bims-medica Biomed News
on Metabolism and diet in cancer
Issue of 2025–01–19
thirteen papers selected by
Brett Chrest, Wake Forest University
  1. Plasma metabolomic signature of a proinflammatory diet in relation to breast cancer risk: a prospective cohort study.
  2. Dietary-Lifestyle Patterns and Colorectal Cancer Risk: Global Cancer Update Programme (CUP Global) Systematic Literature Review.
  3. Lactylation fuels nucleotide biosynthesis and facilitates deuterium metabolic imaging of tumor proliferation in H3K27M-mutant gliomas.
  4. Metabolic Signaling in the Tumor Microenvironment.
  5. Primary Roles of Branched Chain Amino Acids (BCAAs) and Their Metabolism in Physiology and Metabolic Disorders.
  6. Disease stage-specific role of the mitochondrial pyruvate carrier suppresses differentiation in temozolomide and radiation-treated glioblastoma.
  7. Multiplex genome editing eliminates lactate production without impacting growth rate in mammalian cells.
  8. In vivo itaconate tracing reveals degradation pathway and turnover kinetics.
  9. Glutaminase-2 Expression Induces Metabolic Changes and Regulates Pyruvate Dehydrogenase Activity in Glioblastoma Cells.
  10. Ketogenic diet and cancer: multidimensional exploration and research.
  11. Co-targeting of metabolism using dietary and pharmacologic approaches reduces breast cancer metastatic burden.
  12. Bioenergetic adaptations of small intestinal epithelial cells reduce cell differentiation enhancing intestinal permeability in obese mice.
  13. Association of whole grain food consumption with lung cancer risk: a prospective cohort study.
  1. Am J Clin Nutr. 2025 Jan 11. pii: S0002-9165(25)00013-9. [Epub ahead of print]
    Plasma metabolomic signature of a proinflammatory diet in relation to breast cancer risk: a prospective cohort study.
    Miao Long, Xikang Fan, Mian Wang, Xinyi Liu, Chengqu Fu, Jianv Huang, Yuefan Shen, Xueni Cheng, Pengfei Luo, Jian Su, Jinyi Zhou, Dong Hang.
       BACKGROUND: A proinflammatory diet has been linked to an increased risk of breast cancer. However, the underlying metabolic roles remain to be elucidated.
    OBJECTIVE: To investigate the metabolic mechanism between proinflammatory diet and breast cancer risk.
    METHODS: This prospective study included 273,324 females from the UK Biobank. The dietary inflammatory potential was assessed via an energy-adjusted dietary inflammatory index (E-DII) based on a 24-hour recall questionnaire. The plasma metabolome was profiled via high-throughput nuclear magnetic resonance spectroscopy (NMR). A metabolic signature was constructed by summing selected metabolite concentrations weighted by the coefficients via absolute shrinkage and selection operator (LASSO) analysis. Multivariate Cox regression was applied to assess the associations of the E-DII and metabolic signature with breast cancer risk.
    RESULTS: We constructed a metabolic signature comprising 26 metabolites associated with a proinflammatory diet. These metabolites primarily included lipoproteins, amino acids, fatty acids, and ketone bodies. Both the E-DII and metabolic signature were positively associated with breast cancer risk (hazard ratio [HR] comparing the highest quintile to the lowest quintile = 1.17, 95% confidence interval [CI] = (1.04, 1.32); and 1.21, 95% CI = (1.01, 1.46), respectively). Furthermore, we found that saturated fatty acids to total fatty acids percentage and acetone concentration were positively associated (HR = 1.20, 95% CI = (1.04, 1.37); 1.15, 95% CI = (1.01, 1.32), respectively), while the degree of unsaturation was inversely associated with breast cancer risk (HR = 0.86; 95% CI = 0.75, 0.99).
    CONCLUSION: We identified a metabolic signature that reflects a proinflammatory diet and is associated with an increased risk of breast cancer.
    Keywords:  Breast cancer; Dietary inflammatory index; Metabolic signature; Metabolomics; Proinflammatory diet
    DOI:  https://doi.org/10.1016/j.ajcnut.2025.01.013
  2. Am J Clin Nutr. 2025 Jan 11. pii: S0002-9165(25)00014-0. [Epub ahead of print]
    Dietary-Lifestyle Patterns and Colorectal Cancer Risk: Global Cancer Update Programme (CUP Global) Systematic Literature Review.
    Anne H Y Chu, Kehuan Lin, Helen Croker, Sarah Kefyalew, Georgios Markozannes, Konstantinos K Tsilidis, Yikyung Park, John Krebs, Matty P Weijenberg, Monica L Baskin, Ellen Copson, Sarah J Lewis, Jacob C Seidell, Rajiv Chowdhury, Lynette Hill, Doris S M Chan, Dong Hoon Lee, Edward L Giovannucci.
       BACKGROUND: While healthy dietary and lifestyle factors have been individually linked to lower colorectal cancer (CRC) risks, recommendations for whole diet-lifestyle patterns remained unestablished due to limited studies and inconsistent pattern definitions.
    OBJECTIVE: This updated review synthesized literature on dietary-lifestyle patterns and CRC risk/mortality.
    METHODS: PubMed and Embase were searched through 31 March 2023 for randomized controlled trials and prospective cohort studies examining adulthood dietary patterns combined with modifiable lifestyle factors such as adiposity, smoking, alcohol consumption, physical activity, and/or others. Patterns were categorized by derivation methods: a priori, a posteriori, and a hybrid combining both; and were then descriptively reviewed for the primary outcomes: CRC risk or mortality. The Global Cancer Update Programme Expert Committee and Expert Panel independently graded the evidence on the likelihood of causality using pre-defined grading criteria.
    RESULTS: Thirty-three observational studies were reviewed. 'Strong-probable' evidence was concluded for higher levels of alignment with the a priori-derived World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) recommendations score and lower CRC risk; and 'limited-suggestive' evidence for the American Cancer Society guidelines and Healthy Lifestyle Index with lower CRC risk (mainly due to concerns about risk of bias for confounding). A posteriori-derived patterns lack firm evidence (only one study). 'Strong-probable' evidence was concluded for higher levels of alignment with the Empirical Lifestyle Index for Hyperinsulinemia hybrid pattern and higher CRC risk. By cancer subsite, only the WCRF/AICR recommendations score showed 'strong-probable' evidence with lower colon cancer risk. All exposure-mortality pairs were graded 'limited-no conclusion'. The evidence for other pattern-outcome associations was graded as 'limited-no conclusion'.
    CONCLUSIONS: Adopting a healthy pattern of diet, maintaining a healthy weight, staying physically active, and embracing health-conscious habits, such as avoiding tobacco and moderating alcohol, are collectively associated with a lower CRC risk. Healthy lifestyle habits are key to primary CRC prevention.
    Keywords:  Adult; Colorectal Cancers; Dietary Patterns; Epidemiology; Incidences; Lifestyle; Mortalities; Prospective Studies; Public Health; Review
    DOI:  https://doi.org/10.1016/j.ajcnut.2025.01.014
  3. bioRxiv. 2025 Jan 03. pii: 2025.01.02.631150. [Epub ahead of print]
    Lactylation fuels nucleotide biosynthesis and facilitates deuterium metabolic imaging of tumor proliferation in H3K27M-mutant gliomas.
    Georgios Batsios, Céline Taglang, Suresh Udutha, Anne Marie Gillespie, Simon P Robinson, Timothy Phoenix, Sabine Mueller, Sriram Venneti, Carl Koschmann, Pavithra Viswanath.
      Oncogenes hyperactive lactate production, but the mechanisms by which lactate facilitates tumor growth are unclear. Here, we demonstrate that lactate is essential for nucleotide biosynthesis in pediatric diffuse midline gliomas (DMGs). The oncogenic histone H3K27M mutation upregulates phosphoglycerate kinase 1 (PGK1) and drives lactate production from [U- 13 C]-glucose in DMGs. Lactate activates the nucleoside diphosphate kinase NME1 via lactylation and promotes the synthesis of nucleoside triphosphates essential for tumor proliferation. Importantly, we show that this mechanistic link between glycolysis and nucleotide biosynthesis provides a unique opportunity for deuterium metabolic imaging of DMGs. Spatially mapping 2 H-lactate production from [6,6- 2 H]-glucose allows visualization of the metabolically active tumor lesion and provides an early readout of response to standard-of-care radiation and targeted therapy that precedes extended survival and reflects pharmacodynamic alterations at the tissue level in preclinical DMG models in vivo at clinical field strength (3T). In essence, we have identified an H3K27M-lactate-NME1 axis that promotes DMG proliferation and facilitates non-invasive metabolic imaging of DMGs.
    STATEMENT OF SIGNIFICANCE: This study establishes a role for lactate in driving nucleotide biosynthesis in DMGs. Importantly, imaging lactate production from glucose using DMI provides a readout of tumor proliferation and early response to therapy in clinically relevant DMG models. Our studies lay the foundation for precision metabolic imaging of DMG patients.
    DOI:  https://doi.org/10.1101/2025.01.02.631150
  4. Cancers (Basel). 2025 Jan 06. pii: 155. [Epub ahead of print]17(1):
    Metabolic Signaling in the Tumor Microenvironment.
    Ryan Clay, Kunyang Li, Lingtao Jin.
      Cancer cells must reprogram their metabolism to sustain rapid growth. This is accomplished in part by switching to aerobic glycolysis, uncoupling glucose from mitochondrial metabolism, and performing anaplerosis via alternative carbon sources to replenish intermediates of the tricarboxylic acid (TCA) cycle and sustain oxidative phosphorylation (OXPHOS). While this metabolic program produces adequate biosynthetic intermediates, reducing agents, ATP, and epigenetic remodeling cofactors necessary to sustain growth, it also produces large amounts of byproducts that can generate a hostile tumor microenvironment (TME) characterized by low pH, redox stress, and poor oxygenation. In recent years, the focus of cancer metabolic research has shifted from the regulation and utilization of cancer cell-intrinsic pathways to studying how the metabolic landscape of the tumor affects the anti-tumor immune response. Recent discoveries point to the role that secreted metabolites within the TME play in crosstalk between tumor cell types to promote tumorigenesis and hinder the anti-tumor immune response. In this review, we will explore how crosstalk between metabolites of cancer cells, immune cells, and stromal cells drives tumorigenesis and what effects the competition for resources and metabolic crosstalk has on immune cell function.
    Keywords:  cancer metabolism; immune response; oncometabolite; tumor microenvironment
    DOI:  https://doi.org/10.3390/cancers17010155
  5. Molecules. 2024 Dec 27. pii: 56. [Epub ahead of print]30(1):
    Primary Roles of Branched Chain Amino Acids (BCAAs) and Their Metabolism in Physiology and Metabolic Disorders.
    Tomoki Bo, Junichi Fujii.
      Leucine, isoleucine, and valine are collectively known as branched chain amino acids (BCAAs) and are often discussed in the same physiological and pathological situations. The two consecutive initial reactions of BCAA catabolism are catalyzed by the common enzymes referred to as branched chain aminotransferase (BCAT) and branched chain α-keto acid dehydrogenase (BCKDH). BCAT transfers the amino group of BCAAs to 2-ketoglutarate, which results in corresponding branched chain 2-keto acids (BCKAs) and glutamate. BCKDH performs an oxidative decarboxylation of BCKAs, which produces their coenzyme A-conjugates and NADH. BCAT2 in skeletal muscle dominantly catalyzes the transamination of BCAAs. Low BCAT activity in the liver reduces the metabolization of BCAAs, but the abundant presence of BCKDH promotes the metabolism of muscle-derived BCKAs, which leads to the production of glucose and ketone bodies. While mutations in the genes responsible for BCAA catabolism are involved in rare inherited disorders, an aberrant regulation of their enzymatic activities is associated with major metabolic disorders such as diabetes, cardiovascular disease, and cancer. Therefore, an understanding of the regulatory process of metabolic enzymes, as well as the functions of the BCAAs and their metabolites, make a significant contribution to our health.
    Keywords:  branched chain aminotransferase; branched chain α-keto acid dehydrogenase; cancer; diabetes; gluconeogenesis; ketogenesis
    DOI:  https://doi.org/10.3390/molecules30010056
  6. Neuro Oncol. 2025 Jan 11. pii: noaf008. [Epub ahead of print]
    Disease stage-specific role of the mitochondrial pyruvate carrier suppresses differentiation in temozolomide and radiation-treated glioblastoma.
    Emma Martell, Helgi Kuzmychova, Harshal Senthil, Ujala Chawla, Esha Kaul, Akaljot Grewal, Versha Banerji, Christopher M Anderson, Chitra Venugopal, Donald Miller, Tamra E Werbowetski-Ogilvie, Sheila K Singh, Tanveer Sharif.
       BACKGROUND: The mitochondrial pyruvate carrier (MPC), a central metabolic conduit linking glycolysis and mitochondrial metabolism, is instrumental in energy production. However, the role of the MPC in cancer is controversial. In particular, the importance of the MPC in glioblastoma (GBM) disease progression following standard temozolomide (TMZ) and radiation therapy (RT) remains unexplored.
    METHODS: Leveraging in vitro and in vivo patient-derived models of TMZ-RT treatment in GBM, we characterize the temporal dynamics of MPC abundance and downstream metabolic consequences using state-of-the-art molecular, metabolic, and functional assays.
    RESULTS: Our findings unveil a disease stage-specific role for the MPC, where in post-treatment GBM, but not therapy-naïve tumors, the MPC acts as a central metabolic regulator that suppresses differentiation. Temporal profiling reveals a dynamic metabolic rewiring where a steady increase in MPC abundance favors a shift towards enhanced mitochondrial metabolic activity across patient GBM samples. Intriguingly, while overall mitochondrial metabolism is increased, acetyl-CoA production is reduced in post-treatment GBM cells, hindering histone acetylation and silencing neural differentiation genes in an MPC-dependent manner. Finally, the therapeutic translations of these findings are highlighted by the successful pre-clinical patient-derived orthotopic xenograft (PDOX) trials utilizing a blood-brain-barrier (BBB) permeable MPC inhibitor, MSDC-0160, which augments standard TMZ-RT therapy to mitigate disease relapse and prolong animal survival.
    CONCLUSION: Our findings demonstrate the critical role of the MPC in mediating GBM aggressiveness and molecular evolution following standard TMZ-RT treatment, illuminating a therapeutically-relevant metabolic vulnerability to potentially improve survival outcomes for GBM patients.
    Keywords:  Glioblastoma; differentiation; metabolism; mitochondrial pyruvate carrier; tumor recurrence
    DOI:  https://doi.org/10.1093/neuonc/noaf008
  7. Nat Metab. 2025 Jan 14.
    Multiplex genome editing eliminates lactate production without impacting growth rate in mammalian cells.
    Hooman Hefzi, Iván Martínez-Monge, Igor Marin de Mas, Nicholas Luke Cowie, Alejandro Gomez Toledo, Soo Min Noh, Karen Julie la Cour Karottki, Marianne Decker, Johnny Arnsdorf, Jose Manuel Camacho-Zaragoza, Stefan Kol, Sanne Schoffelen, Nuša Pristovšek, Anders Holmgaard Hansen, Antonio A Miguez, Sara Petersen Bjørn, Karen Kathrine Brøndum, Elham Maria Javidi, Kristian Lund Jensen, Laura Stangl, Emanuel Kreidl, Thomas Beuchert Kallehauge, Daniel Ley, Patrice Ménard, Helle Munck Petersen, Zulfiya Sukhova, Anton Bauer, Emilio Casanova, Niall Barron, Johan Malmström, Lars K Nielsen, Gyun Min Lee, Helene Faustrup Kildegaard, Bjørn G Voldborg, Nathan E Lewis.
      The Warburg effect, which describes the fermentation of glucose to lactate even in the presence of oxygen, is ubiquitous in proliferative mammalian cells, including cancer cells, but poses challenges for biopharmaceutical production as lactate accumulation inhibits cell growth and protein production. Previous efforts to eliminate lactate production in cells for bioprocessing have failed as lactate dehydrogenase is essential for cell growth. Here, we effectively eliminate lactate production in Chinese hamster ovary and in the human embryonic kidney cell line HEK293 by simultaneous knockout of lactate dehydrogenases and pyruvate dehydrogenase kinases, thereby removing a negative feedback loop that typically inhibits pyruvate conversion to acetyl-CoA. These cells, which we refer to as Warburg-null cells, maintain wild-type growth rates while producing negligible lactate, show a compensatory increase in oxygen consumption, near total reliance on oxidative metabolism, and higher cell densities in fed-batch cell culture. Warburg-null cells remain amenable for production of diverse biotherapeutic proteins, reaching industrially relevant titres and maintaining product glycosylation. The ability to eliminate lactate production may be useful for biotherapeutic production and provides a tool for investigating a common metabolic phenomenon.
    DOI:  https://doi.org/10.1038/s42255-024-01193-7
  8. bioRxiv. 2025 Jan 02. pii: 2025.01.02.629617. [Epub ahead of print]
    In vivo itaconate tracing reveals degradation pathway and turnover kinetics.
    Hanna F Willenbockel, Alexander T Williams, Alfredo Lucas, Birte Dowerg, Pedro Cabrales, Christian M Metallo, Thekla Cordes.
      Itaconate is an immunomodulatory metabolite that alters mitochondrial metabolism and immune cell function. This organic acid is endogenously synthesized via tricarboxylic acid (TCA) metabolism downstream of TLR signaling. Itaconate-based treatment strategies are being explored to mitigate numerous inflammatory conditions. However, little is known about the turnover rate of itaconate in circulation, the kinetics of its degradation, and the broader consequences on metabolism. By combining mass spectrometry and in vivo 13 C itaconate tracing, we demonstrate that itaconate is rapidly eliminated from plasma, excreted via urine, and fuels TCA cycle metabolism specifically in the liver and kidneys. These studies further revealed that itaconate is converted into acetyl-CoA, mesaconate, and citramalate in mitochondria. Itaconate administration also influenced branched-chain amino acid metabolism and succinate levels, indicating a functional impact on succinate dehydrogenase (SDH) and methylmalonyl-CoA mutase (MUT) activity. Our findings uncovered a previously unknown aspect of the itaconate metabolism, highlighting its rapid catabolism in vivo that contrasts findings in cultured cells.
    DOI:  https://doi.org/10.1101/2025.01.02.629617
  9. Int J Mol Sci. 2025 Jan 06. pii: 427. [Epub ahead of print]26(1):
    Glutaminase-2 Expression Induces Metabolic Changes and Regulates Pyruvate Dehydrogenase Activity in Glioblastoma Cells.
    Juan De Los Santos-Jiménez, José A Campos-Sandoval, Tracy Rosales, Bookyung Ko, Francisco J Alonso, Javier Márquez, Ralph J DeBerardinis, José M Matés.
      Glutaminase controls the first step in glutaminolysis, impacting bioenergetics, biosynthesis and oxidative stress. Two isoenzymes exist in humans, GLS and GLS2. GLS is considered prooncogenic and overexpressed in many tumours, while GLS2 may act as prooncogenic or as a tumour suppressor. Glioblastoma cells usually lack GLS2 while they express high GLS. We investigated how GLS2 expression modifies the metabolism of glioblastoma cells, looking for changes that may explain GLS2's potential tumour suppressive role. We developed LN-229 glioblastoma cells stably expressing GLS2 and performed isotope tracing using U-13C-glutamine and metabolomic quantification to analyze metabolic changes. Treatment with GLS inhibitor CB-839 was also included to concomitantly inhibit endogenous GLS. GLS2 overexpression resulted in extensive metabolic changes, altering the TCA cycle by upregulating part of the cycle but blocking the synthesis of the 6-carbon intermediates from acetyl-CoA. Expression of GLS2 caused downregulation of PDH activity through phosphorylation of S293 of PDHA1. GLS2 also altered nucleotide levels and induced the accumulation of methylated metabolites and S-adenosyl methionine. These changes suggest that GLS2 may be a key regulator linking glutamine and glucose metabolism, also impacting nucleotides and epigenetics. Future research should ascertain the mechanisms involved and the generalizability of these findings in cancer or physiological conditions.
    Keywords:  cancer; glioblastoma; glutaminase; glutaminase-2; glutamine; metabolomics; pyruvate dehydrogenase
    DOI:  https://doi.org/10.3390/ijms26010427
  10. Sci China Life Sci. 2025 Jan 14.
    Ketogenic diet and cancer: multidimensional exploration and research.
    Shiyun Wan, Xiaoxue Zhou, Feng Xie, Fangfang Zhou, Long Zhang.
      The ketogenic diet (KD) has attracted attention in recent years for its potential anticancer effects. KD is a dietary structure of high fat, moderate protein, and extremely low carbohydrate content. Originally introduced as a treatment for epilepsy, KD has been widely applied in weight loss programs and the management of metabolic diseases. Previous studies have shown that KD can potentially inhibit the growth and spread of cancer by limiting energy supply to tumor cells, thereby inhibiting tumor angiogenesis, reducing oxidative stress in normal cells, and affecting cancer cell signaling and other processes. Moreover, KD has been shown to influence T-cell-mediated immune responses and inflammation by modulating the gut microbiota, enhance the efficacy of standard cancer treatments, and mitigate the complications of chemotherapy. However, controversies and uncertainties remain regarding the specific mechanisms and clinical effects of KD as an adjunctive therapy for cancer. Therefore, this review summarizes the existing research and explores the intricate relationships between KD and cancer treatment.
    Keywords:  cancer; immune response; ketogenic diet; metabolism; therapy
    DOI:  https://doi.org/10.1007/s11427-023-2637-2
  11. NPJ Breast Cancer. 2025 Jan 14. 11(1): 3
    Co-targeting of metabolism using dietary and pharmacologic approaches reduces breast cancer metastatic burden.
    Qianying Zuo, Jin Young Yoo, Erik R Nelson, Matthew J Sikora, Rebecca B Riggins, Zeynep Madak-Erdogan.
      Patients with metastatic breast cancer face reduced quality of life and increased mortality rates, necessitating more effective anti-cancer strategies. Building on previous research that identified metastatic-niche-specific metabolic vulnerabilities, we investigated how a ketogenic diet enhances estrogen receptor (ER)-positive liver metastatic breast cancer's response to Fulvestrant (Fulv) treatment. Using in vitro cell lines and in vivo xenograft metastasis mouse models, we examined the molecular mechanisms of combining ER targeting with a ketogenic diet. We found that Fulv treatment downregulates the ketogenesis pathway enzyme OXCT1, leading to β-hydroxybutyrate accumulation and decreased tumor cell viability. We also explored interactions between glucose, palmitic acid, and β-hydroxybutyric acid. These findings establish the molecular basis and clinical potential of a ketogenic diet to enhance Fulv efficacy in patients with ER+ liver metastatic breast cancer, potentially improving survival outcomes and quality of life in this population.
    DOI:  https://doi.org/10.1038/s41523-024-00715-6
  12. Mol Metab. 2025 Jan 13. pii: S2212-8778(25)00005-5. [Epub ahead of print] 102098
    Bioenergetic adaptations of small intestinal epithelial cells reduce cell differentiation enhancing intestinal permeability in obese mice.
    Thomas Guerbette, Vincent Ciesielski, Manon Brien, Daniel Catheline, Roselyne Viel, Mégane Bostoen, Jean-Baptiste Perrin, Agnès Burel, Régis Janvier, Vincent Rioux, Annaïg Lan, Gaëlle Boudry.
       BACKGROUND: Obesity and overweight are associated with low-grade inflammation induced by adipose tissue expansion and perpetuated by altered intestinal homeostasis, including increased epithelial permeability. Intestinal epithelium functions are supported by intestinal epithelial cells (IEC) mitochondria function.
    METHODS AND RESULTS: Here, we report that diet-induced obesity (DIO) in mice induces lipid metabolism adaptations favoring lipid storage in IEC together with reduced number, altered dynamics and diminished oxidative phosphorylation activity of IEC mitochondria. Using the jejunal epithelial cell line IPEC-J2, we showed that IEC lipid metabolism and oxidative stress machinery adaptations preceded mitochondrial bioenergetic ones. Moreover, we unraveled the intricate link between IEC energetic status and proliferation / differentiation balance since enhancing mitochondrial function with the AMPK activator AICAR in jejunal organoids reduced proliferation and initiated IEC differentiation and conversely. We confirmed that the reduced IEC mitochondrial function observed in DIO mice was associated with increased proliferation and reduced differentiation, promoting expression of the permissive Cldn2 in the jejunal epithelium of DIO mice.
    CONCLUSIONS: Our study provides new insights into metabolic adaptations of IEC in obesity by revealing that excess lipid intake diminishes mitochondrial number in IEC, reducing IEC differentiation that contribute to increased epithelial permeability.
    Keywords:  high fat diet; intestine; lipid metabolism; mitochondria; obesity
    DOI:  https://doi.org/10.1016/j.molmet.2025.102098
  13. Cancer Cell Int. 2025 Jan 14. 25(1): 14
    Association of whole grain food consumption with lung cancer risk: a prospective cohort study.
    Kanran Wang, Junhan Zhao, Dingyi Yang, Mao Sun, Yongzhong Wu, Wei Zhou.
       BACKGROUND: Whether the intake of whole grain foods can protect against lung cancer is a long-standing question of considerable public health import, but the epidemiologic evidence has been limited. Therefore we aim to investigate the relationship between whole grain food consumption and lung cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) cohort.
    METHODS: Diet was assessed with a self-administered Diet History Questionnaire (DHQ) at baseline. All incident lung cancer cases were pathologically verified. Hazard ratios and 95% confidence intervals for lung cancer risk associated with whole grain food consumption were estimated by Cox proportional hazards regression.
    RESULTS: During a median follow-up of 12.2 years, a total of 1,706 incident lung cancer events occurred, including 1,473 (86.3%) cases of non-small cell lung cancer (NSCLC) and 233 (13.7%) of small cell lung cancer (SCLC). After multivariate adjustment, comparing the highest quarter of consumption of whole grain foods to the lowest quarter, a 16% lower rate (HR 0.84, 95% CI 0.73-0.98) of lung cancer risks and a 17% lower rate (HR 0.83, 95% CI 0.69-0.98) for NSCLC were found, but no significant difference was shown for SCLC (HR 0.95, 95% CI 0.63-1.44). These results were consistently observed after a large range of subgroup and sensitivity analyses. A linear dose-response pattern was shown for lung cancer, NSCLC, and SCLC (P for non-linearity > 0.05).
    CONCLUSIONS: In this large prospective cohort study, whole grain food consumption was associated with reduced lung cancer and NSCLC. Our findings suggest a potential protective role of whole grain foods against lung cancer.
    Keywords:  Cohort study; Lung cancer; Non-small cell lung cancer; Small cell lung cancer; Whole grain foods
    DOI:  https://doi.org/10.1186/s12935-025-03634-z
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