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PART 1GSTM1 and GSTT1 Genetic Susceptibility and Interaction with Chemical Exposures in Childhood Acute Lymphoblastic Leukemia: A Systematic Review and Meta-analysis
Background:The glutathione s-transferase genes play an important role in the detoxification of carcinogenic substances，and null mutations of these genes are linked to increase in acute lymphoblastic leukemia (ALL) due to an increase in susceptibility to environmental exposures of toxins and carcinogens，and chemical exposures like tobacco smoke and pesticides are common carcinogenic substances that children could be vulnerable to as risk of developing childhood ALL.
Objectives:The aim of this study is to analyze the effect of glutathione s-transferase mu1 and theta1 genetic susceptibility and interaction of chemical pesticide and tobacco smoke exposures on childhood ALL.
Data collection and analysis:A total of 22 published case-controls were included in the meta-analysis of over forty thousandparticipants with 14974 cases and 25841 controls.
Main results:Overall，the meta-analysis of these studies showed increase risk of ALL among children (random-effect OR 1.36，95% CI 1.18-1.57). Subgroup analysis showed that the GSTM1 and GSTT1 null genotype has more increase association to childhood ALL (random-effect OR 1.36，95% CI 1.05-1.76)，and chemical pesticide in comparison with tobacco smoke exposures did have an increase association with childhood ALL (random-effect OR 1.40，95% CI 1.10-1.78)，(random-effect OR 1.38，95% CI 1.20-1.58) respectively.
Authors conclusions:in this study,the GSTM1 null genotype is significantly associated with susceptibility to childhood acute lymphoblastic leukemia in Asians，and chemical pesticides also showing increase associations. The GSTM1 and GSTT1 null genotypes show nointeraction with chemical pesticidesand tobacco smoke exposuresin childhood ALL.
PART 2Epidemiological Study of Environmental Exposures Associated with Childhood Acute Lymphoblastic Leukemia (ALL) and Occurrence in Henan Province.
Background:Acute lymphoblastic leukemia (ALL)，whichis described as the most occurring childhood malignant iscomplex，has multiple factors and is a cancerous type of disease with a diverse character and an ambiguous condition and cause of disease. Childhood ALL is characterized by cancerous stem cells in the blood and bone marrow where they multiply and grow quickly at a faster rate leaving little or no room for the normal cells. The B-cell ALL or precursor B is a predominant type of ALL diagnosed in approximately 85% of all children with the disease. Studies have investigated many environmental and chemical exposures that the most familiar type of substances which causes cancer in children and especially as a risk of childhood ALL. Tons of thousands of these carcinogenic substances have become a principal environmental issue in China and also in certain areas where their consumption，utilization and production are in abundant amount，greatly differs from various regions.
Aim:To understand the epidemiology of childhood acute lymphoblastic leukemia in Henan Province and association with child?s environmental exposures and parent?s occupational exposures.
Data collection and analysis:A case-control study was performed in 2017-2018 and eligible cases diagnosed with acute leukemia where contacted through their parents，of whom 200 were enrolled and 203 population controls were also incorporated into the study. The recruitment site for caseswas the First Affiliated Hospital of Zhengzhou University，pediatrics hematology department.
Cases were eligible as residence of any region from within the Henan province，were recently diagnosed with acute leukemia，and are of age ≤15 years. Of all the recruited cases 173 ALL and 27 AML are from 18cities in the Henan. Data collected was analyzed using the SPSS statistical software,withmultivariate logistic regression analysis to estimate the adjusted odds ratios (OR) and 95% confidence intervals (95 % CI) of the associations between ALL and independent variables with adjustment for potential confounders.
Main results:Our study shows that in this Han population，Geneticsand infections (p<0.0001，p= 0.02) has highly significant associationswith childhood ALL than other risk factors like environmental exposures and health statusof the children with disease. Childhood ALL is significantly associated with child?s exposures to secondhand smoke (SHS) with (p=0.02)，Ionizing radiation with (p<0.0001)，household solvents with (p <0.0001)，and parental occupational pesticides with (p <0.0001)，paints with (p=0.001)，and Benzene & arsenics with (p=0.002). Geographically the group of cities in the central region has the highest occurrence of childhood ALL，with exposures of parent?s occupational paints，benzene & arsenic substances，and child?s exposure to SHS and other parental hazards as increasing significant exposures with (OR 2.1，95%CI 0.96-4.53)，(OR 3.6，95%CI 1.36-9.40)，(OR 2.1，95%CI 0.89-4.87) and (OR 1.5，95%CI 0.44-5.31) respectively.
Conclusions:we conclude the evidences from our results that the male children at age range between 0-5years from cities like Zhengzhou，Kaifeng，Xuchang，Pingding Mount and Luohe in Henan Province are at seriously greater exposure risk of acuteleukemia especially childhood ALL. Also,parent?s occupational activities withindustrial exposures and the home or environment of the child is a contributing factor and a greater influencing risk of disease.
Background:The glutathione s-transferase genes play an important role in the detoxification of carcinogenic substances，and null mutations of these genes are linked to increase in acute lymphoblastic leukemia (ALL) due to an increase in susceptibility to environmental exposures of toxins and carcinogens，and chemical exposures like tobacco smoke and pesticides are common carcinogenic substances that children could be vulnerable to as risk of developing childhood ALL.
Objectives:The aim of this study is to analyze the effect of glutathione s-transferase mu1 and theta1 genetic susceptibility and interaction of chemical pesticide and tobacco smoke exposures on childhood ALL.
Data collection and analysis:A total of 22 published case-controls were included in the meta-analysis of over forty thousandparticipants with 14974 cases and 25841 controls.
Main results:Overall，the meta-analysis of these studies showed increase risk of ALL among children (random-effect OR 1.36，95% CI 1.18-1.57). Subgroup analysis showed that the GSTM1 and GSTT1 null genotype has more increase association to childhood ALL (random-effect OR 1.36，95% CI 1.05-1.76)，and chemical pesticide in comparison with tobacco smoke exposures did have an increase association with childhood ALL (random-effect OR 1.40，95% CI 1.10-1.78)，(random-effect OR 1.38，95% CI 1.20-1.58) respectively.
Authors conclusions:in this study,the GSTM1 null genotype is significantly associated with susceptibility to childhood acute lymphoblastic leukemia in Asians，and chemical pesticides also showing increase associations. The GSTM1 and GSTT1 null genotypes show nointeraction with chemical pesticidesand tobacco smoke exposuresin childhood ALL.
PART 2Epidemiological Study of Environmental Exposures Associated with Childhood Acute Lymphoblastic Leukemia (ALL) and Occurrence in Henan Province.
Background:Acute lymphoblastic leukemia (ALL)，whichis described as the most occurring childhood malignant iscomplex，has multiple factors and is a cancerous type of disease with a diverse character and an ambiguous condition and cause of disease. Childhood ALL is characterized by cancerous stem cells in the blood and bone marrow where they multiply and grow quickly at a faster rate leaving little or no room for the normal cells. The B-cell ALL or precursor B is a predominant type of ALL diagnosed in approximately 85% of all children with the disease. Studies have investigated many environmental and chemical exposures that the most familiar type of substances which causes cancer in children and especially as a risk of childhood ALL. Tons of thousands of these carcinogenic substances have become a principal environmental issue in China and also in certain areas where their consumption，utilization and production are in abundant amount，greatly differs from various regions.
Aim:To understand the epidemiology of childhood acute lymphoblastic leukemia in Henan Province and association with child?s environmental exposures and parent?s occupational exposures.
Data collection and analysis:A case-control study was performed in 2017-2018 and eligible cases diagnosed with acute leukemia where contacted through their parents，of whom 200 were enrolled and 203 population controls were also incorporated into the study. The recruitment site for caseswas the First Affiliated Hospital of Zhengzhou University，pediatrics hematology department.
Cases were eligible as residence of any region from within the Henan province，were recently diagnosed with acute leukemia，and are of age ≤15 years. Of all the recruited cases 173 ALL and 27 AML are from 18cities in the Henan. Data collected was analyzed using the SPSS statistical software,withmultivariate logistic regression analysis to estimate the adjusted odds ratios (OR) and 95% confidence intervals (95 % CI) of the associations between ALL and independent variables with adjustment for potential confounders.
Main results:Our study shows that in this Han population，Geneticsand infections (p<0.0001，p= 0.02) has highly significant associationswith childhood ALL than other risk factors like environmental exposures and health statusof the children with disease. Childhood ALL is significantly associated with child?s exposures to secondhand smoke (SHS) with (p=0.02)，Ionizing radiation with (p<0.0001)，household solvents with (p <0.0001)，and parental occupational pesticides with (p <0.0001)，paints with (p=0.001)，and Benzene & arsenics with (p=0.002). Geographically the group of cities in the central region has the highest occurrence of childhood ALL，with exposures of parent?s occupational paints，benzene & arsenic substances，and child?s exposure to SHS and other parental hazards as increasing significant exposures with (OR 2.1，95%CI 0.96-4.53)，(OR 3.6，95%CI 1.36-9.40)，(OR 2.1，95%CI 0.89-4.87) and (OR 1.5，95%CI 0.44-5.31) respectively.
Conclusions:we conclude the evidences from our results that the male children at age range between 0-5years from cities like Zhengzhou，Kaifeng，Xuchang，Pingding Mount and Luohe in Henan Province are at seriously greater exposure risk of acuteleukemia especially childhood ALL. Also,parent?s occupational activities withindustrial exposures and the home or environment of the child is a contributing factor and a greater influencing risk of disease.