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  • Online-Ressource  (6)
  • Ergas, Isaac J.  (6)
  • Yao, Song  (6)
  • 1
    In: npj Breast Cancer, Springer Science and Business Media LLC, Vol. 8, No. 1 ( 2022-03-23)
    Kurzfassung: Few germline genetic variants have been robustly linked with breast cancer outcomes. We conducted trans-ethnic meta genome-wide association study (GWAS) of overall survival (OS) in 3973 breast cancer patients from the Pathways Study, one of the largest prospective breast cancer survivor cohorts. A locus spanning the UACA gene, a key regulator of tumor suppressor Par-4, was associated with OS in patients taking Par-4 dependent chemotherapies, including anthracyclines and anti-HER2 therapy, at a genome-wide significance level ( $$P = 1.27 \times 10^{ - 9}$$ P = 1.27 × 1 0 − 9 ). This association was confirmed in meta-analysis across four independent prospective breast cancer cohorts (combined hazard ratio = 1.84, $$P = 1.28 \times 10^{ - 11}$$ P = 1.28 × 1 0 − 11 ). Transcriptome-wide association study revealed higher UACA gene expression was significantly associated with worse OS ( $$P = 4.68 \times 10^{ - 7}$$ P = 4.68 × 1 0 − 7 ). Our study identified the UACA locus as a genetic predictor of patient outcome following treatment with anthracyclines and/or anti-HER2 therapy, which may have clinical utility in formulating appropriate treatment strategies for breast cancer patients based on their genetic makeup.
    Materialart: Online-Ressource
    ISSN: 2374-4677
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2022
    ZDB Id: 2843288-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    In: Cancer Research Communications, American Association for Cancer Research (AACR), Vol. 3, No. 6 ( 2023-06-22), p. 1104-1112
    Kurzfassung: Previous studies suggest associations of metabolic syndromes with breast cancer prognosis, yet the evidence is mixed. In recent years, the maturation of genome-wide association study findings has led to the development of polygenic scores (PGS) for many common traits, making it feasible to use Mendelian randomization to examine associations between metabolic traits and breast cancer outcomes. In the Pathways Study of 3,902 patients and a median follow-up time of 10.5 years, we adapted a Mendelian randomization approach to calculate PGS for 55 metabolic traits and tested their associations with seven survival outcomes. Multivariable Cox proportional hazards models were used to derive HRs and 95% confidence intervals (CI) with adjustment for covariates. The highest tertile (T3) of PGS for cardiovascular disease was associated with shorter overall survival (HR = 1.34, 95% CI = 1.11–1.61) and second primary cancer–free survival (HR = 1.31, 95% CI = 1.12–1.53). PGS for hypertension (T3) was associated with shorter overall survival (HR = 1.20, 95% CI = 1.00–1.43), second primary cancer–free survival (HR = 1.24, 95% CI = 1.06–1.45), invasive disease-free survival (HR = 1.18, 95% CI = 1.01–1.38), and disease-free survival (HR = 1.21, 95% CI = 1.04–1.39). PGS for serum cystatin C levels (T3) was associated with longer disease-free survival (HR = 0.82, 95% CI = 0.71–0.95), breast event-free survival (HR = 0.74, 95% CI = 0.61–0.91), and breast cancer–specific survival (HR = 0.72, 95% CI = 0.54–0.95). The above associations were significant at a nominal P & lt; 0.05 level but not after correcting for multiple testing (Bonferroni P & lt; 0.0009). Our analyses revealed notable associations of PGS for cardiovascular disease, hypertension, and cystatin C levels with breast cancer survival outcomes. These findings implicate metabolic traits in breast cancer prognosis. Significance: To our knowledge, this is the largest study of PGS for metabolic traits with breast cancer prognosis. The findings revealed significant associations of PGS for cardiovascular disease, hypertension, and cystatin C levels with several breast cancer survival outcomes. These findings implicate an underappreciated role of metabolic traits in breast cancer prognosis that would warrant further exploration.
    Materialart: Online-Ressource
    ISSN: 2767-9764
    Sprache: Englisch
    Verlag: American Association for Cancer Research (AACR)
    Publikationsdatum: 2023
    ZDB Id: 3098144-X
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 10510-10510
    Kurzfassung: 10510 Background: There have been suggestive findings for better cancer survival with vitamin D supplementation in the recent VITAL trial. The findings are consistent with meta-analyses based on earlier randomized trials testing daily supplement vitamin D intake. As there is no ongoing or planned randomized trial of vitamin D supplementation in sight for women after breast cancer diagnosis, we evaluated relationships between serum levels of vitamin D and breast cancer outcomes in a large prospective cohort of breast cancer survivors. Methods: We measured 25-hydroxyvitamin D (25OHD) levels in serum samples collected at the time of diagnosis from 3,995 women with incident breast cancer enrolled in the Pathways Study, a large prospective cohort established in 2006 at Kaiser Permanente Northern California with active follow-up (FU). Potential determinants of 25OHD levels, including a polygenic score, were examined. Vitamin D levels were categorized based on clinical cutoffs as deficient ( 〈 20 ng/ml), insufficient (20 to 〈 30 ng/ml), or sufficient (≥30 ng/ml). These levels were then evaluated in relation to overall survival (OS), breast cancer-specific survival (BCSS), recurrence-free survival (RFS), and invasive disease-free survival (IDFS). Cox proportional hazards models were adjusted for non-clinical, clinical, and treatment factors and were further stratified by stage, estrogen receptor (ER) status, and body mass index (BMI). Results: Vitamin D supplement use, lower BMI, and self-reported white race were the strongest determinants of higher 25OHD levels. The polygenic score was significantly associated with 25OHD levels but explained only 0.3% of the variance. The median FU was 9.6 years (range: 0.3-13). Compared to those with deficient vitamin D levels, patients with sufficient levels had significantly better survival outcomes, which remained after controlling for various covariates (OS: HR [95% CI] = 0.73 [0.58-0.91]; BCSS: HR = 0.78 [0.56-1.09] ; RFS: HR = 0.79 [0.65-0.97]; IDFS: HR = 0.82 [0.68-0.99] ). Associations were similar by ER status, but stronger among patients with more advanced stage disease and those with under-weight or normal BMI. Black patients had the lowest 25OHD levels, which contributed to their poorer survival compared to white patients. Adding 25OHD levels to the Cox model of OS lowered the HR associated with Black vs. white race from 2.03 (1.57-2.62) to 1.79 (1.37-2.32). Conclusions: Sufficient vitamin D levels at the time of diagnosis were associated with improved breast cancer prognosis. Consistent with results from randomized trials, our findings from a large observational cohort of breast cancer survivors with long FU provide the strongest evidence to date for maintaining sufficient vitamin D levels in breast cancer patients, including among Black women and those with more advanced stage disease.
    Materialart: Online-Ressource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Clinical Oncology (ASCO)
    Publikationsdatum: 2021
    ZDB Id: 2005181-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
    In: Clinical Breast Cancer, Elsevier BV, Vol. 19, No. 4 ( 2019-08), p. 225-235.e2
    Materialart: Online-Ressource
    ISSN: 1526-8209
    Sprache: Englisch
    Verlag: Elsevier BV
    Publikationsdatum: 2019
    ZDB Id: 2175989-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
    In: Breast Cancer Research and Treatment, Springer Science and Business Media LLC, Vol. 159, No. 1 ( 2016-8), p. 119-129
    Materialart: Online-Ressource
    ISSN: 0167-6806 , 1573-7217
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2016
    ZDB Id: 2004077-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 24, No. 8 ( 2015-08-01), p. 1207-1213
    Kurzfassung: Background: Whole-exome sequencing (WES) has recently emerged as an appealing approach to systematically study coding variants. However, the requirement for a large amount of high-quality DNA poses a barrier that may limit its application in large cancer epidemiologic studies. We evaluated the performance of WES with low input amount and saliva DNA as an alternative source material. Methods: Five breast cancer patients were randomly selected from the Pathways Study. From each patient, four samples, including 3 μg, 1 μg, and 0.2 μg blood DNA and 1 μg saliva DNA, were aliquoted for library preparation using the Agilent SureSelect Kit and sequencing using Illumina HiSeq2500. Quality metrics of sequencing and variant calling, as well as concordance of variant calls from the whole exome and 21 known breast cancer genes, were assessed by input amount and DNA source. Results: There was little difference by input amount or DNA source on the quality of sequencing and variant calling. The concordance rate was about 98% for single-nucleotide variant calls and 83% to 86% for short insertion/deletion calls. For the 21 known breast cancer genes, WES based on low input amount and saliva DNA identified the same set variants in samples from a same patient. Conclusions: Low DNA input amount, as well as saliva DNA, can be used to generate WES data of satisfactory quality. Impact: Our findings support the expansion of WES applications in cancer epidemiologic studies where only low DNA amount or saliva samples are available. Cancer Epidemiol Biomarkers Prev; 24(8); 1207–13. ©2015 AACR.
    Materialart: Online-Ressource
    ISSN: 1055-9965 , 1538-7755
    Sprache: Englisch
    Verlag: American Association for Cancer Research (AACR)
    Publikationsdatum: 2015
    ZDB Id: 2036781-8
    ZDB Id: 1153420-5
    Standort Signatur Einschränkungen Verfügbarkeit
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