Pre-diagnostic copper and zinc biomarkers and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort

Stępień, Magdalena; Jenab, Mazda; Freisling, Heinz; Becker, Niels-Peter; Czuban, Magdalena; Tjønneland, Anne; Olsen, Anja; Overvad, Kim; Boutron‐Ruault, Marie‐Christine; Mancini, Francesca Romana; Savoye, Isabelle; Katzke, Verena; Kühn, Tilman; Boeing, Heiner; Iqbal, Khalid; Trichopoulou, Antonia; Bamia, Christina; Orfanos, Philippos; Palli, Domenico; Sieri, Sabina; Tumino, Rosario; Naccarati, Alessio; Panico, Salvatore; Bueno-de-Mesquita, H. B.; Peeters, Petra H.M.; Weiderpass, Elisabete; Merino, Susana; Jakszyn, Paula; Sánchez, María‐José; Dorronsoro, Miren; Huerta, José María; Barricarte, Aurelio; Bodén, Stina; Guelpen, Behany van; Wareham, Nick; Khaw, Kay‐Tee; Bradbury, Kathryn E.; Cross, Amanda J.; Schomburg, Lutz; Hughes, David J.

doi:10.1093/carcin/bgx051

Cited by 104 publications

(86 citation statements)

References 40 publications

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“…Biomarkers using TEs attracted more attention following the reporting of evidence from previous studies on TEs and disease risk 41 . TEs have been used for differentiating to patients with and without cancer such as in breast cancer 42 , lung cancer 43 , prostate cancer 44 , and CRC 45 . Although TEs have attracted a lot of attention as potential cancer biomarkers, the cut-off values of the respective TEs have not been determined.…”

Section: Discussionmentioning

confidence: 99%

Delineating colorectal cancer distribution, interaction, and risk prediction by environmental risk factors and serum trace elements

Nawi

Chin

Mazlan

et al. 2020

Sci Rep

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The burden of colorectal cancer (CRC) is increasing worldwide especially in developing countries. This phenomenon may be attributable to lifestyle, dietary and environmental risk factors. We aimed to determine the level of 25 trace elements, their interaction with environmental risk factors, and subsequently develop a risk prediction model for CRC (RPM CRC). For the discovery phase, we used a hospital-based case–control study (CRC and non-CRC patients) and in the validation phase we analysed pre-symptomatic samples of CRC patients from The Malaysian Cohort Biobank. Information on the environmental risk factors were obtained and level of 25 trace elements measured using the ICP-MS method. CRC patients had lower Zn and Se levels but higher Li, Be, Al, Co, Cu, As, Cd, Rb, Ba, Hg, Tl, and Pb levels compared to non-CRC patients. The positive interaction between red meat intake ≥ 50 g/day and Co ≥ 4.77 µg/L (AP 0.97; 95% CI 0.91, 1.03) doubled the risk of CRC. A panel of 24 trace elements can predict simultaneously and accurate of high, moderate, and low risk of CRC (accuracy 100%, AUC 1.00). This study provides a new input on possible roles for various trace elements in CRC as well as using a panel of trace elements as a screening approach to CRC.

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Section: Discussionmentioning

confidence: 99%

Delineating colorectal cancer distribution, interaction, and risk prediction by environmental risk factors and serum trace elements

Nawi

Chin

Mazlan

et al. 2020

Sci Rep

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“…Data from case–control studies indicate higher copper levels, lower zinc levels, or higher copper/zinc ratio in patients with various cancers, including HCC . Two nested case–control studies within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort have observed that serum zinc levels were inversely and copper/zinc ratio was positively associated with risk of HCC and colorectal cancer, whereas higher serum copper levels were associated with increased risk of colorectal cancer, but not with risk of HCC . However, findings from the Shanghai Women's Health Study (SWHS) and the Shanghai Men's Health Study (SMHS) showed no association between dietary intake of copper and zinc and liver cancer risk .…”

Section: Introductionmentioning

confidence: 99%

“…[15][16][17][18][19] Two nested case-control studies within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort have observed that serum zinc levels were inversely and copper/zinc ratio was positively associated with risk of HCC and colorectal cancer, whereas higher serum copper levels were associated with increased risk of colorectal cancer, but not with risk of HCC. 20,21 However, findings from the Shanghai Women's Health Study (SWHS) and the Shanghai Men's Health Study (SMHS) showed no association between dietary intake of copper and zinc and liver cancer risk. 22 With regard to cancer progression, data from a French cohort study and the National Health and Nutrition Examination Survey (NHANES) have linked higher serum levels of copper and lower zinc with increased overall cancer mortality.…”

Section: Introductionmentioning

confidence: 99%

Serum copper and zinc levels at diagnosis and hepatocellular carcinoma survival in the Guangdong Liver Cancer Cohort

Fang

Chen

Wang

et al. 2019

Intl Journal of Cancer

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Copper and zinc are essential micronutrients, whose imbalance may be involved in the development and progression of cancer. However, the role of copper and/or zinc imbalance in the prognosis of hepatocellular carcinoma (HCC) is currently unclear. Our objective was to investigate the association between serum levels of copper, zinc and their ratio (copper/zinc) at diagnosis with HCC survival. We included 989 patients with incident HCC in this prospective cohort study, who were enrolled in the Guangdong Liver Cancer Cohort (GLCC) study within 30 days of diagnosis between September 2013 and February 2017. Serum copper and zinc were measured using inductively coupled plasma mass spectrometry. Primary outcomes were liver cancer‐specific survival (LCSS) and overall survival (OS). Cox proportional hazards models were used to calculate the multivariable hazard ratios (HRs) and 95% confidence interval (CI). Higher serum copper levels were strongly associated with worse LCSS (Q4 vs. Q1: HR = 1.87, 95% CI: 1.22–2.86; p < 0.01 for trend) and OS (Q4 vs. Q1: HR = 2.06, 95% CI: 1.36–3.11; p < 0.01 for trend). The calculated copper/zinc ratio was positively associated with LCSS (Q4 vs. Q1: HR = 1.31, 95% CI: 0.89–1.92; P = 0.04 for trend) and OS (Q4 vs. Q1: HR = 1.43, 95% CI: 0.99–2.08; P = 0.01 for trend). No overall associations were observed between serum zinc levels and LCSS or OS in the entire cohort. The results suggest that higher serum copper and copper in relation to zinc levels (i.e., higher copper/zinc ratio) may be associated with worse HCC survival, but serum zinc levels may be not associated with HCC survival.

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“…On the contrary, copper overload has been related to several health disorders including Wilson's, Parkinson's, Alzheimer's, and Huntington's diseases . Altered copper levels, and OS, have been associated with cancer progression; while some Cu(II) complexes exhibit anticancer properties . In addition, the role of synthetic copper nucleases on OD‐related processes is an emerging field of investigation .…”

Section: Introductionmentioning

confidence: 99%

Role of purines on the copper‐catalyzed oxidative damage in biological systems: Protection versus promotion

Castañeda‐Arriaga

Pérez-González

Álvarez-Idaboy

et al. 2017

Int J of Quantum Chemistry

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Oxidative damage to biomolecules is a serious health-threatening issue, which leads to the development of several diseases. Oxidative conditions are frequently catalyzed by metal ions. In this study, the role of purines in the copper-catalyzed oxidative stress was investigated using the density functional theory. The obtained results indicate that purines can have a dual behavior, acting as both protectors and promoters of oxidative stress. Their protection role arises from their known radical scavenging activity, as well as their ability to chelate Cu(II) leading to complexes that areto some extent-harder to reduce than free Cu(II). Conversely, their pro-oxidant role is a consequence of their reductant behavior, when deprotonated. Thus, the purines' anions can reduce Cu (II) to Cu(I), making the latter available to be involved in Fenton-like reactions. Consequently, mixtures of purines and Cu(II), at pHs where the fraction of deprotonated purines is rather significant, would yield • OH radicals. In turn, these very reactive radicals would damage biological targets such as lipids, proteins, and DNA.antioxidants, kinetics, pro-oxidants, rate constants, reaction mechanism 1 | I N TR ODU C TI ON Oxidative damage (OD) to biological targets such as lipids, proteins, and DNA is a serious health-threatening phenomenon. It has been held responsible, at least in part, for the onset and development of several diseases including cancer [1][2][3] ; rheumatoid arthritis [4][5][6] ; neurodegenerative disorders such as Parkinson's and Alzheimer's diseases, depression, multiple sclerosis, and memory loss [7][8][9][10][11][12][13] ; cardiovascular diseases such as atherosclerosis, ischemia, hypertension, cardiac hypertrophy, heart failure, and cardiomyopathy [14][15][16][17] ; as well as renal [18][19][20] and pulmonary failure. [21][22][23] OD arises as a consequence of a chemical imbalance between the production and consumption of oxidants, known as oxidative stress (OS). [24] One of the most damaging oxidants in biological systems is the hydroxyl radical ( • OH). It can be produced, in the presence of metal ions such as Fe(II) or Cu(I), by Fenton or Fenton-like reactions (M q 1 H 2 O 2 ! M q11 1OH -1 • OH). However, the most stable and abundant forms of these two metals, under physiological conditions, are Fe(III) and Cu(II). Thus, • OH production would actually involve the metal-catalyzed Haber-Weiss recombination (HWR). It comprises two chemical steps. The first one is the reduction of the metal ions (M q11 1 O •2 2 ! M q 1 3 O 2 ) and the second one is the Fenton reaction. Consequently, redox active metal ions are of particular interest for the chemistry of living systems. These ions cannot only bind to DNA, but they can also promote OD to DNA by mediating the production of oxygen reactive species (ROS). [25] In fact metal-mediated OD to DNA has become an important topic in metal toxicity and carcinogenesis. [26][27][28][29]

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Pre-diagnostic copper and zinc biomarkers and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort

Cited by 104 publications

References 40 publications

Delineating colorectal cancer distribution, interaction, and risk prediction by environmental risk factors and serum trace elements

Delineating colorectal cancer distribution, interaction, and risk prediction by environmental risk factors and serum trace elements

Serum copper and zinc levels at diagnosis and hepatocellular carcinoma survival in the Guangdong Liver Cancer Cohort

Role of purines on the copper‐catalyzed oxidative damage in biological systems: Protection versus promotion

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