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Article ; Online: Mediation analysis using incomplete information from publicly available data sources.

Derkach, Andriy / Kantor, Elizabeth D / Sampson, Joshua N / Pfeiffer, Ruth M

2024

Abstract: Our work was motivated by the question whether, and to what extent, well-established risk factors mediate the racial disparity observed for colorectal cancer (CRC) incidence in the United States. Mediation analysis examines the relationships between an ... ...

Abstract	Our work was motivated by the question whether, and to what extent, well-established risk factors mediate the racial disparity observed for colorectal cancer (CRC) incidence in the United States. Mediation analysis examines the relationships between an exposure, a mediator and an outcome. All available methods require access to a single complete data set with these three variables. However, because population-based studies usually include few non-White participants, these approaches have limited utility in answering our motivating question. Recently, we developed novel methods to integrate several data sets with incomplete information for mediation analysis. These methods have two limitations: (i) they only consider a single mediator and (ii) they require a data set containing individual-level data on the mediator and exposure (and possibly confounders) obtained by independent and identically distributed sampling from the target population. Here, we propose a new method for mediation analysis with several different data sets that accommodates complex survey and registry data, and allows for multiple mediators. The proposed approach yields unbiased causal effects estimates and confidence intervals with nominal coverage in simulations. We apply our method to data from U.S. cancer registries, a U.S.-population-representative survey and summary level odds-ratio estimates, to rigorously evaluate what proportion of the difference in CRC risk between non-Hispanic Whites and Blacks is mediated by three potentially modifiable risk factors (CRC screening history, body mass index, and regular aspirin use).
Language	English
Publishing date	2024-04-12
Publishing country	England
Document type	Journal Article
ZDB-ID	843037-8
ISSN	1097-0258 ; 0277-6715
ISSN (online)	1097-0258
ISSN	0277-6715
DOI	10.1002/sim.10076
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Article ; Online: Immune-related conditions and cancer-specific mortality among older adults with cancer in the United States.

Wang, Jeanny H / Derkach, Andriy / Pfeiffer, Ruth M / Engels, Eric A

International journal of cancer

2022 Volume 151, Issue 8, Page(s) 1216–1227

Abstract: Immunity may play a role in preventing cancer progression. We studied associations of immune-related conditions with cancer-specific mortality among older adults in the United States. We evaluated 1 229 443 patients diagnosed with 20 common cancer types ( ...

Abstract	Immunity may play a role in preventing cancer progression. We studied associations of immune-related conditions with cancer-specific mortality among older adults in the United States. We evaluated 1 229 443 patients diagnosed with 20 common cancer types (age 67-99, years 1993-2013) using Surveillance Epidemiology and End Results-Medicare data. With Medicare claims, we ascertained immune-related medical conditions diagnosed before cancer diagnosis (4 immunosuppressive conditions [n = 3380 affected cases], 32 autoimmune conditions [n = 155 766], 3 allergic conditions [n = 101 366]). For each cancer site, we estimated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for cancer-specific mortality associated with each condition, applying a Bonferroni cutoff for significance (P < 5.1 × 10
MeSH term(s)	Aged ; Aged, 80 and over ; Autoimmune Diseases/epidemiology ; Bayes Theorem ; Case-Control Studies ; Humans ; Hypersensitivity/complications ; Hypersensitivity/epidemiology ; Male ; Medicare ; Neoplasms ; SEER Program ; United States/epidemiology
Language	English
Publishing date	2022-06-23
Publishing country	United States
Document type	Journal Article ; Meta-Analysis ; Research Support, N.I.H., Intramural
ZDB-ID	218257-9
ISSN	1097-0215 ; 0020-7136
ISSN (online)	1097-0215
ISSN	0020-7136
DOI	10.1002/ijc.34140
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Zs.A 478: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Subset testing and analysis of multiple phenotypes.

Derkach, Andriy / Pfeiffer, Ruth M

Genetic epidemiology

2019 Volume 43, Issue 5, Page(s) 492–505

Abstract: Meta-analysis of multiple genome-wide association studies (GWAS) is effective for detecting single- or multimarker associations with complex traits. We develop a flexible procedure (subset testing and analysis of multiple phenotypes [STAMP]) based on ... ...

Abstract	Meta-analysis of multiple genome-wide association studies (GWAS) is effective for detecting single- or multimarker associations with complex traits. We develop a flexible procedure (subset testing and analysis of multiple phenotypes [STAMP]) based on mixture models to perform a region-based meta-analysis of different phenotypes using data from different GWAS and identify subsets of associated phenotypes. Our model framework helps distinguish true associations from between-study heterogeneity. As a measure of association, we compute for each phenotype the posterior probability that the genetic region under investigation is truly associated. Extensive simulations show that STAMP is more powerful than standard approaches for meta-analyses when the proportion of truly associated outcomes is between 25% and 50%. For other settings, the power of STAMP is similar to that of existing methods. We illustrate our method on two examples, the association of a region on chromosome 9p21 with the risk of 14 cancers, and the associations of expression of quantitative trait loci from two genetic regions with their cis-single-nucleotide polymorphisms measured in 17 tissue types using data from The Cancer Genome Atlas.
MeSH term(s)	Case-Control Studies ; Computer Simulation ; Genome-Wide Association Study/methods ; Humans ; Models, Genetic ; Neoplasms/pathology ; Phenotype ; Polymorphism, Single Nucleotide/genetics ; Quantitative Trait Loci/genetics
Language	English
Publishing date	2019-03-28
Publishing country	United States
Document type	Journal Article ; Meta-Analysis
ZDB-ID	605785-8
ISSN	1098-2272 ; 0741-0395
ISSN (online)	1098-2272
ISSN	0741-0395
DOI	10.1002/gepi.22199
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Article ; Online: Associations Between Autoimmune Conditions and Gastric Cancer Risk Among Elderly Adults in the United States.

Song, Minkyo / Camargo, M Constanza / Derkach, Andriy / Rabkin, Charles S / Engels, Eric A

The American journal of gastroenterology

2022 Volume 117, Issue 3, Page(s) 486–490

Abstract: Introduction: Pernicious anemia (PA) is a risk factor for gastric cancer. Other autoimmune conditions may also contribute.: Methods: In a case-control study, we evaluated 47 autoimmune conditions among 39,125 gastric cancers and 200,000 cancer-free ... ...

Abstract	Introduction: Pernicious anemia (PA) is a risk factor for gastric cancer. Other autoimmune conditions may also contribute. Methods: In a case-control study, we evaluated 47 autoimmune conditions among 39,125 gastric cancers and 200,000 cancer-free controls. Results: Six conditions were associated with increased gastric cancer risk (range of adjusted odds ratios: 1.28-1.93, P < 0.05): PA, membranous nephropathy, primary biliary cirrhosis, pure red cell aplasia, primary sclerosing cholangitis, and Graves disease. PA was associated with 8 other autoimmune conditions (adjusted odds ratios: 1.57-4.54, P < 0.05). Discussion: Autoimmune conditions associated with gastric cancer or PA may reflect effects of autoimmune gastritis or other carcinogenic pathways.
MeSH term(s)	Adult ; Aged ; Anemia, Pernicious/complications ; Anemia, Pernicious/epidemiology ; Autoimmune Diseases/complications ; Autoimmune Diseases/epidemiology ; Case-Control Studies ; Humans ; Stomach Neoplasms/complications ; Stomach Neoplasms/etiology ; United States/epidemiology
Language	English
Publishing date	2022-01-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	390122-1
ISSN	1572-0241 ; 0002-9270
ISSN (online)	1572-0241
ISSN	0002-9270
DOI	10.14309/ajg.0000000000001622
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Article: Pre-Diagnosis Dietary Patterns and Risk of Multiple Myeloma in the NIH-AARP Diet and Health Study.

Castro, Francesca / Parikh, Richa / Eustaquio, Jelyn C / Derkach, Andriy / Joseph, Janine M / Lesokhin, Alexander M / Usmani, Saad Z / Shah, Urvi A

medRxiv : the preprint server for health sciences

2023

Abstract: Background: Despite patient interest in knowing whether diet is linked to multiple myeloma (MM), there is limited research on dietary patterns and MM risk. Two studies have assessed this risk, albeit with a small number of MM cases. The EPIC-Oxford ... ...

Abstract	Background: Despite patient interest in knowing whether diet is linked to multiple myeloma (MM), there is limited research on dietary patterns and MM risk. Two studies have assessed this risk, albeit with a small number of MM cases. The EPIC-Oxford cohort and Oxford Vegetarian study (65 MM cases) showed that fish eaters, vegetarians and vegans had significantly reduced MM risk compared to meat eaters. The Nurses' Health Study and Health Professionals Follow-up Study (478 MM cases) showed a significantly increased MM risk in men with Empirical Dietary Inflammatory Pattern. Methods: The NIH-AARP Diet and Health study is a prospective cohort of 567,169 persons who completed a food frequency questionnaire in 1995-1996 and were followed until December 2011. Healthy Eating Index-2015 (HEI-2015), Healthy Diet Score (HDS), alternate Mediterranean Diet (aMED) and healthful Plant-based Diet Index (hPDI) scores were calculated using Results: Among 392,589 participants (after exclusions), a total of 1,366 MM cases (59% males; 92% non-Hispanic whites) were identified during the follow-up period. Analysis revealed a significant association between hPDI scores and reduced MM risk (highest vs lowest quartile, HR 0.85; 95%CI 0.73-1.0; p=0.043) (Table). In sensitivity analysis (1,302 MM cases), the association was no longer significant (HR 0.87; 95%CI 0.74-1.03; p 0.09) but trended in the same direction. This may be due to small sample size, given MM is a rare disease. HEI-2015, HDS and aMED scores were not associated with MM risk. Conclusions: A healthful plant-based diet was associated with reduced MM risk in the NIH-AARP cohort. These results will help oncologists and patients make informed choices about their diet. To our knowledge, this is the largest epidemiologic study to date assessing pre-diagnosis dietary patterns and MM risk.
Language	English
Publishing date	2023-09-23
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.09.20.23295639
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Article ; Online: Routine clinical parameters and laboratory testing predict therapy-related myeloid neoplasms after treatment for breast cancer.

Petrone, Giulia / Gaulin, Charles / Derkach, Andriy / Kishtagari, Ashwin / Robson, Mark E / Parameswaran, Rekha / Stein, Eytan M

Haematologica

2023 Volume 108, Issue 1, Page(s) 161–170

Abstract: We aim to identify predictors of therapy-related myeloid neoplasms (t-MN) in patients with breast cancer (BC) and cytopenias to determine the timing of bone marrow biopsy (BMBx). Patients with BC and cytopenias who were referred for BMBx between 2002- ... ...

Abstract	We aim to identify predictors of therapy-related myeloid neoplasms (t-MN) in patients with breast cancer (BC) and cytopenias to determine the timing of bone marrow biopsy (BMBx). Patients with BC and cytopenias who were referred for BMBx between 2002-2018 were identified using the Memorial Sloan Kettering Cancer Center institutional database. Characteristics associated with the risk of t-MN were evaluated by multivariable logistic regression and included in a predictive model. The average area under the receiver operating characteristic curve (AUC) was estimated by 5-fold cross-validation. Of the 206 BC patients who underwent BMBx included in our study, 107 had t-MN. By multivariable analysis, white blood cell count 4-11 K/mcL, absolute neutrophil count (ANC) ≥1.5 K/mcL, hemoglobin ≥12.2 g/dL, red cell distribution width 11.5-14.5%, the presence of bone metastasis and a time from BC diagnosis to BMBx <15 months significantly decreased the likelihood of t-MN. The average AUC was 0.88. We stratified our cohort by bone metastasis and by findings on peripheral smear. In both the subset without bone metastasis (n=159) and in the cohort with no blasts or dysplastic cells on peripheral smear (n=96) our variables had similar effects on the risk of t-MN. Among the 47 patients with bone metastasis, an ANC ≥1.5 K/mcL was the only variable associated with a decreased risk of t-MN. Our findings show that in patients with BC and unexplained cytopenias, clinical and laboratory parameters can predict t-MN and assist clinicians in determining the timing of a BMBx.
MeSH term(s)	Humans ; Female ; Breast Neoplasms/diagnosis ; Breast Neoplasms/etiology ; Breast Neoplasms/pathology ; Biopsy ; Bone Marrow/pathology ; Bone Neoplasms ; ROC Curve
Language	English
Publishing date	2023-01-01
Publishing country	Italy
Document type	Journal Article
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2021.280437
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Article ; Online: Clonal hematopoiesis in diffuse large B-cell lymphoma: clinical impact and genetic relatedness to lymphoma and therapy-related myeloid neoplasm.

Liu, Ying / Derkach, Andriy / Lewis, Natasha / Zhu, Menglei / Zhang, Yanming / Arcila, Maria / Salles, Gilles / Dogan, Ahmet / Xiao, Wenbin

Haematologica

2023 Volume 108, Issue 3, Page(s) 917–922

MeSH term(s)	Humans ; Clonal Hematopoiesis/genetics ; Lymphoma, Large B-Cell, Diffuse/genetics ; Lymphoma, Large B-Cell, Diffuse/pathology ; Myeloproliferative Disorders ; Hematopoiesis/genetics
Language	English
Publishing date	2023-03-01
Publishing country	Italy
Document type	Research Support, Non-U.S. Gov't ; Letter ; Research Support, N.I.H., Extramural
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2022.281724
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Article ; Online: Pre-diagnosis dietary patterns and risk of multiple myeloma in the NIH-AARP diet and health study.

Castro, Francesca / Parikh, Richa / Eustaquio, Jelyn C / Derkach, Andriy / Joseph, Janine M / Lesokhin, Alexander M / Usmani, Saad Z / Shah, Urvi A

Leukemia

2023 Volume 38, Issue 2, Page(s) 438–441

MeSH term(s)	Humans ; United States/epidemiology ; Multiple Myeloma/diagnosis ; Multiple Myeloma/etiology ; Dietary Patterns ; Diet ; Risk Factors ; Proportional Hazards Models
Language	English
Publishing date	2023-12-29
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	807030-1
ISSN	1476-5551 ; 0887-6924
ISSN (online)	1476-5551
ISSN	0887-6924
DOI	10.1038/s41375-023-02132-3
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Article ; Online: Somatic mutations in FAS pathway increase hemophagocytic lymphohistiocytosis risk in T- and/or NK-cell lymphoma patients.

Liu, Ying / Sardana, Rohan / Nemirovsky, David / Frosina, Denise / Jungbluth, Achim / Johnson, William T / Vardhana, Santosha A / Arcila, Maria E / Horwitz, Steven M / Derkach, Andriy / Dogan, Ahmet / Xiao, Wenbin

Blood advances

2024

Abstract: While significant progress has been made in understanding the genetic basis of primary hemophagocytic lymphohistiocytosis (HLH), the pathogenesis of secondary HLH, the more prevalent form, remains unclear. Among the various conditions giving rise to ... ...

Abstract	While significant progress has been made in understanding the genetic basis of primary hemophagocytic lymphohistiocytosis (HLH), the pathogenesis of secondary HLH, the more prevalent form, remains unclear. Among the various conditions giving rise to secondary HLH, HLH in lymphoma patients (HLH-L) accounts for a substantial proportion. In this study, we investigated the role of somatic mutations in the pathogenesis of HLH-L in a cohort of patients with T- and/or NK-cell lymphoma. We identified a 3-time higher frequency of mutations in FAS pathway in patients with HLH-L. Patients harbouring these mutations had a 5-time increased HLH-L risk. These mutations were independently associated with inferior outcome. Hence, our study demonstrates the association between somatic mutations in FAS pathway and HLH-L. Further studies are warranted on the mechanistic role of these mutations in HLH-L.
Language	English
Publishing date	2024-04-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2023011733
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Article ; Online: Multilineage involvement in KMT2A-rearranged B acute lymphoblastic leukaemia: cell-of-origin, biology, and clinical implications.

Aypar, Umut / Dilip, Deepika / Gadde, Ramya / Londono, Dory M / Liu, Ying / Gao, Qi / Geyer, Mark B / Derkach, Andriy / Zhang, Yanming / Glass, Jacob L / Roshal, Mikhail / Xiao, Wenbin

Histopathology

2024

Abstract: Aims: B lymphoblastic leukaemia/lymphoma (B-ALL) is thought to originate from Pro/Pre-B cells and the genetic aberrations largely reside in lymphoid-committed cells. A recent study demonstrated that a proportion of paediatric B-ALL patients have BCR:: ... ...

Abstract	Aims: B lymphoblastic leukaemia/lymphoma (B-ALL) is thought to originate from Pro/Pre-B cells and the genetic aberrations largely reside in lymphoid-committed cells. A recent study demonstrated that a proportion of paediatric B-ALL patients have BCR::ABL1 fusion in myeloid cells, suggesting a chronic myeloid leukaemia (CML)-like biology in this peculiar subset of B-ALL, although it is not entirely clear if the CD19-negative precursor compartment is a source of the myeloid cells. Moreover, the observation has not yet been extended to other fusion-driven B-ALLs. Methods and results: In this study we investigated a cohort of KMT2A-rearranged B-ALL patients with a comparison to BCR::ABL1-rearranged B-ALL by performing cell sorting via flow cytometry followed by FISH (fluorescence in situ hybridization) analysis on each of the sorted populations. In addition, RNA sequencing was performed on one of the sorted populations. These analyses showed that (1) multilineage involvement was present in 53% of BCR::ABL1 and 36% of KMT2A-rearranged B-ALL regardless of age, (2) multilineage involvement created pitfalls for residual disease monitoring, and (3) HSPC transcriptome signatures were upregulated in KMT2A-rearranged B-ALL with multilineage involvement. Conclusions: In summary, multilineage involvement is common in both BCR::ABL1-rearranged and KMT2A-rearranged B-ALL, which should be taken into consideration when interpreting the disease burden during the clinical course.
Language	English
Publishing date	2024-04-30
Publishing country	England
Document type	Journal Article
ZDB-ID	131914-0
ISSN	1365-2559 ; 0309-0167
ISSN (online)	1365-2559
ISSN	0309-0167
DOI	10.1111/his.15203
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