Environmental Pollution and Risk of Childhood Cancer: A Scoping Review of Evidence from the Last Decade

The long-term effects of environmental pollution have been of concern as several pollutants are carcinogenic, potentially inducing a variety of cancers, including childhood cancer, which is a leading cause of death around the world and, thus, is a public health issue. The present scoping review aimed to update and summarize the available literature to detect specific environmental pollutants and their association with certain types of childhood cancer. Studies published from 2013 to 2023 regarding environmental pollution and childhood cancer were retrieved from the PubMed database. A total of 174 studies were eligible for this review and were analyzed. Our search strategy brought up most of the articles that evaluated air pollution (29%) and pesticides (28%). Indoor exposure to chemicals (11%), alcohol and tobacco use during pregnancy (16%), electromagnetic fields (12%), and radon (4%) were the subjects of less research. We found a particularly high percentage of positive associations between prenatal and postnatal exposure to indoor (84%) and outdoor (79%) air pollution, as well as to pesticides (82%), and childhood cancer. Positive associations were found between leukemia and pesticides and air pollution (33% and 27%); CNS tumors and neuroblastoma and pesticides (53% and 43%); and Wilms tumor and other rare cancers were found in association with air pollution (50%). Indoor air pollution was mostly reported in studies assessing several types of cancer (26%). Further studies are needed to investigate the mechanisms underlying the potential associations between indoor/outdoor air pollution and pesticide exposure with childhood cancer risk as more preventable measures could be taken

Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro

The evidence supporting the biological plausibility of the association of permethrin and malathion with hematological cancer is limited and contradictory; thus, further studies are needed. This study aimed to investigate whether in vitro exposure to 0.1 μM permethrin and malathion at 0, 24, 48 and 72 h after cell culture initiation induced changes in the gene expression and DNA methylation in mononuclear cells from bone marrow and peripheral blood (BMMCs, PBMCs). Both pesticides induced several gene expression modifications in both tissues. Through gene ontology analysis, we found that permethrin deregulates ion channels in PBMCs and BMMCs and that malathion alters genes coding proteins with nucleic acid binding capacity, which was also observed in PBMCs exposed to permethrin. Additionally, we found that both insecticides deregulate genes coding proteins with chemotaxis functions, ion channels, and cytokines. Several genes deregulated in this study are potentially associated with cancer onset and development, and some of them have been reported to be deregulated in hematological cancer. We found that permethrin does not induce DNA hypermethylation but can induce hypomethylation, and that malathion generated both types of events. Our results suggest that these pesticides have the potential to modify gene expression through changes in promoter DNA methylation and potentially through other mechanisms that should be investigated

Association of HMOX1 and NQO1 Polymorphisms with Metabolic Syndrome Components.

Metabolic syndrome (MetS) is among the most important public health problems worldwide, and is recognized as a major risk factor for various illnesses, including type 2 diabetes mellitus, obesity, and cardiovascular diseases. Recently, oxidative stress has been suggested as part of MetS aetiology. The heme oxygenase 1 (HMOX1) and NADH:quinone oxidoreductase 1 (NQO1) genes are crucial mediators of cellular defence against oxidative stress. In the present study, we analysed the associations of HMOX1 (GT)n and NQO1 C609T polymorphisms with MetS and its components. Our study population comprised 735 Mexican Mestizos unrelated volunteers recruited from different tertiary health institutions from Mexico City. In order to know the HMOX1 (GT)n and NQO1 C609T allele frequencies in Amerindians, we included a population of 241 Amerindian native speakers. Their clinical and demographic data were recorded. The HMOX1 (GT)n polymorphism was genotyped using PCR and fluorescence technology. NQO1 C609T polymorphism genotyping was performed using TaqMan probes. Short allele (<25 GT repeats) of the HMOX1 polymorphism was associated with high systolic and diastolic blood pressure, and the T allele of the NQO1 C609T polymorphism was associated with increased triglyceride levels and decreased HDL-c levels, but only in individuals with MetS. This is the first study to analyse the association between MetS and genes involved in oxidative stress among Mexican Mestizos. Our data suggest that polymorphisms of HMOX1 and NQO1 genes are associated with a high risk of metabolic disorders, including high systolic and diastolic blood pressure, hypertriglyceridemia, and low HDL-c levels in Mexican Mestizo individuals

Characteristics of the Mexican Mestizo population.

<p>Age = average ± standard deviation.</p><p>HDL-c (< 40 men or < 50 mg/dL women),</p><p>Waist circumference (> 102 cm men or > 88 cm women).</p><p>Characteristics of the Mexican Mestizo population.</p

Associations of <i>NQO1</i> C609T polymorphisms with components of metabolic syndrome.

<p>Comparisons were made relative to the CC genotype and C allele.</p><p>^aQuantitative analysis: beta = −1.8, <i>P</i> = 0.0008. <i>P</i> values were adjusted by age, BMI, gender, medicament status, and Bonferroni correction.</p><p>Associations of <i>NQO1</i> C609T polymorphisms with components of metabolic syndrome.</p

Genotype and allele frequencies of <i>HMOX1</i> (GT)<i>n</i> polymorphism in Mexican Mestizo individuals.

<p>MetS = Metabolic syndrome. Data are presented as frequency (sample size).</p><p><i>P</i> values were adjusted by age, BMI, gender, medicament status,</p><p>and Bonferroni correction.</p><p>Genotype and allele frequencies of <i>HMOX1</i> (GT)<i>n</i> polymorphism in Mexican Mestizo individuals.</p

Associations of <i>HMOX1</i> (GT)<i>n</i> polymorphisms with components of metabolic syndrome.

<p>Comparisons were made relative to the LL genotype and L allele. Quantitative analysis, Beta value:</p><p>^<b>A</b> 1.6, <i>P</i> = 0.07.</p><p>^B 3.2, <i>P</i> = 0.009.</p><p>^<b>C</b>1.3, <i>P</i> = 0.03,</p><p>^<b>D</b> = 1.7, <i>P</i> = 0.04.</p><p><i>P</i> values were adjusted by age,</p><p>BMI, gender, medicament status, and Bonferroni correction.</p><p>Associations of <i>HMOX1</i> (GT)<i>n</i> polymorphisms with components of metabolic syndrome.</p

Frequency distribution of <i>HMOX1</i> (GT)<i>n</i> polymorphism.

<p>The number of repeats in Amerindian population (white bar, n = 241), and Mestizo population (black bar, n = 735) are shown as percentage.</p

Genotype and allele frequencies of <i>HMOX1</i> and <i>NQO1</i> polymorphisms in Amerindian and Mestizo populations.

<p>Data are presented as frequency (sample size).</p><p><i>P</i> values were adjusted by Bonferroni correction.</p><p>Genotype and allele frequencies of <i>HMOX1</i> and <i>NQO1</i> polymorphisms in Amerindian and Mestizo populations.</p

Expression of Ik6 and Ik8 Isoforms and Their Association with Relapse and Death in Mexican Children with Acute Lymphoblastic Leukemia

<div><p>Expression of the 6 and 8 dominant-negative Ikaros isoforms in pediatric patients with acute lymphoblastic leukemia has been associated with a high risk of relapse and death; due to these isoforms disrupting the differentiation and proliferation of lymphoid cells. The aim of this study was to know the frequency of Ik6 and Ik8 in 113 Mexican ALL-children treated within the National Popular Medical Insurance Program to determine whether there was an association with relapse-free survival, event-free survival and overall survival, and to assess its usefulness in the initial stratification of patients. The expression of these isoforms was analyzed using specific primer sets and nested RT-PCR. The detected transcripts were classified according to the isoforms’s sizes reported. A non-expected band of 300 bp from one patient was analyzed by sequencing. Twenty-six patients expressed Ik6 and/or Ik8 and one of them expressed a variant of Ik8 denominated Ik8-deleted. Although the presence of them was not statistically associated with lower relapse free survival (<i>p</i> = 0.432), event free survival (<i>p</i> = 0.667) or overall survival (<i>p</i> = 0.531), inferior overall survival was observed in patients that expressed these isoforms and showed high or standard risk by age and white blood-cell count at diagnosis. Of the 26 patients Ik6+ and/or Ik8+, 14 did not present adverse events; from them 6 were exclusively Ik6+ and/or Ik8+, and 8 were positive for the other Ikaros isoforms (Ik1, Ik2, Ik5, Ik3A, Ik4, Ik4A, Ik7). In the patients studied, the expression of Ik6 and Ik8 did not constitute an independent prognostic factor for relapse or death related to disease; therefore, they could not be used in the initial risk stratification.</p></div