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Journal ArticleDOI

Diabetes--increased risk for cancers through chromosomal aberrations?

01 Jan 2014-Asian Pacific Journal of Cancer Prevention (Asian Pac J Cancer Prev)-Vol. 15, Iss: 11, pp 4571-4573
TL;DR: There was a significant increase in chromosomal aberration frequency in diabetic patient groups who are exposed to smoking and alcohol than that of normal diabetic groups (T1DM and T2DM), which may contribute to an increased risk for cancer.
Abstract: Diabetes, a comprehensive genetic disease, is principally due to the deregulation of glucose levels in the blood. In addition to contemporary epidemiological studies, systematic substantiation suggests that long-term diabetes leads to cancers due to a variety of reasons. In this study, blood samples were collected with informed consent from confirmed type I diabetic (T1DM, n=25) and type II Diabetic patients (T2DM, n=25) with equal numbers of controls. Further depending on the lifestyle habits they were subdivided into smokers/non-smokers and alcoholics/non-alcoholics. Chromosomal assays were performed for these cases and it was found that there was a significant increase in chromosomal aberration frequency in diabetic patient groups who are exposed to smoking and alcohol than that of normal diabetic groups (T1DM and T2DM). On the other hand, patient groups who were non-smoking and non-alcoholics also showed higher chromosomal aberrations when compared to that of controls. While the mechanisms for these increased chromosomal aberrations in diabetic groups are not clear, they may be due to increased oxidative stress leading to oxidative damage and resulting in genomic instability, which in turn may contribute to an increased risk for cancer.
Citations
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Journal ArticleDOI
TL;DR: This review will explore data obtained in Drosophila revealing the existence of a connection between vitamin B6, DNA damage and diabetes, as flies in the past decade turned out to be a promising model also for metabolic diseases including diabetes.
Abstract: Pyridoxal 5’-phosphate (PLP), the active form of vitamin B6, works as cofactor in numerous enzymatic reactions and it behaves as antioxidant molecule. PLP deficiency has been associated to many human pathologies including cancer and diabetes and the mechanism behind this connection is now becoming clearer. Improper intake of this vitamin increases the risk of many cancers; furthermore, PLP deprivation impairs insulin secretion in rats, whereas PLP supplementation prevents diabetic complications and improves gestational diabetes. Growing evidence shows that diabetes and cancer are correlated not only because they share same risk factors but also because diabetic patients have a higher risk of developing tumors, although the underlying mechanisms remain elusive. In this review, we will explore data obtained in Drosophila revealing the existence of a connection between vitamin B6, DNA damage and diabetes, as flies for the past decade turned out to be a promising model also for metabolic diseases including diabetes. We will focus on recent studies that revealed a specific role in maintaining chromosome integrity and glucose homeostasis for PLP and we will show that these aspects are correlated. In addition, we will discuss recent data identifying PLP as a putative linking factor between diabetes and cancer.

45 citations


Cites background from "Diabetes--increased risk for cancer..."

  • ...Consistently, oxidative damage and DNA strand breaks have been found in both type 1 and type 2 diabetic patients (Goodarzi et al., 2010; Tatsch et al., 2012; Anand et al., 2014)....

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Journal ArticleDOI
TL;DR: A statistically significant risk of breast cancer exists in women having elevated fasting blood glucose levels, corresponding to prediabetes and diabetes, among pre and postmenopausal ages, with comparatively greater effects in the premenopausal group.
Abstract: Background: There are several validated risk factors for breast cancer. However the legitimacy of elevated fasting blood glucose (FBG) is not well established. This study was designed to assess this parameter as a risk factor for breast cancer among pre- and post-menopausal women. Materials and Methods: This case-control study was conducted at Department of Biochemistry, University of Karachi from June 2010 to August 2014. Simple random sampling technique was used to collect data of study subjects comprising 175 diagnosed breast cancer patients with positive histopathology from Breast Clinic, surgical unit-1, Civil Hospital, Karachi and 175 healthy controls from various screening programs. Blood samples were analyzed for FBG and serum insulin. Results: FBG, HOMA-IR, systolic and diastolic blood pressure were significantly raised in breast cancer cases when compared to control subjects. Cases and controls were further categorized in to two groups using cutoff value of 110mg/dl to distinguish subjects into normal fasting glucose (<110mg/dl) and having impaired fasting glucose (≥110-≤125 mg/dl) or diabetes (≥126 mg/dl). Odds ratios were found to be 1.57, 2.15 and 1.17 in overall, pre-menopausal and post-menopausal groups, respectively. (all p < 0.05). Conclusions: A statistically significant risk of breast cancer exists in women having elevated fasting blood glucose levels, corresponding to prediabetes and diabetes, among pre and postmenopausal ages, with comparatively greater effects in the premenopausal group.

15 citations


Cites background from "Diabetes--increased risk for cancer..."

  • ...Another recent study (Anand et al., 2014) has found raised chromosomal abnormalities in diabetic subjects as compared to healthy controls, thus increasing he risk of cancer may be due to genomic instability....

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Journal ArticleDOI
TL;DR: The most prolonged and highest increases in the frequencies of cytogenetically instable cells were determined in the group of acute TBE patients with concomitant DM2 who were carriers of the genotype with inactive variants of both GSTM1 and GSTT1 glutathione-S-transferase genes.
Abstract: BACKGROUND: Tick-borne encephalitis (TBE) is an acute viral disease with activation of oxidative stress and increasing in cytogenetic instability. Clinical symptoms of infectious diseases usually more severe in patients with type 2 diabetes mellitus (DM2), especially in the case of burden in the genotype of mutant variants of glutathione-S-transferase genes GSTM1 and GSTT1. AIMS: The aim of this study was to study the dynamics of the frequency of micronucleated cells in patients with acute TBE with concomitant DM2, depending on the burden of active and inactive variants of glutathione-S-transferase genes (GSTM1 and GSTT1) in the patient’s genotype. MATERIALS AND METHODS: Totally, samples to make micronucleus assay were obtained from 138 patients with febrile illness of acute TBE, 64 of whom were diagnosed with concomitant DM2 (groups 3 and 4). As control groups, 57 healthy individuals (control 1) and 61 patients with DM2 (control 2) were examined. The samples of buccal cells for the micronucleus assay were repeatedly obtained from the individuals on the first day of admission, and also after 1 week, 1, 3 and 6 months. Polymerase chain reaction was used to analyze the variants of the GSTM1 and GSTT1 genes. RESULTS: On the first days of the disease, significant increases in the frequency of micronucleated buccal cells were determined in all TBE patients as compared to controls 1 and 2 (P<0.001). Significant increases in the frequency of micronucleated buccal cells was revealed in groups 3 and 4 of the TBE patients who were carriers of inactive variants of the GSTM1(0) and GSTT1(0) genes, as compared to the subgroup of TBE patients with active variants of these genes (P<0.001). In all subgroups of TBE patients with concomitant DM2, the frequencies of micronucleated cells were significantly higher than in the subgroups of TBE patients without DM2 (P<0.001). Study of the dynamics of the frequency of micronucleated buccal cells, as compared to the control, demonstrated that the highest and long-lasting (within 6 months) cytogenetical effects were maintained in the group of TBE patients with genotype GSTM1(0)/GSTT1 (0) and concomitant DM2. CONCLUSION: The most prolonged and highest increases in the frequencies of cytogenetically instable cells were determined in the group of acute TBE patients with concomitant DM2 who were carriers of the genotype with inactive variants of both GSTM1(0) and GSTT1(0) glutathione-S-transferase genes.

3 citations

Journal ArticleDOI
TL;DR: Data from the 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 therisk of carcinogenesis.
Abstract: 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.

1 citations

Journal ArticleDOI
TL;DR: Protein oxidative biomarker can serve as a therapeutic tool in the management of diabetes cases while increased chromosomal aberration may indicate an increased risk for cancer among diabetics.
Abstract: Background: The abundance of proteins in human system has made it a major target for glucose auto-oxidation. Likewise, chromosomal instability, describes an oxidative DNA damage that can be acceler...
References
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Journal ArticleDOI
TL;DR: A consensus statement of experts assembled jointly by the American Diabetes Association and the American Cancer Society reviews the state of science concerning the association between diabetes and cancer incidence or prognosis and whether diabetes treatments influence risk of cancer or cancer prognosis.
Abstract: Epidemiologic evidence suggests that cancer incidence is associated with diabetes as well as certain diabetes risk factors and diabetes treatments. This consensus statement of experts assembled jointly by the American Diabetes Association and the American Cancer Society reviews the state of science concerning 1) the association between diabetes and cancer incidence or prognosis, 2) risk factors common to both diabetes and cancer, 3) possible biologic links between diabetes and cancer risk, and 4) whether diabetes treatments influence risk of cancer or cancer prognosis. In addition, key unanswered questions for future research are posed.

1,790 citations

Journal ArticleDOI
TL;DR: A consensus statement of experts assembled jointly by the American Diabetes Association and the American Cancer Society as discussed by the authors reviewed the state of science concerning the association between diabetes and cancer incidence or prognosis.
Abstract: Epidemiologic evidence suggests that cancer incidence is associated with diabetes as well as certain diabetes risk factors and treatments. This consensus statement of experts assembled jointly by the American Diabetes Association and the American Cancer Society reviews the state of science concerning 1) the association between diabetes and cancer incidence or prognosis; 2) risk factors common to both diabetes and cancer; 3) possible biologic links between diabetes and cancer risk; and 4) whether diabetes treatments influence the risk of cancer or cancer prognosis. In addition, key unanswered questions for future research are posed.

1,546 citations

Journal ArticleDOI
TL;DR: The updated understanding of the antigluconeogenic action of met formin in the liver and the implications of the discoveries of metformin targets for the treatment of diabetes mellitus and cancer are discussed.
Abstract: Metformin has been the mainstay of therapy for diabetes mellitus for many years; however, the mechanistic aspects of metformin action remained ill-defined. Recent advances revealed that this drug, in addition to its glucose-lowering action, might be promising for specifically targeting metabolic differences between normal and abnormal metabolic signalling. The knowledge gained from dissecting the principal mechanisms by which metformin works can help us to develop novel treatments. The centre of metformin's mechanism of action is the alteration of the energy metabolism of the cell. Metformin exerts its prevailing, glucose-lowering effect by inhibiting hepatic gluconeogenesis and opposing the action of glucagon. The inhibition of mitochondrial complex I results in defective cAMP and protein kinase A signalling in response to glucagon. Stimulation of 5'-AMP-activated protein kinase, although dispensable for the glucose-lowering effect of metformin, confers insulin sensitivity, mainly by modulating lipid metabolism. Metformin might influence tumourigenesis, both indirectly, through the systemic reduction of insulin levels, and directly, via the induction of energetic stress; however, these effects require further investigation. Here, we discuss the updated understanding of the antigluconeogenic action of metformin in the liver and the implications of the discoveries of metformin targets for the treatment of diabetes mellitus and cancer.

972 citations

Journal ArticleDOI
TL;DR: Leukocytes were cultured from 0.2 ml of whole blood inoculated into 5 ml portions of a medium consisting of Eagle's basal amino acids and vitamins at double strength in Earle's balanced salt solution brought to pH 7.0 with 7.5% NaHCO3.
Abstract: Leukocytes were cultured from 0.2 ml of whole blood inoculated into 5 ml portions of a medium consisting of Eagle's basal amino acids and vitamins at double strength in Earle's balanced salt solution brought to pH 7.0 with 7.5% NaHCO3, and containing additives: glutamine, 2 mM; penicillin, 100 units/ml; streptomycin, 100 μg/ml; phenol red, 7 μg/ml; fetal or newborn agammaglobulin bovine serum, 15%; phytohemagglutinin M, 2%; and U.S.P. heparin sodium, 20,000 units/liter. Cultures were incubated in closed 60 × 28 mm screw-cap vials, in a gas phase initially of room air, for 3 days at 37 C, with colchicine to make 0.2 μg/ml added for the final 3-5 hr. After incubation, the cells were separated from the medium by centrifugation, the medium replaced by 0.075 M KCI plus 16 U.S.P. units/ml of heparin sodium at 37 C, cells resuspended and allowed to incubate 10 min. Removal of the hypotonic KCI was followed by fixation in methanol-acetic acid, 3:1 (changed twice), spreading cells on slides by the air-drying metho...

562 citations


"Diabetes--increased risk for cancer..." refers methods in this paper

  • ...Chromosome preparations were made by modified method of Hungerford, 1965....

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Journal ArticleDOI
TL;DR: The nature of ROS-induced damage on key cellular targets of oxidative stress is examined and evidence implicating ROS in clinically relevant, drug-related side effects including doxorubicin-induced cardiac damage, azidothymidine-induced myopathy, and cisplatin-induced ototoxicity is reviewed.
Abstract: Reactive oxygen species (ROS) are a byproduct of normal metabolism and have roles in cell signaling and homeostasis. Species include oxygen radicals and reactive nonradicals. Mechanisms exist that regulate cellular levels of ROS, as their reactive nature may otherwise cause damage to key cellular components including DNA, protein, and lipid. When the cellular antioxidant capacity is exceeded, oxidative stress can result. Pleiotropic deleterious effects of oxidative stress are observed in numerous disease states and are also implicated in a variety of drug-induced toxicities. In this paper, we examine the nature of ROS-induced damage on key cellular targets of oxidative stress. We also review evidence implicating ROS in clinically relevant, drug-related side effects including doxorubicin-induced cardiac damage, azidothymidine-induced myopathy, and cisplatin-induced ototoxicity.

542 citations


"Diabetes--increased risk for cancer..." refers background in this paper

  • ...Drug mediated oxidative stress is also known to be a major reason for tissue and organ toxicity (Damian et al., 2012), which may lead to various types of cancers....

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Trending Questions (1)
Is there specific genetic alterations associated with both diabetes and cancer?

The paper does not specifically mention any genetic alterations associated with both diabetes and cancer. The paper primarily focuses on the increased risk of cancer in diabetic patients due to chromosomal aberrations.