The burden of overweight: Higher body mass index, but not vital exhaustion, is associated with higher DNA damage and lower DNA repair capacity

Fieres, Judy; Fischer, M.; Sauter, Christine; Moreno‐Villanueva, María; Bürkle, Alexander; Wirtz, Petra H.

doi:10.1016/j.dnarep.2022.103323

Cited by 10 publications

(6 citation statements)

References 58 publications

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“…Bankoglu et al demonstrated that obesity is directly related to DNA damage since bariatric surgery with weight reduction reduced chromosomal damage [ 48 ]. Importantly, Fieres et al described the association between BMI and a decrease in DNA repair activity [ 49 ]. Thus, all these studies show that MetS is a risk factor for DNA damage and genomic instability.…”

Section: Discussionmentioning

confidence: 99%

Chromosomal Aberrations and Oxidative Stress in Psoriatic Patients with and without Metabolic Syndrome

et al. 2022

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Psoriasis and metabolic syndrome (MetS), a common comorbidity of psoriasis, are associated with mild chronic systemic inflammation that increases oxidative stress and causes cell and tissue damage. At the cellular level, chromosomal and DNA damage has been documented, thus confirming their genotoxic effect. The main objective of our study was to show the genotoxic potential of chronic inflammation and determine whether the presence of both pathologies increases chromosomal damage compared to psoriasis alone and to evaluate whether there are correlations between selected parameters and chromosomal aberrations in patients with psoriasis and MetS psoriasis. Clinical examination (PASI score and MetS diagnostics according to National Cholesterol Education Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults; NCE/ATPIII criteria), biochemical analysis of blood samples (fasting glucose, total cholesterol, low density and high density lipoproteins; LDL, HDL, non-HDL, and triglycerides;TAG), DNA/RNA oxidative damage, and chromosomal aberration test were performed in 41 participants (20 patients with psoriasis without MetS and 21 with MetS and psoriasis). Our results showed that patients with psoriasis without metabolic syndrome (nonMetS) and psoriasis and MetS had a higher rate of chromosomal aberrations than the healthy population for which the limit of spontaneous, natural aberration was <2%. No significant differences in the aberration rate were found between the groups. However, a higher aberration rate (higher than 10%) and four numerical aberrations were documented only in the MetS group. We found no correlations between the number of chromosomal aberrations and the parameters tested except for the correlation between aberrations and HDL levels in nonMetS patients (rho 0.44; p < 0.02). Interestingly, in the MetS group, a higher number of chromosomal aberrations was documented in non-smokers compared to smokers. Data from our current study revealed an increased number of chromosomal aberrations in patients with psoriasis and MetS compared to the healthy population, especially in psoriasis with MetS, which could increase the genotoxic effect of inflammation and the risk of genomic instability, thus increasing the risk of carcinogenesis.

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Section: Discussionmentioning

confidence: 99%

Chromosomal Aberrations and Oxidative Stress in Psoriatic Patients with and without Metabolic Syndrome

et al. 2022

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“…The main adverse consequences of overweight and obesity are cardiovascular diseases, non-alcoholic fatty liver disease (NAFLD), diabetes, cancer, and some immunerelated disorders [2,3]. Overweight and obesity can be de ned as a chronic and excessive expansion of adipose tissue, partly due to a chronic imbalance between energy intake and expenditure due in part to environmental and genetic factors [4,5]. Overweight is de ned as having a body mass index (BMI) greater than 24.9 kg/m² while obesity is de ned as having a BMI greater than or equal to 30 kg/m².…”

Section: Introductionmentioning

confidence: 99%

Serum Trace Metallic Element of Copper is Associated with Overweight and Obesity

Yang,

Liu,

Feng

et al. 2024

Preprint

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The relationship between serum trace metallic elements and overweight and obesity is unclear, and few studies have evaluated the relationship between serum trace metal elements and overweight and obesity. Nine serum trace metallic elements of Ca, Cu, Fe, Mg, Mn, Mo, Se, V and Zn were detected in people with obesity and normal adults. Then 1865 adults from 2011–2016 cycles of National Health and Nutrition Examination Survey was included for a large sample analysis. Serum Cu is highly expressed in the people with obesity. The third quartile (Q3) (OR: 1.898, 95% CI: 1.173–3.071, P = 0.012) and fourth quartile (Q4) (OR: 2.047, 95% CI: 1.201–3.489, P = 0.011) of Cu were related to an increased likelihood of people with overweight and obesity. Subgroup analysis showed that high levels of serum Cu (OR: 1.011, 95% CI: 1.004–1.018, P = 0.002) were found may be a risk factor for overweight and obesity in females and in the 20–39 years old (OR: 1.010, 95% CI: 1.002–1.019, P = 0.020). The RCS models detect non-linear relationships between serum trace metallic elements and overweight and obesity. The study provides insights into the relationship between trace metallic elements and overweight and obesity, providing an opportunity for further investigation in this area.

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“…Mutations in either BRCA1 or BRCA2 cause a defect in DNA repair, which can lead to an accumulation of DNA damage and, consequently, tumorigenesis ( 23 , 24 ). Studies have linked obesity or metabolic syndrome to DNA damage, including in leukocytes ( 25 ), skeletal muscle ( 26 ), peripheral blood mononuclear cells ( 27 ), and pancreatic β cells ( 28 ), but no studies have examined the relationship between obesity and DNA damage in normal breast epithelial cells.…”

Section: Introductionmentioning

confidence: 99%

Obesity promotes breast epithelium DNA damage in women carrying a germline mutation in BRCA1 or BRCA2

et al. 2023

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Obesity, defined as a body mass index (BMI) ≥ 30, is an established risk factor for breast cancer among women in the general population after menopause. Whether elevated BMI is a risk factor for women with a germline mutation in BRCA1 or BRCA2 is less clear because of inconsistent findings from epidemiological studies and a lack of mechanistic studies in this population. Here, we show that DNA damage in normal breast epithelia of women carrying a BRCA mutation is positively correlated with BMI and with biomarkers of metabolic dysfunction. In addition, RNA sequencing showed obesity-associated alterations to the breast adipose microenvironment of BRCA mutation carriers, including activation of estrogen biosynthesis, which affected neighboring breast epithelial cells. In breast tissue explants cultured from women carrying a BRCA mutation, we found that blockade of estrogen biosynthesis or estrogen receptor activity decreased DNA damage. Additional obesity-associated factors, including leptin and insulin, increased DNA damage in human BRCA heterozygous epithelial cells, and inhibiting the signaling of these factors with a leptin-neutralizing antibody or PI3K inhibitor, respectively, decreased DNA damage. Furthermore, we show that increased adiposity was associated with mammary gland DNA damage and increased penetrance of mammary tumors in Brca1 +/− mice. Overall, our results provide mechanistic evidence in support of a link between elevated BMI and breast cancer development in BRCA mutation carriers. This suggests that maintaining a lower body weight or pharmacologically targeting estrogen or metabolic dysfunction may reduce the risk of breast cancer in this population.

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The burden of overweight: Higher body mass index, but not vital exhaustion, is associated with higher DNA damage and lower DNA repair capacity

Cited by 10 publications

References 58 publications

Chromosomal Aberrations and Oxidative Stress in Psoriatic Patients with and without Metabolic Syndrome

Chromosomal Aberrations and Oxidative Stress in Psoriatic Patients with and without Metabolic Syndrome

Serum Trace Metallic Element of Copper is Associated with Overweight and Obesity

Obesity promotes breast epithelium DNA damage in women carrying a germline mutation in BRCA1 or BRCA2

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