then selected one SNP from each of the 24 loci for follow-up genotyping. Of these, 21 SNPs were successfully designed and genotyped in the stage 2 sample, which consisted of eight additional studies including 4,890 endometrial cancer cases and 5,403 controls. Four of the 21 SNPs in or near the FABP1, CXCL3, MSR1, and MMP9 genes were significantly associated with endometrial cancer in the combined data sets. The allelic odds ratios were 0.90 (0.82-0.97) for FABP1, 1.17 (1.05-1.31) for CXCL3, 0.86 (0.78-0.96) for MSR1, and 0.90 (0.85-0.95) for MMP9. The SNPs in CXCL3 and MMP9 were significantly associated with endometrial cancer in both the discovery and replication samples. Of these findings, the association for the MMP9 promoter polymorphism rs3918249 (P=0.00047) remained significant after adjustment for the total number of comparisons. These findings suggest that genetic polymorphisms in the MMP9 gene and possibly in or near the FABP1, CXCL3, and MSR1 genes may contribute to genetic susceptibility to endometrial cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-331. doi:1538-7445.AM2012-LB-331
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 9
    Online Resource
    Online Resource
    Elsevier BV ; 2019
    In:  Annals of Emergency Medicine Vol. 73, No. 4 ( 2019-04), p. 334-344
    In: Annals of Emergency Medicine, Elsevier BV, Vol. 73, No. 4 ( 2019-04), p. 334-344
    Type of Medium: Online Resource
    ISSN: 0196-0644
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2019
    detail.hit.zdb_id: 2003465-9
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  • 10
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  Critical Care Medicine Vol. 46, No. 6 ( 2018-06), p. e481-e488
    In: Critical Care Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 46, No. 6 ( 2018-06), p. e481-e488
    Abstract: Risk adjustment algorithms for ICU mortality are necessary for measuring and improving ICU performance. Existing risk adjustment algorithms are not widely adopted. Key barriers to adoption include licensing and implementation costs as well as labor costs associated with human-intensive data collection. Widespread adoption of electronic health records makes automated risk adjustment feasible. Using modern machine learning methods and open source tools, we developed and evaluated a retrospective risk adjustment algorithm for in-hospital mortality among ICU patients. The Risk of Inpatient Death score can be fully automated and is reliant upon data elements that are generated in the course of usual hospital processes. Setting: One hundred thirty-one ICUs in 53 hospitals operated by Tenet Healthcare. Patients: A cohort of 237,173 ICU patients discharged between January 2014 and December 2016. Design: The data were randomly split into training (36 hospitals), and validation (17 hospitals) data sets. Feature selection and model training were carried out using the training set while the discrimination, calibration, and accuracy of the model were assessed in the validation data set. Measurements and Main Results: Model discrimination was evaluated based on the area under receiver operating characteristic curve; accuracy and calibration were assessed via adjusted Brier scores and visual analysis of calibration curves. Seventeen features, including a mix of clinical and administrative data elements, were retained in the final model. The Risk of Inpatient Death score demonstrated excellent discrimination (area under receiver operating characteristic curve = 0.94) and calibration (adjusted Brier score = 52.8%) in the validation dataset; these results compare favorably to the published performance statistics for the most commonly used mortality risk adjustment algorithms. Conclusions: Low adoption of ICU mortality risk adjustment algorithms impedes progress toward increasing the value of the healthcare delivered in ICUs. The Risk of Inpatient Death score has many attractive attributes that address the key barriers to adoption of ICU risk adjustment algorithms and performs comparably to existing human-intensive algorithms. Automated risk adjustment algorithms have the potential to obviate known barriers to adoption such as cost-prohibitive licensing fees and significant direct labor costs. Further evaluation is needed to ensure that the level of performance observed in this study could be achieved at independent sites.
    Type of Medium: Online Resource
    ISSN: 0090-3493
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
    detail.hit.zdb_id: 2034247-0
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