Antioxidant Properties of Zinc and Copper—Blood Zinc-to Copper-Ratio as a Marker of Cancer Risk BRCA1 Mutation Carriers
Abstract
:1. Introduction
2. Materials and Methods
2.1. Measurement of Blood Zinc and Copper Level
2.2. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Gudmundsdottir, K.; Ashworth, A. The Roles of BRCA1 and BRCA2 and Associated Proteins in the Maintenance of Genomic Stability. Oncogene 2006, 25, 5864–5874. [Google Scholar] [CrossRef] [PubMed]
- Yoshida, K.; Miki, Y. Role of BRCA1 and BRCA2 as Regulators of DNA Repair, Transcription, and Cell Cycle in Response to DNA Damage. Cancer Sci. 2004, 95, 866–871. [Google Scholar] [CrossRef] [PubMed]
- Long, D.T.; Joukov, V.; Budzowska, M.; Walter, J.C. BRCA1 Promotes Unloading of the CMG Helicase from a Stalled DNA Replication Fork. Mol. Cell 2014, 56, 174–185. [Google Scholar] [CrossRef] [PubMed]
- Schlacher, K.; Wu, H.; Jasin, M. A Distinct Replication Fork Protection Pathway Connects Fanconi Anemia Tumor Suppressors to RAD51-BRCA1/2. Cancer Cell 2012, 22, 106–116. [Google Scholar] [CrossRef] [PubMed]
- King, T.A.; Li, W.; Brogi, E.; Yee, C.J.; Gemignani, M.L.; Olvera, N.; Levine, D.A.; Norton, L.; Robson, M.E.; Offit, K.; et al. Heterogenic Loss of the Wild-Type BRCA Allele in Human Breast Tumorigenesis. Ann. Surg. Oncol. 2007, 14, 2510–2518. [Google Scholar] [CrossRef] [PubMed]
- Groelly, F.J.; Fawkes, M.; Dagg, R.A.; Blackford, A.N.; Tarsounas, M. Targeting DNA Damage Response Pathways in Cancer. Nat. Rev. Cancer 2023, 23, 78–94. [Google Scholar] [CrossRef] [PubMed]
- Kuchenbaecker, K.B.; Hopper, J.L.; Barnes, D.R.; Phillips, K.-A.; Mooij, T.M.; Roos-Blom, M.-J.; Jervis, S.; van Leeuwen, F.E.; Milne, R.L.; Andrieu, N.; et al. Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers. JAMA 2017, 317, 2402. [Google Scholar] [CrossRef]
- Iqbal, J.; Ragone, A.; Lubinski, J.; Lynch, H.T.; Moller, P.; Ghadirian, P.; Foulkes, W.D.; Armel, S.; Eisen, A.; Neuhausen, S.L.; et al. The Incidence of Pancreatic Cancer in BRCA1 and BRCA2 Mutation Carriers. Br. J. Cancer 2012, 107, 2005–2009. [Google Scholar] [CrossRef] [PubMed]
- Li, S.; Silvestri, V.; Leslie, G.; Rebbeck, T.R.; Neuhausen, S.L.; Hopper, J.L.; Nielsen, H.R.; Lee, A.; Yang, X.; McGuffog, L.; et al. Cancer Risks Associated With BRCA1 and BRCA2 Pathogenic Variants. J. Clin. Oncol. 2022, 40, 1529–1541. [Google Scholar] [CrossRef]
- Moran, A.; O’Hara, C.; Khan, S.; Shack, L.; Woodward, E.; Maher, E.R.; Lalloo, F.; Evans, D.G.R. Risk of Cancer Other than Breast or Ovarian in Individuals with BRCA1 and BRCA2 Mutations. Fam. Cancer 2012, 11, 235–242. [Google Scholar] [CrossRef]
- Phelan, C.M.; Iqbal, J.; Lynch, H.T.; Lubinski, J.; Gronwald, J.; Moller, P.; Ghadirian, P.; Foulkes, W.D.; Armel, S.; Eisen, A.; et al. Incidence of Colorectal Cancer in BRCA1 and BRCA2 Mutation Carriers: Results from a Follow-up Study. Br. J. Cancer 2014, 110, 530–534. [Google Scholar] [CrossRef] [PubMed]
- Friebel, T.M.; Domchek, S.M.; Rebbeck, T.R. Modifiers of Cancer Risk in BRCA1 and BRCA2 Mutation Carriers: A Systematic Review and Meta-Analysis. J. Natl. Cancer Inst. 2014, 106, dju091. [Google Scholar] [CrossRef] [PubMed]
- Li, X.; You, R.; Wang, X.; Liu, C.; Xu, Z.; Zhou, J.; Yu, B.; Xu, T.; Cai, H.; Zou, Q. Effectiveness of Prophylactic Surgeries in BRCA1 or BRCA2 Mutation Carriers: A Meta-Analysis and Systematic Review. Clin. Cancer Res. 2016, 22, 3971–3981. [Google Scholar] [CrossRef] [PubMed]
- Finch, A.; Metcalfe, K.; Lui, J.; Springate, C.; Demsky, R.; Armel, S.; Rosen, B.; Murphy, J.; Elit, L.; Sun, P.; et al. Breast and Ovarian Cancer Risk Perception after Prophylactic Salpingo-oophorectomy Due to an Inherited Mutation in the BRCA1 or BRCA2 Gene. Clin. Genet. 2009, 75, 220–224. [Google Scholar] [CrossRef] [PubMed]
- Milne, R.L.; Knight, J.A.; John, E.M.; Dite, G.S.; Balbuena, R.; Ziogas, A.; Andrulis, I.L.; West, D.W.; Li, F.P.; Southey, M.C.; et al. Oral Contraceptive Use and Risk of Early-Onset Breast Cancer in Carriers and Noncarriers of BRCA1 and BRCA2 Mutations. Cancer Epidemiol. Biomark. Prev. 2005, 14, 350–356. [Google Scholar] [CrossRef] [PubMed]
- Phillips, K.-A.; Milne, R.L.; Rookus, M.A.; Daly, M.B.; Antoniou, A.C.; Peock, S.; Frost, D.; Easton, D.F.; Ellis, S.; Friedlander, M.L.; et al. Tamoxifen and Risk of Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers. J. Clin. Oncol. 2013, 31, 3091–3099. [Google Scholar] [CrossRef] [PubMed]
- Pan, H.; He, Z.; Ling, L.; Ding, Q.; Chen, L.; Zha, X.; Zhou, W.; Liu, X.; Wang, S. Reproductive Factors and Breast Cancer Risk among BRCA1 or BRCA2 Mutation Carriers: Results from Ten Studies. Cancer Epidemiol. 2014, 38, 1–8. [Google Scholar] [CrossRef]
- Chang-Claude, J.; Andrieu, N.; Rookus, M.; Brohet, R.; Antoniou, A.C.; Peock, S.; Davidson, R.; Izatt, L.; Cole, T.; Noguès, C.; et al. Age at Menarche and Menopause and Breast Cancer Risk in the International BRCA1/2 Carrier Cohort Study. Cancer Epidemiol. Biomark. Prev. 2007, 16, 740–746. [Google Scholar] [CrossRef] [PubMed]
- Huber, D.; Seitz, S.; Kast, K.; Emons, G.; Ortmann, O. Use of Fertility Treatments in BRCA1/2 Mutation Carriers and Risk for Ovarian and Breast Cancer: A Systematic Review. Arch. Gynecol. Obstet. 2020, 302, 715–720. [Google Scholar] [CrossRef]
- Friedenson, B. Inflammation Targets Specific Organs for Cancer in Carriers of BRCA1/2 Pathway Mutations. Nat. Preced. 2010. [Google Scholar] [CrossRef]
- Nkondjock, A.; Ghadirian, P.; Kotsopoulos, J.; Lubinski, J.; Lynch, H.; Kim-Sing, C.; Horsman, D.; Rosen, B.; Isaacs, C.; Weber, B.; et al. Coffee Consumption and Breast Cancer Risk among BRCA1 and BRCA2 Mutation Carriers. Int. J. Cancer 2006, 118, 103–107. [Google Scholar] [CrossRef] [PubMed]
- Nkondjock, A.; Robidoux, A.; Paredes, Y.; Narod, S.A.; Ghadirian, P. Diet, Lifestyle and BRCA-Related Breast Cancer Risk among French-Canadians. Breast Cancer Res. Treat. 2006, 98, 285–294. [Google Scholar] [CrossRef] [PubMed]
- Kast, K.; John, E.M.; Hopper, J.L.; Andrieu, N.; Noguès, C.; Mouret-Fourme, E.; Lasset, C.; Fricker, J.-P.; Berthet, P.; Mari, V.; et al. Associations of Height, Body Mass Index, and Weight Gain with Breast Cancer Risk in Carriers of a Pathogenic Variant in BRCA1 or BRCA2: The BRCA1 and BRCA2 Cohort Consortium. Breast Cancer Res. 2023, 25, 72. [Google Scholar] [CrossRef] [PubMed]
- Ghadirian, P.; Narod, S.; Fafard, E.; Costa, M.; Robidoux, A.; Nkondjock, A. Breast Cancer Risk in Relation to the Joint Effect of BRCA Mutations and Diet Diversity. Breast Cancer Res. Treat. 2009, 117, 417–422. [Google Scholar] [CrossRef] [PubMed]
- Kiljańczyk, A.; Matuszczak, M.; Marciniak, W.; Derkacz, R.; Stempa, K.; Baszuk, P.; Bryśkiewicz, M.; Lubiński, K.; Cybulski, C.; Dębniak, T.; et al. Blood Lead Level as Marker of Increased Risk of Ovarian Cancer in BRCA1 Carriers. Nutrients 2024, 16, 1370. [Google Scholar] [CrossRef]
- Kiljańczyk, A.; Matuszczak, M.; Marciniak, W.; Derkacz, R.; Stempa, K.; Baszuk, P.; Bryśkiewicz, M.; Cybulski, C.; Dębniak, T.; Gronwald, J.; et al. Blood Iodine as a Potential Marker of the Risk of Cancer in BRCA1 Carriers. Nutrients 2024, 16, 1788. [Google Scholar] [CrossRef]
- Matuszczak, M.; Kiljańczyk, A.; Marciniak, W.; Derkacz, R.; Stempa, K.; Baszuk, P.; Bryśkiewicz, M.; Sun, P.; Cheriyan, A.; Cybulski, C.; et al. Zinc and Its Antioxidant Properties: The Potential Use of Blood Zinc Levels as a Marker of Cancer Risk in BRCA1 Mutation Carriers. Antioxidants 2024, 13, 609. [Google Scholar] [CrossRef]
- Escobedo-Monge, M.F.; Barrado, E.; Parodi-Román, J.; Escobedo-Monge, M.A.; Torres-Hinojal, M.C.; Marugán-Miguelsanz, J.M. Copper/Zinc Ratio in Childhood and Adolescence: A Review. Metabolites 2023, 13, 82. [Google Scholar] [CrossRef]
- Malavolta, M.; Piacenza, F.; Basso, A.; Giacconi, R.; Costarelli, L.; Mocchegiani, E. Serum Copper to Zinc Ratio: Relationship with Aging and Health Status. Mech. Ageing Dev. 2015, 151, 93–100. [Google Scholar] [CrossRef]
- Klevay, L. Coronary Heart Disease: The Zinc/Copper Hypothesis. Am. J. Clin. Nutr. 1975, 28, 764–774. [Google Scholar] [CrossRef]
- Stepien, M.; Hughes, D.J.; Hybsier, S.; Bamia, C.; Tjønneland, A.; Overvad, K.; Affret, A.; His, M.; Boutron-Ruault, M.-C.; Katzke, V.; et al. Circulating Copper and Zinc Levels and Risk of Hepatobiliary Cancers in Europeans. Br. J. Cancer 2017, 116, 688–696. [Google Scholar] [CrossRef] [PubMed]
- Stepien, M.; Jenab, M.; Freisling, H.; Becker, N.-P.; Czuban, M.; Tjønneland, A.; Olsen, A.; Overvad, K.; Boutron-Ruault, M.-C.; Mancini, F.R.; et al. Pre-Diagnostic Copper and Zinc Biomarkers and Colorectal Cancer Risk in the European Prospective Investigation into Cancer and Nutrition Cohort. Carcinogenesis 2017, 38, 699–707. [Google Scholar] [CrossRef] [PubMed]
- Bengtsson, Y.; Demircan, K.; Vallon-Christersson, J.; Malmberg, M.; Saal, L.H.; Rydén, L.; Borg, Å.; Schomburg, L.; Sandsveden, M.; Manjer, J. Serum Copper, Zinc and Copper/Zinc Ratio in Relation to Survival after Breast Cancer Diagnosis: A Prospective Multicenter Cohort Study. Redox Biol. 2023, 63, 102728. [Google Scholar] [CrossRef] [PubMed]
- Lubiński, J.; Lener, M.R.; Marciniak, W.; Pietrzak, S.; Derkacz, R.; Cybulski, C.; Gronwald, J.; Dębniak, T.; Jakubowska, A.; Huzarski, T.; et al. Serum Essential Elements and Survival after Cancer Diagnosis. Nutrients 2023, 15, 2611. [Google Scholar] [CrossRef]
- Pala, V.; Agnoli, C.; Cavalleri, A.; Rinaldi, S.; Orlandi, R.; Segrado, F.; Venturelli, E.; Vinceti, M.; Krogh, V.; Sieri, S. Prediagnostic Levels of Copper and Zinc and Breast Cancer Risk in the ORDET Cohort. Cancer Epidemiol. Biomark. Prev. 2022, 31, 1209–1215. [Google Scholar] [CrossRef]
- Prasad, A.S.; Beck, F.W.J.; Snell, D.C.; Kucuk, O. Zinc in Cancer Prevention. Nutr. Cancer 2009, 61, 879–887. [Google Scholar] [CrossRef]
- Prasad, A.S.; Bao, B.; Beck, F.W.J.; Kucuk, O.; Sarkar, F.H. Antioxidant Effect of Zinc in Humans. Free Radic. Biol. Med. 2004, 37, 1182–1190. [Google Scholar] [CrossRef]
- Patel, D.; Evanchuk, J.; Wang, R.; Dunbar, C.L.; Munhoz, J.; Field, C.J. Regulation of Immune Function in Healthy Adults: One-Stop Guide on the Role of Dietary Fatty Acids, Gut Microbiota-Derived Short Chain Fatty Acids, and Select Micronutrients in Combination with Physical Activity. Appl. Physiol. Nutr. Metab. 2023, 48, 554–568. [Google Scholar] [CrossRef]
- Faghfouri, A.H.; Baradaran, B.; Khabbazi, A.; Khaje Bishak, Y.; Zarezadeh, M.; Tavakoli-Rouzbehani, O.M.; Faghfuri, E.; Payahoo, L.; Alipour, M.; Alipour, B. Profiling Inflammatory Cytokines Following Zinc Supplementation: A Systematic Review and Meta-Analysis of Controlled Trials. Br. J. Nutr. 2021, 126, 1441–1450. [Google Scholar] [CrossRef]
- Harris, E.D. Copper as a Cofactor and Regulator of Copper, Zinc Superoxide Dismutase. J. Nutr. 1992, 122, 636–640. [Google Scholar] [CrossRef]
- Hellman, N.E.; Kono, S.; Mancini, G.M.; Hoogeboom, A.J.; de Jong, G.J.; Gitlin, J.D. Mechanisms of Copper Incorporation into Human Ceruloplasmin. J. Biol. Chem. 2002, 277, 46632–46638. [Google Scholar] [CrossRef] [PubMed]
- Ayala, A.; Muñoz, M.F.; Argüelles, S. Lipid Peroxidation: Production, Metabolism, and Signaling Mechanisms of Malondialdehyde and 4-Hydroxy-2-Nonenal. Oxid. Med. Cell. Longev. 2014, 2014, 360438. [Google Scholar] [CrossRef] [PubMed]
- Le Gal, K.; Schmidt, E.E.; Sayin, V.I. Cellular Redox Homeostasis. Antioxidants 2021, 10, 1377. [Google Scholar] [CrossRef] [PubMed]
- Pap, J.S.; Szywriel, Ł.; Rowińska-Żyrek, M.; Nikitin, K.; Fritsky, I.O.; Kozłowski, H. An Efficient Copper(III) Catalyst in the Four Electron Reduction of Molecular Oxygen by l-Ascorbic Acid. J. Mol. Catal. A Chem. 2011, 334, 77–82. [Google Scholar] [CrossRef]
- Iakovidis, I.; Delimaris, I.; Piperakis, S.M. Copper and Its Complexes in Medicine: A Biochemical Approach. Mol. Biol. Int. 2011, 2011, 594529. [Google Scholar] [CrossRef]
- Urso, E.; Maffia, M. Behind the Link between Copper and Angiogenesis: Established Mechanisms and an Overview on the Role of Vascular Copper Transport Systems. J. Vasc. Res. 2015, 52, 172–196. [Google Scholar] [CrossRef] [PubMed]
- Kothapalli, C.R.; Ramamurthi, A. Lysyl Oxidase Enhances Elastin Synthesis and Matrix Formation by Vascular Smooth Muscle Cells. J. Tissue Eng. Regen. Med. 2009, 3, 655–661. [Google Scholar] [CrossRef]
- Cox, T.R.; Erler, J.T. Remodeling and Homeostasis of the Extracellular Matrix: Implications for Fibrotic Diseases and Cancer. Dis. Model Mech. 2011, 4, 165–178. [Google Scholar] [CrossRef]
- Cheng, F.; Peng, G.; Lu, Y.; Wang, K.; Ju, Q.; Ju, Y.; Ouyang, M. Relationship between Copper and Immunity: The Potential Role of Copper in Tumor Immunity. Front. Oncol. 2022, 12, 1019153. [Google Scholar] [CrossRef]
- Osredkar, J. Copper and Zinc, Biological Role and Significance of Copper/Zinc Imbalance. J. Clin. Toxicol. 2011, S3, 1–18. [Google Scholar] [CrossRef]
- Gurer-Orhan, H.; Ince, E.; Konyar, D.; Saso, L.; Suzen, S. The Role of Oxidative Stress Modulators in Breast Cancer. Curr. Med. Chem. 2018, 25, 4084–4101. [Google Scholar] [CrossRef]
- Lee, J.D.; Cai, Q.; Shu, X.O.; Nechuta, S.J. The Role of Biomarkers of Oxidative Stress in Breast Cancer Risk and Prognosis: A Systematic Review of the Epidemiologic Literature. J. Womens Health 2017, 26, 467–482. [Google Scholar] [CrossRef] [PubMed]
- Mezzetti, A.; Pierdomenico, S.D.; Costantini, F.; Romano, F.; De Cesare, D.; Cuccurullo, F.; Imbastaro, T.; Riario-Sforza, G.; Di Giacomo, F.; Zuliani, G.; et al. Copper/Zinc Ratio and Systemic Oxidant Load: Effect of Aging and Aging-Related Degenerative Diseases. Free Radic. Biol. Med. 1998, 25, 676–681. [Google Scholar] [CrossRef]
- Snezhkina, A.V.; Kudryavtseva, A.V.; Kardymon, O.L.; Savvateeva, M.V.; Melnikova, N.V.; Krasnov, G.S.; Dmitriev, A.A. ROS Generation and Antioxidant Defense Systems in Normal and Malignant Cells. Oxid. Med. Cell. Longev. 2019, 2019, 6175804. [Google Scholar] [CrossRef]
- Ishikawa, K.; Takenaga, K.; Akimoto, M.; Koshikawa, N.; Yamaguchi, A.; Imanishi, H.; Nakada, K.; Honma, Y.; Hayashi, J.-I. ROS-Generating Mitochondrial DNA Mutations Can Regulate Tumor Cell Metastasis. Science (1979) 2008, 320, 661–664. [Google Scholar] [CrossRef]
- Feng, Y.; Zeng, J.-W.; Ma, Q.; Zhang, S.; Tang, J.; Feng, J.-F. Serum Copper and Zinc Levels in Breast Cancer: A Meta-Analysis. J. Trace Elem. Med. Biol. 2020, 62, 126629. [Google Scholar] [CrossRef] [PubMed]
- Fischer, P.W.; Giroux, A.; L’Abbé, M.R. The Effect of Dietary Zinc on Intestinal Copper Absorption. Am. J. Clin. Nutr. 1981, 34, 1670–1675. [Google Scholar] [CrossRef] [PubMed]
- Roy, R.; Chun, J.; Powell, S.N. BRCA1 and BRCA2: Different Roles in a Common Pathway of Genome Protection. Nat. Rev. Cancer 2012, 12, 68–78. [Google Scholar] [CrossRef]
- Meric-Bernstam, F. Heterogenic Loss of BRCA in Breast Cancer: The “Two-Hit” Hypothesis Takes a Hit. Ann. Surg. Oncol. 2007, 14, 2428–2429. [Google Scholar] [CrossRef]
- Yi, Y.; Kang, H.; Bae, I. BRCA1 and Oxidative Stress. Cancers 2014, 6, 771–795. [Google Scholar] [CrossRef]
- Ingvarsson, S. Genomic Instability and Breast Cancer Progression. Cancer Genom. Proteom. 2006, 3, 137–146. [Google Scholar]
- Maxwell, K.N.; Wubbenhorst, B.; Wenz, B.M.; De Sloover, D.; Pluta, J.; Emery, L.; Barrett, A.; Kraya, A.A.; Anastopoulos, I.N.; Yu, S.; et al. BRCA Locus-Specific Loss of Heterozygosity in Germline BRCA1 and BRCA2 Carriers. Nat. Commun. 2017, 8, 319. [Google Scholar] [CrossRef] [PubMed]
- Martin, S.K.; McVey, M. BRCA1 Protects against Its Own Fragility. Mol. Cell 2022, 82, 3757–3759. [Google Scholar] [CrossRef] [PubMed]
- Hartman, A.-R.; Ford, J.M. BRCA1 and P53: Compensatory Roles in DNA Repair. J. Mol. Med. 2003, 81, 700–707. [Google Scholar] [CrossRef] [PubMed]
- Deng, C.-X. BRCA1: Cell Cycle Checkpoint, Genetic Instability, DNA Damage Response and Cancer Evolution. Nucleic Acids Res. 2006, 34, 1416–1426. [Google Scholar] [CrossRef]
- Wang, M.; Li, W.; Tomimatsu, N.; Yu, C.H.; Ji, J.-H.; Alejo, S.; Witus, S.R.; Alimbetov, D.; Fitzgerald, O.; Wu, B.; et al. Crucial Roles of the BRCA1-BARD1 E3 Ubiquitin Ligase Activity in Homology-Directed DNA Repair. Mol. Cell 2023, 83, 3679–3691.e8. [Google Scholar] [CrossRef]
- DiSilvestro, R.A. Influence of Hormones on Copper Metalloprotein Levels. In Trace Elements in Man and Animals 6; Springer: Boston, MA, USA, 1988; pp. 103–107. [Google Scholar] [CrossRef]
N = 989 | |
---|---|
Age at enrollment | |
<50 years | 775 (78.36%) |
≥50 years | 214 (21.64%) |
Smoking | |
never | 720 (72.80%) |
ever | 264 (26.69%) |
missing data | 5 (0.51%) |
Hormonal therapy | |
never | 720 (72.80%) |
ever | 263 (26,59%) |
missing data | 6 (0.61%) |
Oophorectomy | |
no | 413 (41,76%) |
yes | 576 (58,24%) |
missing data | 0 (0.00%) |
Oral Contraceptive use | |
never | 501 (50,66%) |
ever | 481 (48,64%) |
missing data | 7 (0,70%) |
Diabetes | |
no | 880 (88.98%) |
yes | 62 (6.27%) |
missing data | 47 (4.75%) |
Body Mass Index (kg/m2) | |
<18.5 | 56 (5.66%) |
18.5–24.9 | 553 (55.92%) |
25.0–29.9 | 237 (23.96%) |
≥30.0 | 95 (9.61%) |
missing data | 48 (4.85%) |
Dietary supplements usage | |
never | 500 (50.56%) |
ever | 489 (49.44%) |
New cancer site (n = 174) (by the first cancer) | |
breast | 122 (70.11%) |
ovarian | 29 (16.67%) |
bladder | 2 (1.15%) |
cervix | 3 (1.72%) |
colon | 2 (1.15%) |
kidney | 1 (0.57%) |
leukemia | 2 (1.15%) |
lung | 3 (1.72%) |
pancreas | 1 (0.57%) |
salivary gland | 1 (0.57%) |
sarcoma | 1 (0.57%) |
site unknown | 1 (0.57%) |
skin | 1 (0.57%) |
thyroid | 3 (1.72%) |
urothelial | 1 (0.57%) |
abdomen-CSU | 1 (0.57%) |
New Cancer Frequency | New Cancer Univariable COX Regression | New Cancer Multivariable COX Regression | |||||||
---|---|---|---|---|---|---|---|---|---|
Characteristic | Overall, N = 914 1 | 0, N = 763 1 | 1, N = 151 1 | HR 2 | 95% CI 2 | p-Value | HR 2 | 95% CI 2 | p-Value |
Zn/Cu ratio | |||||||||
II (reference): 6.38–16.03 (7.47) | 540 (59%) | 467 (61%) | 73 (48%) | — | — | — | — | ||
I: 0.00–6.37 (5.26) | 374 (41%) | 296 (39%) | 78 (52%) | 1.53 | 1.11, 2.11 | 0.009 | 1.48 | 1.07, 2.05 | 0.017 |
Year of birth | |||||||||
≤1965 | 233 (25%) | 181 (24%) | 52 (34%) | — | — | — | — | ||
>1985 | 136 (15%) | 129 (17%) | 7 (4.6%) | 0.27 | 0.12, 0.59 | 0.001 | 0.27 | 0.09, 0.85 | 0.025 |
1965–1975 | 228 (25%) | 188 (25%) | 40 (26%) | 0.79 | 0.52, 1.19 | 0.3 | 0.88 | 0.44, 1.78 | 0.7 |
1975–1985 | 317 (35%) | 265 (35%) | 52 (34%) | 0.76 | 0.52, 1.11 | 0.2 | 0.80 | 0.33, 1.95 | 0.6 |
Age of blood draw | |||||||||
≤40 | 548 (60%) | 471 (62%) | 77 (51%) | — | — | — | — | ||
>50 | 175 (19%) | 135 (18%) | 40 (26%) | 1.57 | 1.07, 2.30 | 0.022 | 1.20 | 0.49, 2.95 | 0.7 |
40–50 | 191 (21%) | 157 (21%) | 34 (23%) | 1.25 | 0.84, 1.88 | 0.3 | 1.00 | 0.54, 1.88 | >0.9 |
Oral contraception | |||||||||
no | 454 (50%) | 378 (50%) | 76 (50%) | — | — | — | — | ||
yes | 460 (50%) | 385 (50%) | 75 (50%) | 0.97 | 0.70, 1.33 | 0.8 | 1.08 | 0.76, 1.53 | 0.7 |
Hormonal replacement therapy | |||||||||
no | 659 (72%) | 547 (72%) | 112 (74%) | — | — | — | — | ||
yes | 255 (28%) | 216 (28%) | 39 (26%) | 0.78 | 0.54, 1.12 | 0.2 | 0.68 | 0.46, 1.00 | 0.050 |
Smoker | |||||||||
Never | 517 (57%) | 444 (58%) | 73 (48%) | — | — | — | — | ||
Current | 207 (23%) | 168 (22%) | 39 (26%) | 1.39 | 0.94, 2.05 | 0.10 | 1.34 | 0.91, 1.99 | 0.14 |
Former | 190 (21%) | 151 (20%) | 39 (26%) | 1.48 | 1.00, 2.18 | 0.050 | 1.41 | 0.95, 2.08 | 0.087 |
BMI | |||||||||
<18.5 | 539 (59%) | 455 (60%) | 84 (56%) | — | — | — | — | ||
18.5–25.0 (reference) | 54 (5.9%) | 44 (5.8%) | 10 (6.6%) | 1.18 | 0.61, 2.26 | 0.6 | 1.30 | 0.67, 2.52 | 0.4 |
≥30.0 | 92 (10%) | 75 (9.8%) | 17 (11%) | 1.29 | 0.77, 2.18 | 0.3 | 1.04 | 0.60, 1.78 | 0.9 |
25.0–30.0 | 229 (25%) | 189 (25%) | 40 (26%) | 1.12 | 0.77, 1.64 | 0.5 | 0.96 | 0.65, 1.43 | 0.8 |
Adnexectomy | |||||||||
no | 423 (46%) | 331 (43%) | 92 (61%) | ||||||
yes | 491 (54%) | 432 (57%) | 59 (39%) |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Matuszczak, M.; Kiljańczyk, A.; Marciniak, W.; Derkacz, R.; Stempa, K.; Baszuk, P.; Bryśkiewicz, M.; Cybulski, C.; Dębniak, T.; Gronwald, J.; et al. Antioxidant Properties of Zinc and Copper—Blood Zinc-to Copper-Ratio as a Marker of Cancer Risk BRCA1 Mutation Carriers. Antioxidants 2024, 13, 841. https://doi.org/10.3390/antiox13070841
Matuszczak M, Kiljańczyk A, Marciniak W, Derkacz R, Stempa K, Baszuk P, Bryśkiewicz M, Cybulski C, Dębniak T, Gronwald J, et al. Antioxidant Properties of Zinc and Copper—Blood Zinc-to Copper-Ratio as a Marker of Cancer Risk BRCA1 Mutation Carriers. Antioxidants. 2024; 13(7):841. https://doi.org/10.3390/antiox13070841
Chicago/Turabian StyleMatuszczak, Milena, Adam Kiljańczyk, Wojciech Marciniak, Róża Derkacz, Klaudia Stempa, Piotr Baszuk, Marta Bryśkiewicz, Cezary Cybulski, Tadeusz Dębniak, Jacek Gronwald, and et al. 2024. "Antioxidant Properties of Zinc and Copper—Blood Zinc-to Copper-Ratio as a Marker of Cancer Risk BRCA1 Mutation Carriers" Antioxidants 13, no. 7: 841. https://doi.org/10.3390/antiox13070841
APA StyleMatuszczak, M., Kiljańczyk, A., Marciniak, W., Derkacz, R., Stempa, K., Baszuk, P., Bryśkiewicz, M., Cybulski, C., Dębniak, T., Gronwald, J., Huzarski, T., Lener, M., Jakubowska, A., Szwiec, M., Stawicka-Niełacna, M., Godlewski, D., Prusaczyk, A., Jasiewicz, A., Kluz, T., ... Lubiński, J. (2024). Antioxidant Properties of Zinc and Copper—Blood Zinc-to Copper-Ratio as a Marker of Cancer Risk BRCA1 Mutation Carriers. Antioxidants, 13(7), 841. https://doi.org/10.3390/antiox13070841