ArticleBreast cancer research : BCR2018
Paternal malnutrition programs breast cancer risk and tumor metabolism in offspring.
Article in Breast cancer research : BCR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- Pooled it
- Metabolic immune checkpoints (MICs) in cancer: from molecular mechanisms to challenges and opportunities in clinical translation.Signal transduction and targeted therapy · 2026Review
- Environmentally-induced sperm RNAs shape placentation and fetal growth.Research square · 2026Article
- Paternal Malnutrition has Organ-Specific Intergenerational Effects on Mitochondrial Function and Oxidative Stress Induced DNA Damage in Male Mouse Offspring.Molecular nutrition & food research · 2026Article
- Probing the Influence of Paternal Diet on Offspring Neuroanatomy With Mouse MRI.Brain and behavior · 2026Article
- Nutrition-Based Paternal Influence on Gynecological Diseases in Female Offspring via Epigenetic Mechanisms.Nutrients · 2025Review
- Building climate resilience and mitigating the impact of climate change on cancer care: strategies and solutions for low and middle income countries.Cancer causes & control : CCC · 2025Review
- Association of Paternal BMI and Diet During Pregnancy with Offspring Birth Measures: The STEPS Study.Nutrients · 2025Article
- Berberine Inhibits Breast Cancer Stem Cell Development and Decreases Inflammation: Involvement of miRNAs and IL-6.Current developments in nutrition · 2025Article
- The Impact of Parental Preconception Nutrition, Body Weight, and Exercise Habits on Offspring Health Outcomes: A Narrative Review.Nutrients · 2024Review
- Paternal undernutrition and overnutrition modify semen composition and preimplantation embryo developmental kinetics in mice.BMC biology · 2024Article
- Preconceptional paternal caloric restriction of high-fat diet-induced obesity in Wistar rats dysregulates the metabolism of their offspring via AMPK/SIRT1 pathway.Lipids in health and disease · 2024Article
- Paternal dietary macronutrient balance and energy intake drive metabolic and behavioral differences among offspring.Nature communications · 2024Article
- A Free Amino Acid Diet Alleviates Colorectal Tumorigenesis through Modulating Gut Microbiota and Metabolites.Nutrients · 2024Article
- Paternal DDT exposure induces sex-specific programming of fetal growth, placenta development and offspring's health phenotypes in a mouse model.Scientific reports · 2024Article
- Review
- Investigating the Relationship between Birthweight and Breast Cancer from A Non-Linear and Mediation Perspective.Iranian journal of public health · 2024Article
- The impact of sarcopenia on nutritional status in elderly patients with gastrointestinal tumors.Scientific reports · 2023Article
- The hunger strikes back: an epigenetic memory for autophagy.Cell death and differentiation · 2023Review
- Developmental origins of health and disease: Impact of paternal nutrition and lifestyle.Pediatric investigation · 2023Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundWhile many studies have shown that maternal factors in pregnancy affect the cancer risk for offspring, few studies have investigated the impact of paternal exposures on their progeny's risk of this disease. Population studies generally show a U-shaped association between birthweight and breast cancer risk, with both high and low birthweight increasing the risk compared with average birthweight. Here, we investigated whether paternal malnutrition would modulate the birthweight and later breast cancer risk of daughters.
methodsMale mice were fed AIN93G-based diets containing either 17.7% (control) or 8.9% (low-protein (LP)) energy from protein from 3 to 10 weeks of age. Males on either group were mated to females raised on a control diet. Female offspring from control and LP fathers were treated with 7,12-dimethylbenz[a]anthracene (DMBA) to initiate mammary carcinogenesis. Mature sperm from fathers and mammary tissue and tumors from female offspring were used for epigenetic and other molecular analyses.
resultsWe found that paternal malnutrition reduces the birthweight of daughters and leads to epigenetic and metabolic reprogramming of their mammary tissue and tumors. Daughters of LP fathers have higher rates of mammary cancer, with tumors arising earlier and growing faster than in controls. The energy sensor, the AMP-activated protein kinase (AMPK) pathway, is suppressed in both mammary glands and tumors of LP daughters, with consequent activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, LP mammary tumors show altered amino-acid metabolism with increased glutamine utilization. These changes are linked to alterations in noncoding RNAs regulating those pathways in mammary glands and tumors. Importantly, we detect alterations in some of the same microRNAs/target genes found in our animal model in breast tumors of women from populations where low birthweight is prevalent.
conclusionsOur study suggests that ancestral paternal malnutrition plays a role in programming offspring cancer risk and phenotype by likely providing a metabolic advantage to cancer cells.
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Registered trials
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.