Biomarkers of psychological stress are associated with increased susceptibility to the development of breast and prostate cancer in BRCA1/2 mutation carriers.
| Title: | Biomarkers of psychological stress are associated with increased susceptibility to the development of breast and prostate cancer in BRCA1/2 mutation carriers. |
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| Authors: | Flaherty RL; School of Applied Sciences, University of Brighton, Moulsecoomb, Brighton, UK.; The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK.; Falcinelli M; School of Applied Sciences, University of Brighton, Moulsecoomb, Brighton, UK.; IFOM ETS, The AIRC Institute of Molecular Oncology, Milan, Italy.; Hesketh AR; School of Applied Sciences, University of Brighton, Moulsecoomb, Brighton, UK.; Patel BA; School of Applied Sciences, University of Brighton, Moulsecoomb, Brighton, UK.; Bancroft E; Oncogenetics Team, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Sutton, UK.; Page E; Oncogenetics Team, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Sutton, UK.; Eeles R; Oncogenetics Team, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Sutton, UK.; Flint MS; School of Applied Sciences, University of Brighton, Moulsecoomb, Brighton, UK. M.Flint@brighton.ac.uk. |
| Corporate Authors: | IMPACT Study Steering Committee and Collaborators |
| Source: | British journal of cancer [Br J Cancer] 2025 Sep; Vol. 133 (5), pp. 615-624. Date of Electronic Publication: 2025 Jul 02. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Nature Publishing Group on behalf of Cancer Research UK Country of Publication: England NLM ID: 0370635 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-1827 (Electronic) Linking ISSN: 00070920 NLM ISO Abbreviation: Br J Cancer Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2002- : London : Nature Publishing Group on behalf of Cancer Research UK; Original Publication: London, Lewis. |
| MeSH Terms: | Prostatic Neoplasms*/genetics ; Prostatic Neoplasms*/psychology ; Prostatic Neoplasms*/blood ; Breast Neoplasms*/genetics ; Breast Neoplasms*/psychology ; Breast Neoplasms*/blood ; Stress, Psychological*/blood ; Stress, Psychological*/genetics ; Stress, Psychological*/complications ; BRCA1 Protein*/genetics ; BRCA2 Protein*/genetics ; Genes, BRCA1*; Hydrocortisone/blood ; Deoxyguanosine/analogs & derivatives ; Deoxyguanosine/urine ; Humans ; Male ; Female ; DNA Damage ; 8-Hydroxy-2'-Deoxyguanosine ; Mutation ; Middle Aged ; Genetic Predisposition to Disease ; Retrospective Studies ; Adult ; Heterozygote ; Aged ; Biomarkers, Tumor ; DNA Repair |
| Abstract: | Background: Epidemiological studies have linked psychological stress with an increased risk of breast cancer, however few studies have linked stress hormone signalling to cancer initiation mechanistically. This may be particularly pertinent in populations already at risk due to mutations in the cancer predisposition genes BRCA1/2.; Methods: Here we employ BRCA1/2 knockdown in breast and prostate epithelial cells to examine the effects of the stress hormone cortisol on DNA damage and repair. We perform a retrospective analysis of plasma cortisol and urinary 8-OHdG in a female BRCA-mutation carriers cohort (n = 62) and validate our findings in a male cohort (n = 70).; Results: Cortisol promotes DNA damage in normal mammary epithelial cells, and in a BRCA-deficient setting, delays DNA repair. In female BRCA-mutation carriers higher plasma cortisol levels are associated with an increased risk of cancer. In a male BRCA-mutation cohort risk of prostate cancer was also significantly increased in those with higher cortisol levels. Urinary 8-OHdG, a biomarker of oxidative DNA damage, was also correlated with a risk of breast cancer and prostate cancer.; Conclusion: Taken together these findings demonstrate that psychological stress, through the induction of DNA damage by cortisol, may increase the cumulative risk of cancer in BRCA-mutation carriers.; (© 2025. The Author(s), under exclusive licence to Springer Nature Limited.) |
| Competing Interests: | Competing interests: Professor Rosalind Eeles has the following conflicts of interest to declare: Honoraria from GU-ASCO, Janssen, University of Chicago, Dana Farber Cancer Institute USA as a speaker. Educational honorarium from Bayer and Ipsen, member of external expert committee to Astra Zeneca UK and Member of Active Surveillance Movember Committee. She is a member of the SAB of Our Future Health. She undertakes private practice as a sole trader at The Royal Marsden NHS Foundation Trust and 90 Sloane Street SW1X 9PQ and 280 Kings Road SW3 4NX, London, UK. The remaining authors declare no competing interest. Ethical approval: The IMPACT study protocol was reviewed and approved by the West-Midlands Research and Ethics Committee in the UK (reference: 05/MRE07/25) and subsequently by each participating institution’s local committee. All participants provided written consent, and the study was performed in accordance with the Declaration of Helsinki. The clinical studies are coordinated by the Institute of Cancer Research, London, UK. This project represents independent research supported by The National Institute for Health Research (NIHR) Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. |
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| Grant Information: | C5047/A21332, C5047/A13232 and C5047/A17528 Cancer Research UK (CRUK); CEO13_2-002 United Kingdom PCUK_ Prostate Cancer UK |
| Substance Nomenclature: | WI4X0X7BPJ (Hydrocortisone); 0 (BRCA1 Protein); 88847-89-6 (8-Hydroxy-2'-Deoxyguanosine); 0 (BRCA2 Protein); 0 (BRCA1 protein, human); 0 (BRCA2 protein, human); G9481N71RO (Deoxyguanosine); 0 (Biomarkers, Tumor) |
| Entry Date(s): | Date Created: 20250702 Date Completed: 20250903 Latest Revision: 20250905 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC12405614 |
| DOI: | 10.1038/s41416-025-03085-3 |
| PMID: | 40603570 |
| Database: | MEDLINE |
Journal Article