Gene-environment interaction analysis of redox-related metals and genetic variants with plasma metabolic patterns in a general population from Spain: The Hortega Study

Gálvez-Fernández, Marta; Sánchez-Saez, Francisco; Domingo‐Relloso, Arce; Rodriguez-Hernandez, Zulema; Tarazona, Sonia; González-Marrachelli, Vannina; Grau-Pérez, María; Morales-Tatay, José Manuel; Amigó, Núria; García‐Barrera, Tamara; Gómez‐Ariza, José Luis; Chaves, F.J.; García‐García, A.; Melero, Rebeca; Téllez-Plaza, María; Martı́n-Escudero, Juan Carlos; Redón, Josep; Monleón, Daniel

doi:10.1016/j.redox.2022.102314

Cited by 10 publications

(9 citation statements)

References 158 publications

(212 reference statements)

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“…We revealed that a novel variant, rs1511625, presented both a significant metal QTL for Tl and an eQTL for ATP13A3 and thus serves as a colorectal cancer susceptibility variant. Similarly, recent studies have shown that several metals harbor strong interactions with genetic variants associated with biological pathways . Moreover, Engelken et al demonstrated the importance of regulatory variants for explaining population differences in trace element homeostasis and in the response to the elements .…”

Section: Discussionmentioning

confidence: 96%

Metal Exposure Promotes Colorectal Tumorigenesis via the Aberrant N⁶-Methyladenosine Modification of ATP13A3

Chen

et al. 2023

Environ. Sci. Technol.

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Element contamination, including that from heavy metals, is associated with gastrointestinal tumorigenesis, but the effects and mechanisms of crucial element exposure associated with colorectal cancer remain unclear. We profiled 56 elements by ICP-MS and used logistic regression, LASSO, BKMR, and GAM to identify colorectal cancer-relevant elements. A series of biochemical experiments were performed to demonstrate the cytotoxicity and the mechanisms of malignant transformation after metal exposure. Using an elementomics approach, we first found that the metal thallium (Tl) was positively correlated with many toxic metals and was associated with a significantly increased risk of colorectal cancer. Acute exposure to Tl induced cytotoxicity and cell death by accelerating the generation of reactive oxygen species and DNA damage. Chronic exposure to Tl led to the inhibition of cell death and thereby induced the malignant transformation of normal colon cells and xenograft tumor formation in nude mice. Furthermore, we describe the first identification of a significant metal quantitative trait locus for the novel colorectal cancer susceptibility locus rs1511625 near ATP13A3. Mechanistically, Tl increased the level of aberrant N 6 -methyladenosine (m 6 A) modification of ATP13A3 via the METLL3/ METTL14/ALKBH5-ATP13A3 axis to promote colorectal tumorigenesis. This study provides a basis for the development of public health strategies for reducing metal exposure among populations at high risk for colorectal cancer.

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Section: Discussionmentioning

confidence: 96%

Metal Exposure Promotes Colorectal Tumorigenesis via the Aberrant N⁶-Methyladenosine Modification of ATP13A3

Chen

et al. 2023

Environ. Sci. Technol.

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“…The study included a variety of heavy metals such as arsenic, with the correlation analyzed between heavy metal concentration and oxidative stress biomarkers by estimating metabolic principal components (mPC). It did not observe any association between serum arsenic levels with mPCs reflecting other lipoproteins, such as HDL and LDL except VLDL [ 48 ]. Consider the mechanism of arsenic exposure and cardiovascular disease, cardiotoxicity caused by As (III) or/and Sb might be concerning disturbing calcium homeostasis [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Linking the Low-Density Lipoprotein-Cholesterol (LDL) Level to Arsenic Acid, Dimethylarsinic, and Monomethylarsonic: Results from a National Population-Based Study from the NHANES, 2003–2020

Huang

2022

Nutrients

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Arsenic (As) contamination is a global public health problem. Elevated total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) are risk factors for cardiovascular diseases, but data on the association of urinary arsenic species’ level and LDL-C are limited. We performed an association analysis based on urinary arsenic species and blood TC and LDL-C in US adults. Methods: Urinary arsenic, arsenic acid (AA), dimethylarsinic (DMA), monomethylarsonic (MMA), TC, LDL-C, and other key covariates were obtained from the available National Health and Nutrition Examination Survey (NHANES) data from 2003 to 2020. Multiple linear regression analysis and generalized linear model are used to analyze linear and nonlinear relationships, respectively. Results: In total, 6633 adults aged 20 years were enrolled into the analysis. The median total urinary arsenic level was 7.86 µg/L. A positive association of urinary arsenic concentration quartiles was observed with TC (β: 2.42 95% CI 1.48, 3.36). The OR for TC of participants in the 80th versus 20th percentiles of urinary total arsenic was 1.34 (95% CI 1.13, 1.59). The OR for LDL-C of participants in the 80th versus 20th percentiles of urinary total arsenic was 1.36 (95% CI 1.15, 1.62). For speciated arsenics analysis, the OR for arsenic acid and TC was 1.35 (95% CI 1.02, 1.79), whereas the OR for DMA and LDL-L was 1.20 (95% CI 1.03, 1.41), and the OR for MMA and LDL-L was 1.30 (95% CI 1.11, 1.52). Conclusions: Urinary arsenic and arsenic species were positively associated with increased LDL-C concentration. Prevention of exposure to arsenic and arsenic species maybe helpful for the control of TC and LDL-C level in adults.

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“…Indeed, hIAPP can form oligomers and supramolecular structure named amyloid fibrils (Figure 2a-c) which toxicity toward pancreatic β-cells has been implicated in T2DM [5,13]. It has been shown that heavy metals could be associated to several human pathologies among which is T2DM [14]. However, recent study on a large-scale cohort could not find a direct link between lead and cadmium exposure and T2DM pathology [15].…”

Section: Hiapp Physiology and Pathologymentioning

confidence: 99%

Targeting hIAPP fibrillation: A new paradigm to prevent β-cell death?

Guillemain

Lacapère

Khemtémourian

2022

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Gene-environment interaction analysis of redox-related metals and genetic variants with plasma metabolic patterns in a general population from Spain: The Hortega Study

Cited by 10 publications

References 158 publications

Metal Exposure Promotes Colorectal Tumorigenesis via the Aberrant N⁶-Methyladenosine Modification of ATP13A3

Metal Exposure Promotes Colorectal Tumorigenesis via the Aberrant N⁶-Methyladenosine Modification of ATP13A3

Linking the Low-Density Lipoprotein-Cholesterol (LDL) Level to Arsenic Acid, Dimethylarsinic, and Monomethylarsonic: Results from a National Population-Based Study from the NHANES, 2003–2020

Targeting hIAPP fibrillation: A new paradigm to prevent β-cell death?

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Gene-environment interaction analysis of redox-related metals and genetic variants with plasma metabolic patterns in a general population from Spain: The Hortega Study

Cited by 10 publications

References 158 publications

Metal Exposure Promotes Colorectal Tumorigenesis via the Aberrant N6-Methyladenosine Modification of ATP13A3

Metal Exposure Promotes Colorectal Tumorigenesis via the Aberrant N6-Methyladenosine Modification of ATP13A3

Linking the Low-Density Lipoprotein-Cholesterol (LDL) Level to Arsenic Acid, Dimethylarsinic, and Monomethylarsonic: Results from a National Population-Based Study from the NHANES, 2003–2020

Targeting hIAPP fibrillation: A new paradigm to prevent β-cell death?

Contact Info

Product

Resources

About

Metal Exposure Promotes Colorectal Tumorigenesis via the Aberrant N⁶-Methyladenosine Modification of ATP13A3

Metal Exposure Promotes Colorectal Tumorigenesis via the Aberrant N⁶-Methyladenosine Modification of ATP13A3