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Genetic variability of oxidative stress and DNA repair genes associated with pre-treatment cancer-related fatigue in women with breast cancer

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Abstract

Purpose

Investigate potential relationships between pre-treatment cancer-related fatigue (CRF) in women with early-stage breast cancer and variation in genes involved with oxidative stress and DNA repair.

Methods

Investigated 39 functional and tagging single nucleotide polymorphisms (SNPs) in genes involved in oxidative stress (CAT, GPX1, SEPP1, SOD1, and SOD2) and DNA repair (ERCC2, ERCC3, ERCC5, and PARP1) in a sample (N = 219) that included n = 138 postmenopausal women diagnosed with early-stage breast cancer before initiation of therapy and n = 81 age- and education-matched healthy controls. Using the Profile of Mood States Fatigue/Inertia Subscale, fatigue occurrence and severity were evaluated in both groups. Regression analysis was used to independently identify significant SNPs for three outcomes: 1) any fatigue versus no fatigue, 2) clinically meaningful versus non-clinically meaningful fatigue, and 3) fatigue severity. Using a weighted multi-SNP method, genetic risk scores (GRS) were calculated for each participant, and GRS models were constructed for each outcome. Models were adjusted for age, pain, and symptoms of depression and anxiety.

Results

SEPP1rs3877899, ERCC2rs238406, ERCC2rs238416, ERCC2rs3916874, and ERCC3rs2134794 were associated with fatigue occurrence and had a significant GRS model (OR = 1.317, 95%CI [1.067, 1.675], P ≤ 0.05). One SNP, SOD2rs5746136, was significant for clinically meaningful fatigue; therefore, a GRS model could not be constructed. ERCC3rs4150407, ERCC3rs4150477, and ERCC3rs2134794 were associated with fatigue severity with a significant GRS model (b = 1.010, 95%CI [1.647, 4.577], R2 = 6.9%, P ≤ 0.01).

Conclusions

These results may contribute to identifying patients who are at risk of developing CRF. Oxidative stress and DNA repair biological pathways may be involved with CRF.

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Data Availability

The de-identified data that support the findings of this study are available from the authors and may require a data use agreement.

References

  1. Siegel RL, Miller KD, Fuchs HE, Jemal A (2022) Cancer statistics, 2022. CA Cancer J Clin 72:7–33. https://doi.org/10.3322/caac.21708

    Article  PubMed  Google Scholar 

  2. Esther Kim J-E, Dodd MJ, Aouizerat BE et al (2009) A review of the prevalence and impact of multiple symptoms in oncology patients. J Pain Symptom Manage 37:715–736. https://doi.org/10.1016/j.jpainsymman.2008.04.018

    Article  PubMed  Google Scholar 

  3. Schmidt ME, Scherer S, Wiskemann J, Steindorf K (2019) Return to work after breast cancer: The role of treatment-related side effects and potential impact on quality of life. Eur J Cancer Care (Engl) 28:e13051. https://doi.org/10.1111/ecc.13051

    Article  PubMed  Google Scholar 

  4. Abrahams HJG, Gielissen MFM, Verhagen CAHHVM, Knoop H (2018) The relationship of fatigue in breast cancer survivors with quality of life and factors to address in psychological interventions: A systematic review. Clin Psychol Rev 63:1–11. https://doi.org/10.1016/j.cpr.2018.05.004

    Article  CAS  PubMed  Google Scholar 

  5. Berger AM, Abernethy AP, Atkinson A et al (2010) Cancer-related fatigue. J Natl Compr Canc Netw 8:904–931. https://doi.org/10.6004/jnccn.2010.0067

    Article  PubMed  Google Scholar 

  6. Goedendorp MM, Jacobsen PB, Andrykowski MA (2016) Fatigue screening in breast cancer patients: identifying likely cases of cancer-related fatigue. Psychooncology 25:275–281. https://doi.org/10.1002/pon.3907

    Article  PubMed  Google Scholar 

  7. Hofman M, Ryan JL, Figueroa-Moseley CD et al (2007) Cancer-related fatigue: the scale of the problem. Oncologist 12(Suppl 1):4–10. https://doi.org/10.1634/theoncologist.12-S1-4

    Article  PubMed  Google Scholar 

  8. Jacobsen PB, Hann DM, Azzarello LM et al (1999) Fatigue in women receiving adjuvant chemotherapy for breast cancer: characteristics, course, and correlates. J Pain Symptom Manage 18:233–242. https://doi.org/10.1016/s0885-3924(99)00082-2

    Article  CAS  PubMed  Google Scholar 

  9. Li H, Sereika SM, Marsland AL et al (2019) Impact of chemotherapy on symptoms and symptom clusters in postmenopausal women with breast cancer prior to aromatase inhibitor therapy. J Clin Nurs 28:4560–4571. https://doi.org/10.1111/jocn.15047

    Article  PubMed  Google Scholar 

  10. Bower JE, Asher A, Garet D et al (2019) Testing a biobehavioral model of fatigue before adjuvant therapy in women with breast cancer. Cancer 125:633–641. https://doi.org/10.1002/cncr.31827

    Article  PubMed  Google Scholar 

  11. Ancoli-Israel S, Liu L, Rissling M et al (2014) Sleep, fatigue, depression, and circadian activity rhythms in women with breast cancer before and after treatment: a 1-year longitudinal study. Support Care Cancer 22:2535–2545. https://doi.org/10.1007/s00520-014-2204-5

    Article  PubMed  PubMed Central  Google Scholar 

  12. Hajj A, Chamoun R, Salameh P et al (2022) Fatigue in breast cancer patients on chemotherapy: a cross-sectional study exploring clinical, biological, and genetic factors. BMC Cancer 22:16. https://doi.org/10.1186/s12885-021-09072-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Tabrizi FM, Alizadeh S (2017) Cancer related fatigue in breast cancer survivors: in correlation to demographic factors. Maedica (Buchar) 12:106–111

    Google Scholar 

  14. Cheville AL, Shen T, Chang M, Basford JR (2013) Appropriateness of the treatment of fatigued patients with stage IV cancer. Support Care Cancer 21:229–233. https://doi.org/10.1007/s00520-012-1515-7

    Article  PubMed  Google Scholar 

  15. Sørensen HL, Schjølberg TK, Småstuen MC, Utne I (2020) Social support in early-stage breast cancer patients with fatigue. BMC Womens Health 20:243. https://doi.org/10.1186/s12905-020-01106-2

    Article  PubMed  PubMed Central  Google Scholar 

  16. Bower JE, Lamkin DM (2013) Inflammation and cancer-related fatigue: mechanisms, contributing factors, and treatment implications. Brain Behav Immun 30(Suppl):S48-57. https://doi.org/10.1016/j.bbi.2012.06.011

    Article  CAS  PubMed  Google Scholar 

  17. Saligan LN, Olson K, Filler K et al (2015) The biology of cancer-related fatigue: a review of the literature. Support Care Cancer 23:2461–2478. https://doi.org/10.1007/s00520-015-2763-0

    Article  PubMed  PubMed Central  Google Scholar 

  18. Swen M, Mann A, Paxton RJ, Dean LT (2017) Do Cancer-Related Fatigue and Physical Activity Vary by Age for Black Women With a History of Breast Cancer? Prev Chronic Dis 14:E122. https://doi.org/10.5888/pcd14.170128

    Article  PubMed  PubMed Central  Google Scholar 

  19. Banthia R, Malcarne VL, Ko CM et al (2009) Fatigued breast cancer survivors: the role of sleep quality, depressed mood, stage and age. Psychol Health 24:965–980. https://doi.org/10.1080/08870440802110831

    Article  PubMed  PubMed Central  Google Scholar 

  20. Bower JE (2019) The role of neuro-immune interactions in cancer-related fatigue: Biobehavioral risk factors and mechanisms. Cancer 125:353–364. https://doi.org/10.1002/cncr.31790

    Article  PubMed  Google Scholar 

  21. Chatterjee S (2016) Oxidative stress, inflammation, and disease Oxidative stress and biomaterials. Elsevier, pp 35–58

    Book  Google Scholar 

  22. Hayes JD, Dinkova-Kostova AT, Tew KD (2020) Oxidative stress in cancer. Cancer Cell 38:167–197. https://doi.org/10.1016/j.ccell.2020.06.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Paz MFCJ, Sobral ALP, Picada JN et al (2018) Persistent Increased Frequency of Genomic Instability in Women Diagnosed with Breast Cancer: Before, during, and after Treatments. Oxid Med Cell Longev 2018:2846819. https://doi.org/10.1155/2018/2846819

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Koleck TA, Bender CM, Sereika SM et al (2016) Polymorphisms in DNA repair and oxidative stress genes associated with pre-treatment cognitive function in breast cancer survivors: an exploratory study. Springerplus 5:422. https://doi.org/10.1186/s40064-016-2061-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Bender CM, Merriman JD, Sereika SM et al (2018) Trajectories of cognitive function and associated phenotypic and genotypic factors in breast cancer. Oncol Nurs Forum 45:308–326. https://doi.org/10.1188/18.ONF.308-326

    Article  PubMed  PubMed Central  Google Scholar 

  26. Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB (2010) Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med 49:1603–1616. https://doi.org/10.1016/j.freeradbiomed.2010.09.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Bender CM, Merriman JD, Gentry AL et al (2015) Patterns of change in cognitive function with anastrozole therapy. Cancer 121:2627–2636. https://doi.org/10.1002/cncr.29393

    Article  CAS  PubMed  Google Scholar 

  28. Meek PM, Nail LM, Barsevick A et al (2000) Psychometric testing of fatigue instruments for use with cancer patients. Nurs Res 49:181–190. https://doi.org/10.1097/00006199-200007000-00001

    Article  CAS  PubMed  Google Scholar 

  29. McNair D, Lorr M, Droppleman LF (1992) EdITS Manual for the Profile of Mood States. EdITS/Educational and Industrial Testing Service, San Diego, CA

    Google Scholar 

  30. Cleeland CS (1989) Measurement of pain by subjective report. In: Chapman CR, Loeser JD (eds) Advances in painresearch and therapy. Raven Press, New York, pp 391–403

    Google Scholar 

  31. Beck AT (1996) Beck Depression Inventory-II. The Psychological Corporation, San Antonio

    Google Scholar 

  32. Blackburn EH, Epel ES, Lin J (2015) Human telomere biology: A contributory and interactive factor in aging, disease risks, and protection. Science 350:1193–1198. https://doi.org/10.1126/science.aab3389

    Article  CAS  PubMed  Google Scholar 

  33. Friedberg EC (2001) How nucleotide excision repair protects against cancer. Nat Rev Cancer 1:22–33. https://doi.org/10.1038/35094000

    Article  CAS  PubMed  Google Scholar 

  34. Tirode F, Busso D, Coin F, Egly JM (1999) Reconstitution of the transcription factor TFIIH: assignment of functions for the three enzymatic subunits, XPB, XPD, and cdk7. Mol Cell 3:87–95. https://doi.org/10.1016/s1097-2765(00)80177-x

    Article  CAS  PubMed  Google Scholar 

  35. Rizza ERH, DiGiovanna JJ, Khan SG et al (2021) Xeroderma pigmentosum: A model for human premature aging. J Invest Dermatol 141:976–984. https://doi.org/10.1016/j.jid.2020.11.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Oetjen KA, Levoska MA, Tamura D et al (2020) Predisposition to hematologic malignancies in patients with xeroderma pigmentosum. Haematologica 105:e144–e146. https://doi.org/10.3324/haematol.2019.223370

    Article  PubMed  PubMed Central  Google Scholar 

  37. Cleaver JE, Brennan-Minnella AM, Swanson RA et al (2014) Mitochondrial reactive oxygen species are scavenged by Cockayne syndrome B protein in human fibroblasts without nuclear DNA damage. Proc Natl Acad Sci USA 111:13487–13492. https://doi.org/10.1073/pnas.1414135111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Hill KE, Wu S, Motley AK et al (2012) Production of selenoprotein P (Sepp1) by hepatocytes is central to selenium homeostasis. J Biol Chem 287:40414–40424. https://doi.org/10.1074/jbc.M112.421404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Gullett JM, Cohen RA, Yang GS et al (2019) Relationship of fatigue with cognitive performance in women with early-stage breast cancer over 2 years. Psychooncology 28:997–1003. https://doi.org/10.1002/pon.5028

    Article  PubMed  PubMed Central  Google Scholar 

  40. Juvet LK, Thune I, Elvsaas IKØ et al (2017) The effect of exercise on fatigue and physical functioning in breast cancer patients during and after treatment and at 6 months follow-up: A meta-analysis. Breast 33:166–177. https://doi.org/10.1016/j.breast.2017.04.003

    Article  CAS  PubMed  Google Scholar 

  41. Mishra SI, Scherer RW, Geigle PM, Berlanstein DR, Topaloglu O, Gotay CC, Snyder C (2012) Exercise interventions on health-related quality of life for cancer survivors. Cochrane Database Syst Rev 2012(8):CD007566. https://doi.org/10.1002/14651858.CD007566.pub2

  42. Sato S, Basse AL, Schönke M et al (2019) Time of exercise specifies the impact on muscle metabolic pathways and systemic energy homeostasis. Cell Metab 30:92-110.e4. https://doi.org/10.1016/j.cmet.2019.03.013

    Article  CAS  PubMed  Google Scholar 

  43. Kleckner AS, Kleckner IR, Culakova E et al (2022) Exploratory Analysis of Associations Between Whole Blood Mitochondrial Gene Expression and Cancer-Related Fatigue Among Breast Cancer Survivors. Nurs Res 71:411–417. https://doi.org/10.1097/NNR.0000000000000598

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors would like to acknowledge and thank the women who participated in this study.

Funding

This research was supported, in part, by the National Institute of Nursing Research (F31NR014590, T32NR009759), and National Cancer Institute (R01CA107408).

Author information

Authors and Affiliations

  1. Department of Health Promotion & Development, University of Pittsburgh School of Nursing, Pittsburgh, PA, USA

    Tara Davis, Theresa Koleck, Alex Conway & Yvette Conley

  2. Department of Health, and Community Systems, University of Pittsburgh School of Nursing, Pittsburgh, PA, USA

    Catherine Bender

  3. Department of Human Genetics, University of Pittsburgh School of Public Health, Pittsburgh, PA, USA

    Yvette Conley

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Contributions

Yvette Conley, and Catherine Bender contributed to study conception and design. Data preparation and analysis was performed by Tara Davis with statistical support from Theresa Koleck, and Alex Conway. Data analysis was reviewed by all authors. The first draft of the manuscript was written by Tara Davis and all authors commended on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Tara Davis.

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All procedures performed in this study, involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study was approved by the University of Pittsburgh Institutional Review Board. This study does not involve animal data or biological material.

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Informed consent was obtained from all individual participants included in this study.

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Davis, T., Koleck, T., Conway, A. et al. Genetic variability of oxidative stress and DNA repair genes associated with pre-treatment cancer-related fatigue in women with breast cancer. Support Care Cancer 31, 345 (2023). https://doi.org/10.1007/s00520-023-07816-1

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