Household Exposure to Paint and Petroleum Solvents, Chromosomal Translocations, and the Risk of Childhood Leukemia

BackgroundFew studies have examined the association between home use of solvents and paint and the risk of childhood leukemia.ObjectivesIn this case-control study, we examined whether the use of paint and petroleum solvents at home before birth and in early childhood influenced the risk of leukemia in children.MethodsWe based our analyses on 550 cases of acute lymphoblastic leukemia (ALL), 100 cases of acute myeloid leukemia (AML), and one or two controls per case individually matched for sex, age, Hispanic status, and race. We conducted further analyses by cytogenetic subtype. We used conditional logistic regression techniques to adjust for income.ResultsALL risk was significantly associated with paint exposure [odds ratio (OR) = 1.65; 95% confidence interval (CI), 1.26-2.15], with a higher risk observed when paint was used postnatally, by a person other than the mother, or frequently. The association was restricted to leukemia with translocations between chromosomes 12 and 21 (OR = 4.16; 95% CI, 1.66-10.4). We found no significant association between solvent use and ALL risk overall (OR = 1.15; 95% CI, 0.87-1.51) or for various cytogenetic subtypes, but we observed a significant association in the 2.0- to 5.9-year age group (OR = 1.55; 95% CI, 1.07-2.25). In contrast, a significant increased risk for AML was associated with solvent (OR = 2.54; 95% CI, 1.19-5.42) but not with paint exposure (OR = 0.64; 95% CI, 0.32-1.25).ConclusionsThe association of ALL risk with paint exposure was strong, consistent with a causal relationship, but further studies are needed to confirm the association of ALL and AML risk with solvent exposure

Morphological findings in frozen non-neoplastic kidney tissues of patients with kidney cancer from large-scale multicentric studies on renal cancer.

Funder: FP7 Ideas: European Research Council; doi: http://dx.doi.org/10.13039/100011199; Grant(s): 241669There are unexplained geographical variations in the incidence of kidney cancer with the high rates reported in Baltic countries, as well as eastern and central Europe. Having access to a large and well-annotated collection of "tumor/non-tumor" pairs of kidney cancer patients from the Czech Republic, Romania, Serbia, UK, and Russia, we aimed to analyze the morphology of non-neoplastic renal tissue in nephrectomy specimens. By applying digital pathology, we performed a microscopic examination of 1012 frozen non-neoplastic kidney tissues from patients with renal cell carcinoma. Four components of renal parenchyma were evaluated and scored for the intensity of interstitial inflammation and fibrosis, tubular atrophy, glomerulosclerosis, and arterial wall thickening, globally called chronic renal parenchymal changes. Moderate or severe changes were observed in 54 (5.3%) of patients with predominance of occurrence in Romania (OR = 2.67, CI 1.07-6.67) and Serbia (OR = 4.37, CI 1.20-15.96) in reference to those from Russia. Further adjustment for comorbidities, tumor characteristics, and stage did not change risk estimates. In multinomial regression model, relative probability of non-glomerular changes was 5.22 times higher for Romania and Serbia compared to Russia. Our findings show that the frequency of chronic renal parenchymal changes, with the predominance of chronic interstitial nephritis pattern, in kidney cancer patients varies by country, significantly more frequent in countries located in central and southeastern Europe where the incidence of kidney cancer has been reported to be moderate to high. The observed association between these pathological features and living in certain geographic areas requires a larger population-based study to confirm this association on a large scale

Haplotypes of DNA repair and cell cycle control genes, X-ray exposure, and risk of childhood acute lymphoblastic leukemia

[[abstract]]Background: Acute leukemias of childhood are a heterogeneous group of malignancies characterized by cytogenetic abnormalities, such as translocations and changes in ploidy. These abnormalities may be influenced by altered DNA repair and cell cycle control processes. Methods: We examined the association between childhood acute lymphoblastic leukemia (ALL) and 32 genes in DNA repair and cell cycle pathways using a haplotype-based approach, among 377 childhood ALL cases and 448 controls enrolled during 1995-2002. Results: We found that haplotypes in APEX1, BRCA2, ERCC2, and RAD51 were significantly associated with total ALL, while haplotypes in NBN and XRCC4, and CDKN2A were associated with structural and numerical change subtypes, respectively. In addition, we observed statistically significant interaction between exposure to 3 or more diagnostic X-rays and haplotypes of XRCC4 on risk of structural abnormality-positive childhood ALL. Conclusions: These results support a role of altered DNA repair and cell cycle processes in the risk of childhood ALL, and show that this genetic susceptibility can differ by cytogenetic subtype and may be modified by exposure to ionizing radiation. To our knowledge, our study is the first to broadly examine the DNA repair and cell cycle pathways using a haplotype approach in conjunction with X-ray exposures in childhood ALL risk. If confirmed, future studies are needed to identify specific functional SNPs in the regions of interest identified in this analysis

Household exposure to paint and petroleum solvents, chromosomal translocations, and the risk of childhood leukemia.

BackgroundFew studies have examined the association between home use of solvents and paint and the risk of childhood leukemia.ObjectivesIn this case-control study, we examined whether the use of paint and petroleum solvents at home before birth and in early childhood influenced the risk of leukemia in children.MethodsWe based our analyses on 550 cases of acute lymphoblastic leukemia (ALL), 100 cases of acute myeloid leukemia (AML), and one or two controls per case individually matched for sex, age, Hispanic status, and race. We conducted further analyses by cytogenetic subtype. We used conditional logistic regression techniques to adjust for income.ResultsALL risk was significantly associated with paint exposure [odds ratio (OR) = 1.65; 95% confidence interval (CI), 1.26-2.15], with a higher risk observed when paint was used postnatally, by a person other than the mother, or frequently. The association was restricted to leukemia with translocations between chromosomes 12 and 21 (OR = 4.16; 95% CI, 1.66-10.4). We found no significant association between solvent use and ALL risk overall (OR = 1.15; 95% CI, 0.87-1.51) or for various cytogenetic subtypes, but we observed a significant association in the 2.0- to 5.9-year age group (OR = 1.55; 95% CI, 1.07-2.25). In contrast, a significant increased risk for AML was associated with solvent (OR = 2.54; 95% CI, 1.19-5.42) but not with paint exposure (OR = 0.64; 95% CI, 0.32-1.25).ConclusionsThe association of ALL risk with paint exposure was strong, consistent with a causal relationship, but further studies are needed to confirm the association of ALL and AML risk with solvent exposure

In utero exposure to endocrine disrupting chemicals, micro-RNA profiles, and fetal growth: a pilot study protocol

Background: The developing fetus is particularly vulnerable to the effects of endocrine disrupting chemicals (EDCs). Molecular fingerprints of EDCs can be identified via microRNA (miRNA) expression profiles and may be etiologically implicated in the developmental origin of disease (DOHaD). Methods/design: This pilot study includes pregnant women at high risk (smoking at conception), and low risk (non-smoking at conception) for SGA birth (birthweight Expected impact of the study for Public Health: Results from this pilot study will inform the development of a larger cohort wide analysis, and will impact the current state of knowledge in the fields of public health, epigenetics, and the DOHaD

In utero exposure to endocrine disrupting chemicals, micro-RNA profiles, and fetal growth: a pilot study protocol

Background: The developing fetus is particularly vulnerable to the effects of endocrine disrupting chemicals (EDCs). Molecular fingerprints of EDCs can be identified via microRNA (miRNA) expression profiles and may be etiologically implicated in the developmental origin of disease (DOHaD). Methods/design: This pilot study includes pregnant women at high risk (smoking at conception), and low risk (non-smoking at conception) for SGA birth (birthweight<10th percentile for gestational age). We have randomly selected 12 mothers (3 high-risk SGA birth, 3 low-risk SGA birth, 3 high-risk non-SGA birth, 3 low-risk non-SGA birth), with EDC measurements from gestational week 17. All offspring are female. We aim to test the stability of our samples (maternal serum, cord blood, placenta tissue), observe the differential expression of miRNA profiles over time (gestational weeks 17, 25, 33, 37, birth), and study the consistency between maternal EDC measures and miRNA expression profiles across our repeated measures. Expected impact of the study for Public Health: Results from this pilot study will inform the development of a larger cohort wide analysis, and will impact the current state of knowledge in the fields of public health, epigenetics, and the DOHaD

Occupational exposure to vinyl chloride, acrylonitrile and styrene and lung cancer risk (europe).

Several industry-based cohort studies have addressed the risk of lung cancer following exposure to vinyl chloride, acrylonitrile and styrene, with inconsistent results and usually without smoking adjustment. These exposures are addressed here in a large case-control study with full adjustment for smoking. Almost 6000 subjects were included in a case-control study conducted in seven European countries. For each job they held, local experts assessed the exposure to a number of occupational agents, including vinyl chloride, acrylonitrile and styrene, on the basis of detailed occupational questionnaires. Information on tobacco consumption and other risk factors was also collected. The odds ratio (OR) for ever exposure to vinyl chloride was 1.05 (95% confidence interval, CI: 0.68-1.62) and a modest, non-significant increase in the risk of lung cancer was found in the highest exposed subgroup. The OR for ever exposure to acrylonitrile was 2.20 (95% CI: 1.11-4.36) with a positive dose-response relationship between estimated cumulative exposure and lung cancer risk. No association between exposure to styrene and lung cancer risk was found. In conclusion, we cannot exclude a weak association between occupational exposure to vinyl chloride and lung cancer risk. Exposure to acrylonitrile was associated in our study with risk of lung cancer. Exposure to styrene does not seem to increase lung cancer risk

Haplotypes of DNA repair and cell cycle control genes, X-ray exposure, and risk of childhood acute lymphoblastic leukemia.

BackgroundAcute leukemias of childhood are a heterogeneous group of malignancies characterized by cytogenetic abnormalities, such as translocations and changes in ploidy. These abnormalities may be influenced by altered DNA repair and cell cycle control processes.MethodsWe examined the association between childhood acute lymphoblastic leukemia (ALL) and 32 genes in DNA repair and cell cycle pathways using a haplotype-based approach, among 377 childhood ALL cases and 448 controls enrolled during 1995-2002.ResultsWe found that haplotypes in APEX1, BRCA2, ERCC2, and RAD51 were significantly associated with total ALL, while haplotypes in NBN and XRCC4, and CDKN2A were associated with structural and numerical change subtypes, respectively. In addition, we observed statistically significant interaction between exposure to 3 or more diagnostic X-rays and haplotypes of XRCC4 on risk of structural abnormality-positive childhood ALL.ConclusionsThese results support a role of altered DNA repair and cell cycle processes in the risk of childhood ALL, and show that this genetic susceptibility can differ by cytogenetic subtype and may be modified by exposure to ionizing radiation. To our knowledge, our study is the first to broadly examine the DNA repair and cell cycle pathways using a haplotype approach in conjunction with X-ray exposures in childhood ALL risk. If confirmed, future studies are needed to identify specific functional SNPs in the regions of interest identified in this analysis