Home paint exposures and risk of childhood acute lymphoblastic leukemia: findings from the Childhood Leukemia International Consortium.

PURPOSE: It has been suggested that home paint exposure increases the risk of childhood acute lymphoblastic leukemia (ALL). METHODS: We obtained individual level data from eight case-control studies participating in the Childhood Leukemia International Consortium. All studies had home paint exposure data (sometimes including lacquers and varnishes) for the pregnancy period with additional data for the 1-3-month period before conception in five, the year before conception in two, and the period after birth in four studies, respectively. Cytogenetic subtype data were available for some studies. Data were harmonized to a compatible format. Pooled analyses of individual data were undertaken using unconditional logistic regression. RESULTS: Based on 3,002 cases and 3,836 controls, the pooled odds ratio (OR) for home paint exposure in the 1-3 months before conception and risk of ALL was 1.54 [95% confidence interval (CI) 1.28, 1.85], while based on 1,160 cases and 1,641 controls for exposure in the year before conception, it was 1.00 (95% CI 0.86, 1.17). For exposure during pregnancy, using 4,382 cases and 5,747 controls, the pooled OR was 1.14 (95% CI 1.04, 1.25), and for exposure after birth, the OR was 1.22 (95% CI 1.07, 1.39), based on data from 1,962 cases and 2,973 controls. The risk was greater for certain cytogenetic subtypes and if someone other than the parents did the painting. CONCLUSIONS: Home paint exposure shortly before conception, during pregnancy, and/or after birth appeared to increase the risk of childhood ALL. It may be prudent to limit exposure during these periods.

Parental occupational paint exposure and risk of childhood leukemia in the offspring: findings from the Childhood Leukemia International Consortium.

PURPOSE: It has been suggested that parental occupational paint exposure around the time of conception or pregnancy increases the risk of childhood leukemia in the offspring. METHODS: We obtained individual level data from 13 case-control studies participating in the Childhood Leukemia International Consortium. Occupational data were harmonized to a compatible format. Meta-analyses of study-specific odds ratios (ORs) were undertaken, as well as pooled analyses of individual data using unconditional logistic regression. RESULTS: Using individual data from fathers of 8,185 cases and 14,210 controls, the pooled OR for paternal exposure around conception and risk of acute lymphoblastic leukemia (ALL) was 0.93 [95% confidence interval (CI) 0.76, 1.14]. Analysis of data from 8,156 ALL case mothers and 14,568 control mothers produced a pooled OR of 0.81 (95% CI 0.39, 1.68) for exposure during pregnancy. For acute myeloid leukemia (AML), the pooled ORs for paternal and maternal exposure were 0.96 (95% CI 0.65, 1.41) and 1.31 (95% CI 0.38, 4.47), respectively, based on data from 1,231 case and 11,392 control fathers and 1,329 case and 12,141 control mothers. Heterogeneity among the individual studies ranged from low to modest. CONCLUSIONS: Null findings for paternal exposure for both ALL and AML are consistent with previous reports. Despite the large sample size, results for maternal exposure to paints in pregnancy were based on small numbers of exposed. Overall, we found no evidence that parental occupational exposure to paints increases the risk of leukemia in the offspring, but further data on home exposure are needed.

Fertility treatments, congenital malformations, fetal loss, and childhood acute leukemia: the ESCALE study (SFCE).

BACKGROUND: This study investigated the relationships between childhood acute leukemia (AL) and selective maternal and birth characteristics, including congenital malformations and the use of fertility treatment, for which the literature remains scarce. PROCEDURE: The national registry-based case-control study ESCALE was carried out in France in 2003-2004. Population controls were frequency matched with cases on age and gender. Data were obtained from structured telephone questionnaires. Odds ratios (OR) and their 95% confidence intervals were estimated using unconditional regression models adjusted for potential confounders. RESULTS: In all, 764 cases of AL (648 lymphoblastic AL (acute lymphoblastic leukemia, ALL) and 101 myeloblastic AL) and 1,681 controls were included. The AL cases' mothers reported congenital malformations more frequently than the controls' mothers (OR = 1.5 [1.0-2.4]). ALL was significantly associated with the use of fertility treatment for the index pregnancy (OR = 1.9 [1.3-2.8]). In particular, ALL was associated with ovulation induction only (OR = 2.6 [1.6-4.3]), but not with in vitro fertilization (IVF, OR = 1.0 [0.4-2.3]) or artificial insemination (OR = 1.3 [0.5-3.9]). A positive association was also observed for the difficulty of becoming pregnant without fertility treatment (OR = 1.5 [1.0-2.1]). AL was positively associated with a history of voluntary abortion (OR = 1.4 [1.1-1.8]) but not with a history of spontaneous (OR = 0.8 [0.7-1.0]) or therapeutic (OR = 0.7 [0.5-1.1]) abortion. CONCLUSION: The results suggest that subfertility in itself and ovulation induction may be associated with ALL, and support a positive association with congenital malformations. The links with the various types of fertility drugs and the underlying causes of infertility need to be investigated further.

Folic acid supplementation, MTHFR and MTRR polymorphisms, and the risk of childhood leukemia: the ESCALE study (SFCE).

PURPOSE: Fetal folate deficiency may increase the risk of subsequent childhood acute leukemia (AL), since folates are required for DNA methylation, synthesis, and repair, but the literature remains scarce. This study tested the hypothesis that maternal folic acid supplementation before or during pregnancy reduces AL risk, accounting for the SNPs rs1801133 (C677T) and rs1801131 (A1298C) in MTHFR and rs1801394 (A66G) and rs1532268 (C524T) in MTRR, assumed to modify folate metabolism. METHODS: The nationwide registry-based case-control study, ESCALE, carried out in 2003-2004, included 764 AL cases and 1,681 controls frequency matched with the cases on age and gender. Information on folic acid supplementation was obtained by standardized telephone interview. The genotypes were obtained using high-throughput platforms and imputation for untyped polymorphisms. Odds ratios (OR) were estimated using unconditional regression models adjusted for potential confounders. RESULTS: AL was significantly inversely associated with maternal folic acid supplementation before and during pregnancy (OR = 0.4; 95 % confidence interval: [0.3-0.6]). MTHFR and MTRR genetic polymorphisms were not associated with AL. However, AL was positively associated with homozygosity for any of the MTHFR polymorphisms and carriership of both MTRR variant alleles (OR = 1.6 [0.9-3.1]). No interaction was observed between MTHFR, MTRR, and maternal folate supplementation. CONCLUSION: The study findings support the hypothesis that maternal folic acid supplementation may reduce the risk of childhood AL. The findings also suggest that the genotype homozygous for any of the MTHFR variants and carrying both MTRR variants could be a risk factor for AL.

Road traffic and childhood leukemia: the ESCALE study (SFCE).

BACKGROUND: Traffic is a source of environmental exposures, including benzene, which may be related to childhood leukemia. OBJECTIVES: A national registry-based case-control study [ESCALE (Etude Sur les Cancers et les Leucémies de l'Enfant, Study on Environmental and Genetic Risk Factors of Childhood Cancers and Leukemia)] carried out in France was used to assess the effect of exposure to road traffic exhaust fumes on the risk of childhood leukemia. METHODS: Over the study period, 2003-2004, 763 cases and 1,681 controls < 15 years old were included, and the controls were frequency matched with the cases on age and sex. The ESCALE data were collected by a standardized telephone interview of the mothers. Various indicators of exposure to traffic and pollution were determined using the geocoded addresses at the time of diagnosis for the cases and of interview for the controls. Indicators of the distance from, and density of, main roads and traffic nitrogen dioxide (NO(2)) concentrations derived from traffic emission data were used. Odds ratios (ORs) were estimated using unconditional regression models adjusted for potential confounders. RESULTS: Acute leukemia (AL) was significantly associated with estimates of traffic NO(2) concentration at the place of residence > 27.7 µg/m(3) compared with NO(2) concentration < 21.9 µg/m(3) [OR=1.2; confidence interval (CI), 1.0-1.5] and with the presence of a heavy-traffic road within 500 m compared with the absence of a heavy-traffic road in the same area (OR=2.0; 95% CI, 1.0-3.6). There was a significant association between AL and a high density of heavy-traffic roads within 500 m compared with the reference category with no heavy-traffic road within 500 m (OR=2.2; 95% CI, 1.1-4.2), with a significant positive linear trend of the association of AL with the total length of heavy-traffic road within 500 m. CONCLUSION: This study supports the hypothesis that living close to heavy-traffic roads may increase the risk of childhood leukemia.