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Linking birth records and cancer registry data from California, we conducted a population-based study with 23,419 cases and 87,593 matched controls born during 1978-2009 to investigate the relationship of parental age to risk of pediatric cancer. Compared with children born to mothers aged 20-24 years, those born to mothers in older age groups had a 13%-36% higher risk of pediatric cancer; the odds ratio for each 5-year increase in maternal age was 1.06 (95% confidence interval (CI): 1.04, 1.09). For cancer diagnosed in children in age groups 0-14 years and 15-19 years, the odds ratios for each 5-year increase in maternal age were 1.05 (95% CI: 1.02, 1.07) and 1.14 (95% CI: 1.09, 1.19), respectively. Having an older father also conferred an increased risk, with an odds ratio for each 5-year increase of 1.03 (95% CI: 1.02, 1.05) for cancer diagnosed at ages 0-19 years and 1.03 (95% CI: 1.02, 1.05) for cancer diagnosed at ages 0-14 years. While advancing maternal age increased risk of leukemia and central nervous system tumors, older paternal age was not associated with risk of either type. Both maternal and paternal older ages were associated with risk of lymphoma. In this large, population-based record-linkage study, advancing parental age, especially advancing maternal age, was associated with higher pediatric cancer risk, with variations across types of cancer. [ABSTRACT FROM AUTHOR]

The relationship of mode of delivery to risk of childhood acute lymphoblastic leukemia (ALL) is uncertain. After linking birth records and cancer registry data from California, we conducted a population-based case-control study to investigate the role of delivery by cesarean section (C-section) in the etiology of childhood ALL. This study included 5,081 cases and 18,927 matched controls born in 1978-2009; more detailed data were available on type of C-section (i.e., elective vs. emergency) for a subset of 1,552 cases and 5,688 controls. No association was observed between C-section overall and childhood ALL risk (<15 years of age), but elective C-section was associated with a significantly elevated risk of ALL (odds ratio (OR) = 1.17, 95% confidence interval (CI): 1.01, 1.36). At the peak ages of ALL incidence (2-4 years), C-section was associated with an 11 % higher risk of ALL (OR = 1.11, 95% CI: 1.01, 1.22) compared with vaginal delivery, and the magnitude of the association was larger for elective C-section (OR = 1.38, 95% CI: 1.11, 1.70). Emergency C-section was not associated with childhood ALL. Because of design features minimizing nonparticipation and inaccurate recall, this record linkage-based study is less prone to bias. Our results suggest that delivery by elective C-section was associated with a higher risk of childhood ALL, especially at the peak ages of incidence. It is important to evaluate possible mechanisms, because this potential risk factor is modifiable. [ABSTRACT FROM AUTHOR]

Previous studies on maternal nutrition and childhood leukaemia risk have focused on the role of specific nutrients such as folate and have not considered broader measures of diet quality, which may better capture intake of diverse nutrients known to impact fetal development. We examined the relationship between maternal diet quality before pregnancy, as summarised by a diet quality index, and risk of childhood acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML) in a case–control study in California. Dietary intake in the year before pregnancy was assessed using FFQ in 681 ALL cases, 103 AML cases and 1076 matched controls. Conditional logistic regression was used to estimate OR and 95 % CI for diet quality continuous score and quartiles (Q1–Q4). Higher maternal diet quality score was associated with reduced risk of ALL (OR 0·66; 95 % CI 0·47, 0·93 for Q4 v. Q1) and possibly AML (OR 0·42; 95 % CI 0·15, 1·15 for Q4 v. Q1). No single index component appeared to account for the association. The association of maternal diet quality with risk of ALL was stronger in children diagnosed under the age of 5 years and in children of women who did not report using vitamin supplements before pregnancy. These findings suggest that the joint effects of many dietary components may be important in influencing childhood leukaemia risk. [ABSTRACT FROM AUTHOR]

Purpose: Folate, vitamins B12 and B6, riboflavin, and methionine are critical nutrients for the one-carbon metabolism cycle involved in DNA synthesis and epigenetic processes. We examined the association between maternal intake of these nutrients before pregnancy and risk of childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) in a matched case-control study.Methods: Maternal dietary intake and vitamin supplement use in the year before pregnancy was assessed by food frequency questionnaire for 681 ALL cases, 103 AML cases, and 1076 controls. Principal component analysis was used to construct a variable representing combined nutrient intake, and conditional logistic regression estimated the odds ratio (OR) and 95% confidence interval (CI) for the association of ALL and AML with the principal component and each nutrient.Results: Higher maternal intake of one-carbon metabolism nutrients from food and supplements combined was associated with reduced risk of ALL (OR for one-unit change in the principal component = 0.91, CI 0.84-0.99) and possibly AML (OR for the principal component = 0.83, CI 0.66-1.04). When analyzed separately, intake of supplements high in these nutrients was associated with a reduced risk of ALL in children of Hispanic women only.Conclusions: In conclusion, these data suggest that higher maternal intake of one-carbon metabolism nutrients may reduce risk of childhood leukemia. [ABSTRACT FROM AUTHOR]

The associations between childhood acute lymphoblastic leukemia (ALL) and several proxies of early stimulation of the immune system, that is, day-care center attendance, birth order, maternally reported common infections in infancy, and breastfeeding, were investigated by using data from 11 case-control studies participating in the Childhood Leukemia International Consortium (enrollment period: 1980-2010). The sample included 7,399 ALL cases and 11,181 controls aged 2-14 years. The data were collected by questionnaires administered to the parents. Pooled odds ratios and 95% confidence intervals were estimated by unconditional logistic regression adjusted for age, sex, study, maternal education, and maternal age. Day-care center attendance in the first year of life was associated with a reduced risk of ALL (odds ratio = 0.77, 95% confidence interval: 0.71, 0.84), with a marked inverse trend with earlier age at start (P < 0.0001). An inverse association was also observed with breastfeeding duration of 6 months or more (odds ratio = 0.86, 95% confidence interval: 0.79, 0.94). No significant relationship with a history of common infections in infancy was observed even though the odds ratio was less than 1 for more than 3 infections. The findings of this large pooled analysis reinforce the hypothesis that day-care center attendance in infancy and prolonged breastfeeding are associated with a decreased risk of ALL. [ABSTRACT FROM AUTHOR]

Background: House dust is a major source of exposure to polybrominated diphenyl ethers (PBDEs), which are found at high levels in U.S. homes. Methods: We studied 167 acute lymphoblastic leukemia (ALL) cases 0–7 years of age and 214 birth certificate controls matched on date of birth, sex, and race/ethnicity from the Northern California Childhood Leukemia Study. In 2001–2007, we sampled carpets in the room where the child spent the most time while awake; we used a high-volume small-surface sampler or we took dust from the home vacuum. We measured concentrations of 14 PBDE congeners including penta (28, 47, 99, 100, 153, 154), octa (183, 196, 197, 203), and decaBDEs (206–209). Odds ratios (ORs) were calculated using logistic regression, adjusting for demographics, income, year of dust collection, and sampling method. Results: BDE-47, BDE-99, and BDE-209 were found at the highest concentrations (medians, 1,173, 1,579, and 938 ng/g, respectively). Comparing the highest to lowest quartile, we found no association with ALL for summed pentaBDEs (OR = 0.7; 95% CI: 0.4, 1.3), octaBDEs (OR = 1.3; 95% CI: 0.7, 2.3), or decaBDEs (OR = 1.0; 95% CI: 0.6, 1.8). Comparing homes in the highest concentration (nanograms per gram) tertile to those with no detections, we observed significantly increased ALL risk for BDE-196 (OR = 2.1; 95% CI: 1.1, 3.8), BDE-203 (OR = 2.0; 95% CI: 1.1, 3.6), BDE-206 (OR = 2.1; 95% CI: 1.1, 3.9), and BDE-207 (OR = 2.0; 95% CI: 1.03, 3.8). Conclusion: We found no association with ALL for common PBDEs, but we observed positive associations for specific octa and nonaBDEs. Additional studies with repeated sampling and biological measures would be informative. [ABSTRACT FROM AUTHOR]

Background: There is interest in using residential dust to estimate human exposure to environmental contaminants. Objectives: We aimed to characterize the sources of variability for polycyclic aromatic hydrocar­bons (PAHs) in residential dust and provide guidance for investigators who plan to use residential dust to assess exposure to PAHs. Methods: We collected repeat dust samples from 293 households in the Northern California Childhood Leukemia Study during two sampling rounds (from 2001 through 2007 and during 2010) using household vacuum cleaners, and measured 12 PAHs using gas chromatography-mass spectrometry. We used a random- and a mixed-effects model for each PAH to apportion observed variance into four components and to identify sources of variability. Results: Median concentrations for individual PAHs ranged from 10 to 190 ng/g of dust. For each PAH, total variance was apportioned into regional variability (1-9%), intraregional between-household variability (24-48%), within-household variability over time (41-57%), and within-sample analytical variability (2-33%). Regional differences in PAH dust levels were associated with estimated ambient air concentrations of PAH. Intraregional differences between households were associated with the residential construction date and the smoking habits of residents. For some PAHs, a decreasing time trend explained a modest fraction of the within-household variability; however, most of the within-household variability was unaccounted for by our mixed-effects models. Within-household differences between sampling rounds were largest when the interval between dust sample collections was at least 6 years in duration. Conclusions: Our findings indicate that it may be feasible to use residential dust for retrospective assessment of PAH exposures in studies of health effects. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Folate is involved in the one-carbon metabolism that plays an essential role in the synthesis, repair, and methylation of DNA. We examined whether child's germline genetic variation in the folate pathway is associated with childhood acute lymphoblastic leukemia (ALL), and whether periconception maternal folate and alcohol intake modify the risk.Methods: Seventy-six single nucleotide polymorphisms (SNPs), including 66 haplotype-tagging SNPs in 10 genes (CBS, DHFR, FOLH1, MTHFD1, MTHFR, MTR, MTRR, SHMT1, SLC19A1, and TYMS), were genotyped in 377 ALL cases and 448 controls. Log-additive associations between genotypes and ALL risk were adjusted for age, sex, Hispanic ethnicity (when appropriate), and maternal race.Results: Single and haplotype SNPs analyses showed statistically significant associations between SNPs located in (or adjacent to) CBS, MTRR, TYMS/ENOFS, and childhood ALL. Many regions of CBS were associated with childhood ALL in Hispanics and non-Hispanics (p < 0.01). Levels of maternal folate intake modified associations with SNPs in CBS, MTRR, and TYMS.Conclusion: Our data suggest the importance of genetic variability in the folate pathway and childhood ALL risk. [ABSTRACT FROM AUTHOR]

Background: The association between diagnostic X-ray exposures early in life and increased risk of childhood leukaemia remains unclear.Methods: This case-control study included children aged 0-14 years diagnosed with acute lymphoid leukaemia (ALL, n = 711) or acute myeloid leukaemia (AML, n = 116) from 1995 to 2008. Controls were randomly selected from the California birth registry and individually matched to cases with respect to date of birth, sex, Hispanic ethnicity and maternal race. Conditional logistic regression analyses were performed to assess whether ALL or AML was associated with self-reported child's X-rays after birth (post-natal), including number of X-rays, region of the body X-rayed and age at first X-ray, as well as maternal X-rays before and during pregnancy (preconception and prenatal).Results: After excluding X-rays in the year prior to diagnosis (reference date for matched controls), risk of ALL was elevated in children exposed to three or more post-natal X-rays [odds ratio (OR) = 1.85, 95% confidence interval (CI) 1.12-2.79]. For B-cell ALL specifically, any exposure (one or more X-rays) conferred increased risk (OR = 1.40, 95% CI 1.06-1.86). Region of the body exposed was not an independent risk factor in multivariable analyses. No associations were observed between number of post-natal X-rays and AML (OR = 1.05, 95% CI 0.90-1.22) or T-cell ALL (OR = 0.84, 95% CI 0.59-1.19). Prevalence of exposure to prenatal and preconception X-rays was low, and no associations with ALL or AML were observed.Conclusions: The results suggest that exposure to post-natal diagnostic X-rays is associated with increased risk of childhood ALL, specifically B-cell ALL, but not AML or T-cell ALL. Given the imprecise measures of self-reported X-ray exposure, the results of this analysis should be interpreted with caution and warrant further investigation. [ABSTRACT FROM AUTHOR]

BACKGROUND: Few studies have examined the association between home use of solvents and paint and the risk of childhood leukemia. OBJECTIVES: In 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. METHODS: We 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. RESULTS: ALL 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). CONCLUSIONS: The 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. [ABSTRACT FROM AUTHOR]

Workers in the meat industry are exposed to viruses that cause leukemia and lymphoma in cattle and chickens, and also to carcinogenic chemical agents. This case-control study, nested in a cohort of members of a meatcutters' union in Baltimore, Maryland, investigated whether occupational exposures are associated with death from tumors of the hemopoietic and lymphatic systems. Cases of these tumors represent all deaths which occurred in the cohort between 1949 and 1980. Excess risks of tumors of the hemopoietic and lymphatic systems were observed throughout the meat industry, except in meatpacking plants. Slaughtering activities involving heavy exposure to oncogenic viruses were strongly associated with these tumors, especially with lymphomas. Thus, elevated risks were observed for butchers who killed animals (odds ratio (OR) = 5.3, 95% confidence interval (CI) 1.0–27.0); workers in chicken-slaughtering plants (OR = 3.3, 95% CI 0.8–13.1); and workers in cattle/sheep/pig abattoirs (OR = 2.8, 95% CI 0.8–9.5). Among supermarket workers, wrapping meat (mainly a female activity) was associated with increased risk of tumors of the hemopoietic and lymphatic systems (OR = 3.8, 95% CI 1.0–14.3), with the odds of both lymphomas and tumors of the myeloid stem cell being elevated. On the other hand, meatcutting in supermarkets (almost exclusively a male activity) was associated with multiple myeloma; the odds ratio for men was 18.0 (95% CI 1.6–207.5), with no myeloma cases being recorded in women. These associations persisted after limited control for exposures outside the industry that have also been observed to be associated with excess risk, such as exposure to pesticides, working/living on pig farms, and exposure to X-rays. The findings provide evidence that workers in the meat industry may be at elevated risk of tumors of the hemopoietic and lymphatic systems. Further studies with larger sample sizes are needed to identify more conclusively which exposures play an etiologic role in the occurrence of the different histologic types of these tumors. Am J Epidemiol 1998;147;727–38. [ABSTRACT FROM PUBLISHER]

Purpose: Data from the Northern California Childhood Leukemia Study (NCCLS) were used to assess whether selection bias may explain the association between residential magnetic fields (assessed by wire codes) and childhood leukemia as previously observed in case-control studies. Methods: Wiring codes were calculated for participating cases, n = 310; and non-participating cases, n = 66; as well as for three control groups: first-choice participating, n = 174; first-choice non-participating, n = 252; and replacement (non-first choice participating controls), n = 220. Results: Participating controls tended to be of higher socioeconomic status than non-participating controls, and lower socioeconomic status was related to higher wire-codes. The odds ratio (OR) for developing childhood leukemia associated with high wire-codes was 1.18 (95% CI: 0.85, 1.64) when all cases were compared to all first-choice controls (participating and non-participating). The OR for developing childhood leukemia in the high current category was 1.43 (95% CI: 0.91, 2.26) when participating cases were compared to first-choice participating controls, but no associations were observed when participating cases were compared to non-participating controls (OR = 1.06, 95% CI: 0.71, 1.57) or to replacement controls (OR = 1.06, 95% CI: 0.71, 1.60). Conclusions: The observed risk estimates vary by type of control group, and no statistically significant association between wire codes and childhood leukemia is observed in the California population participating in the NCCLS. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Although selection bias in case-control studies has been studied extensively, little is known about selection of cases and controls among various ethnic groups. This study compares racial differences in childhood cancer rates as estimated by case-control studies with various design features. It also compares estimates of racial distribution among cases as reported by case-control studies to those observed for an ideal case series with complete ascertainment of cases for these studies or in population-based cancer registries in corresponding geographic regions and calendar periods. Methods: Peer-reviewed publications on childhood leukemia and brain tumors from North America, published between 1980 and 2007, were reviewed. Incidence data by race/ethnicity were compiled from research publications, federal cancer statistics, and cancer registries. Meta-analysis was conducted to assess racial/ethnic differences by study characteristics. Racial distributions of cases from published case-control studies were compared to those of a presumably noncensored case distribution (i.e. include both participating and non-participating cases in a case-control study) or cases recorded by cancer registries. Results: In interview-based case-control studies of childhood cancer, the proportion of Whites compared to non-Whites tended to be higher among controls than among cases; however, the opposite was true for record-based case-control studies. Additionally, the proportion of Whites tended to be higher among the participating cases in the published case-control studies compared to the proportion of Whites among the non-participating cases or in cancer registries. Conclusions: Investigators need to consider differential participation by racial group as a potential source of bias in the interpretation of case-control study results. [Copyright &y& Elsevier]

Background: The incidence of testicular germ cell tumors (TGCT) is increasing steadily in the United States, particularly among Latinos. TGCT is thought to be initiated in utero and exposure to endocrine-disrupting chemicals, suspected contributors to TGCT pathogenesis, during this critical developmental period may contribute to the rise.Objectives: To assess the relationship between fetal exposure to agricultural endocrine-disrupting pesticides (EDPs) and TGCT risk among adolescents in a diverse population in California.Methods: We conducted a registry-based case-control study of TGCT. Cases, diagnosed between 1997 and 2011, were 15-19 years of age (n = 381). Controls were matched on birth year and race/ethnicity (n = 762). Quantities (kilograms) of 33 pesticides applied within 3 km and 1 km radii of each individual's address before birth were estimated using the Pesticide Use Reporting database. Odds ratios (OR), 95% confidence intervals (CI), and population attributable risk (PAR) were calculated for each EDP (using log-2 transformed values). Risk models considered race/ethnicity, birth year, and neighborhood socioeconomic status.Results: A doubling of nearby acephate applications (3 km and 1 km radii) and malathion applications (1 km radius) was associated with increased risks of TGCT among Latinos only (OR = 1.09; 95% CI:1.01-1.17; 1.30; 95% CI:1.08-1.57, and 1.19; 95% CI:1.01-1.39, respectively), whereas application of carbaryl within a 3 km radius increased TGCT risk in non-Latinos only (OR = 1.14, 95% CI:1.01-1.28). We estimate that acephate was associated with approximately 10% of the TGCT PAR, malathion with 3% and carbaryl with 1%.Conclusions: TGCT among adolescents in California was associated with prenatal residential proximity to acephate and malathion among Latinos, and with carbaryl among non-Latinos. These results suggest that the rise in TGCT risk among Latinos may be associated with exposure to these pesticides. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the relationship between the risk of childhood leukemia and home remodeling, a surrogate for indoor chemical exposures.Methods: We collected information on remodeling activities carried out between birth and diagnosis in homes of 609 acute lymphoblastic leukemia (ALL) cases, 89 acute myeloid leukemia (AML) cases, and 893 matched controls participating in the California Childhood Leukemia Study (1995-2008). We used multivariable logistic regression to estimate the risk of ALL and AML associated with six remodeling activities: construction, painting, recarpeting, reflooring, roofing, and weatherproofing. Models were adjusted for age, sex, Hispanic ethnicity, race, household annual income, and residential mobility.Results: Construction in the home between birth and diagnosis was associated with a significant increase in ALL risk (odds ratio [OR]: 1.52, 95% confidence interval [CI]: 1.14-2.02) and a nonsignificant increase in AML risk (OR: 1.75, 95% CI: 0.98-3.15). No other remodeling activities were associated with ALL or AML risk in the main analysis. When stratifying by Hispanic ethnicity, a positive relationship between ALL risk and painting was evident in Hispanic children (OR: 1.47, 95% CI: 1.04-2.07).Conclusions: Specific home remodeling activities appeared to be associated with increased risk of childhood ALL. [ABSTRACT FROM AUTHOR]