SynthesisCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology2022
Association Study between Polymorphisms in DNA Methylation-Related Genes and Testicular Germ Cell Tumor Risk.
Synthesis in Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
0.8field-weighted citation impact, top 31% of its field
1 · What the graph read from it
What it found
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2 · The registry
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3 · Its place in the literature
Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.
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5 · Who and what money
Authors and funding
47 authors at 20 institutions in 13 countries.
Chiara GrassoCancer Epidemiology Unit, Department of Medical Sciences, University of Turin and CPO Piedmont, Turin, Italy.ORCID 0000-0002-2597-4990
Maja PopovicCancer Epidemiology Unit, Department of Medical Sciences, University of Turin and CPO Piedmont, Turin, Italy.ORCID 0000-0003-4500-6572
Elena IsaevskaCancer Epidemiology Unit, Department of Medical Sciences, University of Turin and CPO Piedmont, Turin, Italy.ORCID 0000-0002-1846-7990
Fulvio LazzaratoCancer Epidemiology Unit, Department of Medical Sciences, University of Turin and CPO Piedmont, Turin, Italy.ORCID 0000-0002-6698-5944
Valentina FianoCancer Epidemiology Unit, Department of Medical Sciences, University of Turin and CPO Piedmont, Turin, Italy.ORCID 0000-0001-7978-372X
Daniela ZugnaCancer Epidemiology Unit, Department of Medical Sciences, University of Turin and CPO Piedmont, Turin, Italy.ORCID 0000-0002-5122-6144
John PlutaDivision of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.ORCID 0000-0002-8941-6242
Benita WeathersDivision of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.ORCID 0000-0002-5675-8334
Kurt D'AndreaDivision of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.ORCID 0000-0001-7005-3800
Kristian AlmstrupDepartment of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.ORCID 0000-0002-1832-0307
Lynn Anson-CartwrightDepartment of Surgery (Urology), University of Toronto and The Princess Margaret Cancer Centre, Toronto, Ontario, Canada.ORCID 0000-0002-7726-9695
D Timothy BishopDepartment of Haematology and Immunology, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, United Kingdom.ORCID 0000-0002-8752-8785
Stephen J ChanockDivision of Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.ORCID 0000-0002-2324-3393
Chu ChenProgram in Epidemiology, Fred Hutchinson Cancer Center, Seattle, Washington.ORCID 0000-0003-2267-8050
Victoria K CortessisDepartment of Population and Public Health Sciences, and Obstetrics and Gynecology, Keck School of Medicine at the University of Southern California, Los Angeles, California.ORCID 0000-0002-2339-1089
Marlene D DalgaardDepartment of Health Technology, Technical University of Denmark, Lyngby, Denmark.ORCID 0000-0002-4036-6408
Siamak DaneshmandDepartment of Urology, Keck School of Medicine at the University of Southern California, Los Angeles, California.ORCID 0000-0001-6224-9598
Alberto FerlinUnit of Andrology and Reproductive Medicine, Department of Medicine, University of Padova, Padova, Italy.ORCID 0000-0001-5817-8141
Carlo ForestaUnit of Andrology and Reproductive Medicine, Department of Medicine, University of Padova, Padova, Italy.ORCID 0000-0002-6576-2183
Megan N FroneDivision of Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.ORCID 0000-0001-8273-8866
Marija GamulinDepartment of Oncology, University Hospital Centre Zagreb, University of Zagreb School of Medicine, Zagreb, Croatia.ORCID 0000-0003-2431-7910
Jourik A GietemaDepartment of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.ORCID 0000-0003-0629-7354
Mark H GreeneDivision of Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.ORCID 0000-0003-1852-9239
Tom GrotmolDepartment of Research, Cancer Registry of Norway, Oslo, Norway.ORCID 0000-0001-5698-4350
Robert J HamiltonDepartment of Surgery (Urology), University of Toronto and The Princess Margaret Cancer Centre, Toronto, Ontario, Canada.ORCID 0000-0002-6715-5934
Trine B HaugenFaculty of Health Sciences, OsloMet - Oslo Metropolitan University, Oslo, Norway.ORCID 0000-0002-8814-3393
Russ HauserDepartment of Environmental Health, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts.ORCID 0000-0002-1899-3982
Robert KarlssonDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-8949-2587
Lambertus A KiemeneyRadboud University Medical Center, Nijmegen, the Netherlands.ORCID 0000-0002-2368-1326
Davor LesselInstitute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.ORCID 0000-0003-4496-244X
Patrizia ListaDivision of Medical Oncology, AOU "Città della Salute e della Scienza di Torino", Turin, Italy.ORCID 0000-0002-9643-908X
Ragnhild A LotheDepartment of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway.ORCID 0000-0002-1693-1032
Chey LovedayDivision of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom.ORCID 0000-0002-2291-372X
Coby MeijerDepartment of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.ORCID 0000-0001-5283-8516
Kevin T NeadDepartment of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0001-9680-8298
Jérémie NsengimanaBiostatistics Research Group, Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle, United Kingdom.ORCID 0000-0002-3603-4208
Rolf I SkotheimDepartment of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway.ORCID 0000-0002-5609-4048
Clare TurnbullDivision of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom.ORCID 0000-0002-1734-5772
David J VaughnDivision of Hematology and Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.ORCID 0000-0002-7319-7719
Fredrik WiklundDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-4623-0544
Tongzhang ZhengDepartment of Epidemiology, Brown School of Public Health, Brown University, Providence, Rhode Island.ORCID 0000-0003-0155-7540
Andrea ZitellaDivision of Urology, Department of Surgical Science, AOU "Città della Salute e della Scienza di Torino", University of Turin, Turin, Italy.ORCID 0000-0001-7331-2521
Stephen M SchwartzProgram in Epidemiology, Fred Hutchinson Cancer Center, Seattle, Washington.ORCID 0000-0001-7499-8502
Katherine A McGlynnDivision of Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.ORCID 0000-0003-2329-9933
Peter A KanetskyDepartment of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.ORCID 0000-0002-5567-9618
Katherine L NathansonDivision of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.ORCID 0000-0002-6740-0901
Lorenzo RichiardiCancer Epidemiology Unit, Department of Medical Sciences, University of Turin and CPO Piedmont, Turin, Italy.ORCID 0000-0003-0316-9402
Department of Medical Sciences · BYNational Cancer Institute · USTranslational Therapeutics (United States) · USAzienda Ospedaliera Citta' della Salute e della Scienza di Torino · ITCape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa · ZAKarolinska Institutet · SEOslo University Hospital · NOPrincess Margaret Cancer Centre · CAUniversity Medical Center Groningen · NLUniversity of Padua · ITUniversity of Southern California · USBrown University · USCancer Registry of Norway · NOCancer Research UK · GBHarvard University · USMoffitt Cancer Center · USNewcastle University · GBOsloMet – Oslo Metropolitan University · NORadboud University Nijmegen · NLRoyal Marsden NHS Foundation Trust · GB
Funding
UNIVERSITY OF PENNSYLVANIA CAN CTR SUPPORT GRANTP30CA016520 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Robert H. Vonderheide · 1985 to 2026
$222.3M
Hormone-Related CancersZIACP010126 · NCI · DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS · PI GIERACH, GRETCHEN · 2009 to 2025
$103.5M
Post GWA Studies in Testicular Germ Cell TumorsU01CA164947 · NCI · UNIVERSITY OF PENNSYLVANIA · PI KANETSKY, PETER A, NATHANSON, KATHERINE L. · 2012 to 2024
$11.7M
MOLECULAR EPIDEMIOLOGY OF TESTICULAR CARCINOMAR01CA085914 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI SCHWARTZ, STEPHEN M · 2000 to 2009
$8.4M
Environment, Gene and Testicular Cancer RiskR01CA104786 · NCI · YALE UNIVERSITY · PI ZHENG, TONGZHANG · 2006 to 2010
$4.9M
A Genetic Linkage Study of Testicular CancerR01CA102042 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CORTESSIS, VICTORIA K · 2004 to 2009
$3.9M
Inherited genetic variation and predisposition to testicular germ cell tumorR01CA114478 · NCI · UNIVERSITY OF PENNSYLVANIA · PI NATHANSON, KATHERINE L. · 2007 to 2011
$3.1M
Impact of clonal hematopoiesis mutations on toxicity and outcomes following oncologic therapyK08CA263313 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI NEAD, KEVIN THOMAS · 2021 to 2025
$1.2M
Clinical/Genetic Studies of Family/Hereditary CancersZ01CP010144 · NCI · DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS · PI GREENE, MARK H · 2000 to 2008
$1.1M
SURVEILLANCE EPIDEMIOLOGY &END RESULTS PROGRAMN01CN067009 · CN · FRED HUTCHINSON CANCER RESEARCH CENTER · PI THOMAS, DAVID B · 1996 to 1997
backgroundTesticular germ cell tumors (TGCT), histologically classified as seminomas and nonseminomas, are believed to arise from primordial gonocytes, with the maturation process blocked when they are subjected to DNA methylation reprogramming. SNPs in DNA methylation machinery and folate-dependent one-carbon metabolism genes have been postulated to influence the proper establishment of DNA methylation.
methodsIn this pathway-focused investigation, we evaluated the association between 273 selected tag SNPs from 28 DNA methylation-related genes and TGCT risk. We carried out association analysis at individual SNP and gene-based level using summary statistics from the Genome Wide Association Study meta-analysis recently conducted by the international Testicular Cancer Consortium on 10,156 TGCT cases and 179,683 controls.
resultsIn individual SNP analyses, seven SNPs, four mapping within MTHFR, were associated with TGCT risk after correction for multiple testing (q ≤ 0.05). Queries of public databases showed that three of these SNPs were associated with MTHFR changes in enzymatic activity (rs1801133) or expression level in testis tissue (rs12121543, rs1476413). Gene-based analyses revealed MTHFR (q = 8.4 × 10-4), methyl-CpG-binding protein 2 (MECP2; q = 2 × 10-3), and ZBTB4 (q = 0.03) as the top TGCT-associated genes. Stratifying by tumor histology, four MTHFR SNPs were associated with seminoma. In gene-based analysis MTHFR was associated with risk of seminoma (q = 2.8 × 10-4), but not with nonseminomatous tumors (q = 0.22).
conclusionsGenetic variants within MTHFR, potentially having an impact on the DNA methylation pattern, are associated with TGCT risk. IMPACT: This finding suggests that TGCT pathogenesis could be associated with the folate cycle status, and this relation could be partly due to hereditary factors.
Indexed as
Neoplasms, Germ Cell and EmbryonalSeminomaTesticular NeoplasmsDNA MethylationFolic AcidGenome-Wide Association StudyHumansMalePolymorphism, Single NucleotideFolic Acid
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.
Association Study between Polymorphisms in DNA Methylation-Related Genes and Testicular Germ Cell Tumor Risk. · full record | OpenQuestion