Evidence map›Paper›PMID 42639030›Full record

ArticleEnvironmental epigenetics2026

Weighted epigenetic site correlation network analysis of chemotherapy impacts on osteosarcoma cancer survivors' male fertility, sperm, and endocrine parameters.

Margarett Shnorhavorian, John K Amory, Stephen M Schwartz, Smita Bhatia, Saro Armenian, Holcombe E Grier, Eric J Chow, Rashmi Joshi, Daniel Beck, Michael K Skinner

Abstract read
In one paragraph

Article in Environmental epigenetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Margarett ShnorhavorianSeattle Children's Hospital, Seattle, WA 98105, United States.
John K AmoryUniversity of Washington, Center for Research in Reproduction and Contraception, Seattle, WA 98195, United States.
Stephen M SchwartzFred Hutchinson Cancer Center, Seattle, WA 98109, United States.
Smita BhatiaInstitute for Cancer Outcomes and Survivorship, University Alabama at Birmingham, Birmingham, AL 35233, United States.ORCID https://orcid.org/0000-0002-7755-5683
Saro ArmenianCity Hope Hospital, Comprehensive Cancer Center, Department of Pediatrics, Duarte, CA 91010, United States.ORCID https://orcid.org/0000-0003-2604-8603
Holcombe E GrierDana-Farber, Boston Children's Center, Boston, MA 02115, United States.
Eric J ChowFred Hutchinson Cancer Center, Seattle, WA 98109, United States.
Rashmi JoshiCenter for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, WA 99164, United States.
Daniel BeckCenter for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, WA 99164, United States.
Michael K SkinnerCenter for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, WA 99164, United States.ORCID https://orcid.org/0000-0001-8224-2078

Funding

NCTN BIQSFP ANBL1531 (NRT)U10CA180886 · NCI · PUBLIC HEALTH INSTITUTE · PI Douglas S. Hawkins · 2014 to 2026
$390.6M
COG FOREIGN ACCRUALU10CA098543 · NCI · NATIONAL CHILDHOOD CANCER FOUNDATION · PI ADAMSON, PETER C. · 2003 to 2013
$335.5M
Towards a preventive cancer vaccine for children with constitutional mismatch repair deficiencyUG1CA189955 · NCI · PUBLIC HEALTH INSTITUTE · PI BRAD H POLLOCK, Michael E. Roth · 2014 to 2026
$62.5M
Testicular effects of modern chemotherapy regimens in osteosarcoma survivorsR01CA175216 · NCI · SEATTLE CHILDREN'S HOSPITAL · PI SHNORHAVORIAN, MARGARETT · 2016 to 2022
$3.2M
NCI NIH HHS R01 CA175216NCI NIH HHS U10 CA098543NCI NIH HHS U10 CA180886NCI NIH HHS UG1 CA189955
6 · The paper itself

Abstract

The impacts of chemotherapy exposure on adolescent male osteosarcoma survivors as adults were investigated using a number of physiological parameters, with a focus on chemotherapy, reproduction, and sperm. The Children's Oncology Group (COG) clinical sites (protocol ALTE16C1) of previously collected and stored sperm samples were obtained for this analysis. The epigenetic DNA methylation alterations in sperm were assessed in 176 control adult male patients' sperm, and 183 chemotherapy-exposed osteosarcoma survivors' adult male sperm were provided by COG sites. The current study used a weighted gene co-expression network analysis computational approach that was adopted for use as a weighted epigenetic site correlation network analysis. This analysis identified correlation coefficients between differential DNA methylation regions and other DNA methylation sites with physiological and chemotherapy parameters. Module-trait relationships in the data were determined for epigenetic modules, which highly correlated with sperm parameters, reproductive hormones, and several chemotherapies (e.g. cisplatin). Gene associations of these epigenetic sites were identified and correlated to chemotherapy-associated genes and pathways, as well as reproductive parameters. Observations demonstrate dramatic impacts of adolescent chemotherapy on later adult life sperm epigenetics. Clearly, epigenetics has the potential to mediate the actions of chemotherapy on later life physiology and may potentially impact future generations through epigenetic transgenerational inheritance mechanisms, but this needs further investigation.

Indexed as

chemotherapyDNA methylationendocrineepigeneticsgene associationsmale infertilityosteosarcomaspermWGCNAwhole epigenome-wide correlation network analysis

Identifiers

PMID42639030
PMCPMC13501531

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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.