Publications by authors named "Patricia A Buffler"

100 Publications

Association of genetic variation in IKZF1, ARID5B, and CEBPE and surrogates for early-life infections with the risk of acute lymphoblastic leukemia in Hispanic children.

Cancer Causes Control 2015 Apr 12;26(4):609-19. Epub 2015 Mar 12.

School of Public Health, University of California, Berkeley, Berkeley, CA, 94720, USA,

Background: Genome-wide association studies focusing on European-ancestry populations have identified ALL risk loci on IKZF1, ARID5B, and CEBPE. To capture the impacts of these genes on ALL risk in the California Hispanic population, we comprehensively assessed the variation within the genes and further assessed the joint effects between the genetic variation and surrogates for early-life infections (the presence of older siblings, daycare attendance, and ear infections).

Methods: Genotypic data for 323 Hispanic ALL cases and 454 controls from the California Childhood Leukemia Study were generated using Illumina OmniExpress v1 platform. Logistic regression assuming a log-additive model estimated odds ratios (OR) associated with each SNP, adjusted for age, sex, and the first five principal components. In addition, we examined potential interactions between six ALL risk alleles and surrogates for early-life infections using logistic regression models that included an interaction term.

Results: Significant associations between genotypes at IKZF1, ARID5B, and CEBPE and ALL risk were identified: rs7780012, OR 0.50, 95% confidence interval (CI) 0.35-0.71 (p = 0.004); rs7089424, OR 2.12, 95% CI 1.70-2.65 (p = 1.16 × 10(-9)); rs4982731, OR 1.69, 95% CI 1.37-2.08 (p = 2.35 × 10(-6)), respectively. Evidence for multiplicative interactions between genetic variants and surrogates for early-life infections with ALL risk was not observed.

Conclusions: Consistent with findings in non-Hispanic White population, our study showed that variants within IKZF1, ARID5B, and CEBPE were associated with increased ALL risk, and the effects for ARID5B and CEBPE were most prominent in the high-hyperdiploid ALL subtype in the California Hispanic population. Results implicate the ARID5B, CEBPE, and IKZF1 genes in the pathogenesis of childhood ALL.
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http://dx.doi.org/10.1007/s10552-015-0550-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504234PMC
April 2015

Residential levels of polybrominated diphenyl ethers and risk of childhood acute lymphoblastic leukemia in California.

Environ Health Perspect 2014 Oct 3;122(10):1110-6. Epub 2014 Jun 3.

Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA.

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.
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http://dx.doi.org/10.1289/ehp.1307602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4181922PMC
October 2014

Persistent organic pollutants in dust from older homes: learning from lead.

Am J Public Health 2014 Jul 15;104(7):1320-6. Epub 2014 May 15.

Todd P. Whitehead, Catherine Metayer, Robert B. Gunier, Stephen M. Rappaport, and Patricia A. Buffler are with the School of Public Health, University of California, Berkeley. Mary H. Ward, Joanne S. Colt, and Nicole C. Deziel are with the Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.

Objectives: We aimed to (1) evaluate the relation between home age and concentrations of multiple chemical contaminants in settled dust and (2) discuss the feasibility of using lead hazard controls to reduce children's exposure to persistent organic pollutants.

Methods: As part of the California Childhood Leukemia Study, from 2001 to 2007, we used a high-volume small surface sampler and household vacuum cleaners to collect dust samples from 583 homes and analyzed the samples for 94 chemicals with gas chromatography-mass spectrometry and inductively coupled plasma mass spectrometry. We evaluated relations between chemical concentrations in dust and home age with Spearman rank correlation coefficients.

Results: Dust concentrations of lead, polychlorinated biphenyls, organochlorine insecticides, and polycyclic aromatic hydrocarbons were correlated with home age (ρ > 0.2; P < .001), whereas concentrations of pyrethroid insecticides and polybrominated diphenyl ethers were not.

Conclusions: Dust in older homes contains higher levels of multiple, persistent chemicals than does dust in newer homes. Further development of strategies to reduce chemical exposures for children living in older homes is warranted.
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http://dx.doi.org/10.2105/AJPH.2013.301835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4056196PMC
July 2014

Genomic ancestry and somatic alterations correlate with age at diagnosis in Hispanic children with B-cell acute lymphoblastic leukemia.

Am J Hematol 2014 Jul 18;89(7):721-5. Epub 2014 Apr 18.

Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, 94143; Program in Cancer Genetics, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, 94143.

Hispanic children have a higher incidence of acute lymphoblastic leukemia (ALL) than non-Hispanic whites but tend to be diagnosed at older ages. In genome-wide association studies, Native American ancestry and polymorphisms in six genes have been associated with ALL risk. In multivariable regression models, we investigated whether genomic ancestry, inherited risk SNPs, or acquired somatic alterations were associated with differences in age at diagnosis in Hispanic children with B-cell ALL. Genome-wide array data were used to estimate each participant's percent membership in the three Hispanic ancestral populations: Native American, African, and European. Each 20% increase in European ancestry was associated with a six month younger age at diagnosis (95% CI = 0.36-11.6 months, P = 0.037). Correspondingly, each 20% increase in Native American ancestry was associated with a six-month older age at diagnosis (P = 0.037). Both the TEL-AML1 translocation and high-hyperdiploidy were associated with younger age at diagnosis (24.4 months, P = 2.0 x 10(-4) and 12.4 months, P = 0.011, respectively), while CDKN2A and IKZF1 deletions were associated with older age at diagnosis (19.7 months, P = 7.0 x 10(-4) and 18.1 months, P = 0.012, respectively). No associations with age at diagnosis were observed for RAS mutation, PAX5 deletion or for known heritable risk alleles in IKZF1, CDKN2A, PIP4K2A, GATA3, ARID5B, or CEBPE. Because younger age at diagnosis is associated with improved treatment outcomes for children with ALL, the effect of European ancestry on ALL survival may be mediated by its effect on age at diagnosis, or by proxy, its association with more treatable molecular subtypes of ALL.
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http://dx.doi.org/10.1002/ajh.23727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4069235PMC
July 2014

Potential role of selection bias in the association between childhood leukemia and residential magnetic fields exposure: a population-based assessment.

Cancer Epidemiol 2014 Jun 26;38(3):307-13. Epub 2014 Mar 26.

School of Public Health, University of California, Berkeley, CA, United States.

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.
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http://dx.doi.org/10.1016/j.canep.2014.02.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4140526PMC
June 2014

Mode of delivery and risk of childhood leukemia.

Cancer Epidemiol Biomarkers Prev 2014 May 11;23(5):876-81. Epub 2014 Mar 11.

Authors' Affiliations: Departments of Epidemiology; and Biostatistics, University of California, Berkeley; Department of Epidemiology and Biostatistics, University of California, San Francisco; Department of Pediatric Oncology, Children's Hospital Central California, Madera; and Division of Pediatric Hematology/Oncology, UCLA David Geffen School of Medicine, Los Angeles, California.

Background: Childhood infection and immune response have long been suspected in the etiology of childhood leukemia, specifically acute lymphoblastic leukemia (ALL). Normal primary inoculation of the core human microbiome is circumvented by cesarean section (CS) delivery, which is a proposed modulator of both immune response and early-life infection.

Methods: In this study, we examined CS delivery and the risk of childhood leukemia using data from the California Childhood Leukemia Study (CCLS) case-control study and additive logistic regression models.

Results: We observed no association between CS and acute myelogenous leukemia [OR, 0.96; 95% confidence interval (CI), 0.52-1.55]. We observed a suggestive association for ALL and CS (OR, 1.22; 95% CI, 0.97-1.54). When examining common ALL (cALL), defined as ALL with expression of CD10 and CD19 surface antigens and diagnosis occurring between 2 and 5.9 years of age, we found a significant association with CS (OR, 1.44; 95% CI, 1.0-2.06). ALL subjects that are not cALL showed a similar risk as ALL overall (OR, 1.15; 95% CI, 0.91-1.44). Because of previous findings suggesting effect modification, we stratified cALL subjects by Hispanic status. Although we observed no relationship for CS in non-Hispanics (OR, 1.14; 95% CI, 0.72-1.79), we did observe a strong association between cALL and CS in Hispanics (OR, 2.34; 95% CI, 1.23-4.46).

Conclusion: Within the CCLS, CS delivery seems to be associated with cALL and Hispanic subjects may be driving the association.

Impact: Further research combined with investigations into response to early infection and the microbiome is warranted.
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http://dx.doi.org/10.1158/1055-9965.EPI-13-1098DOI Listing
May 2014

Highly-cited estimates of the cumulative incidence and recurrence of vulvovaginal candidiasis are inadequately documented.

BMC Womens Health 2014 Mar 10;14(1):43. Epub 2014 Mar 10.

Division of Epidemiology, University of California, Berkeley, USA.

Background: Available literature concerning the epidemiologic or clinical features of vulvovaginal candidiasis commonly reports that: 75% of women will experience an episode of vulvovaginal candidiasis in their lifetimes, 50% of whom will experience at least a second episode, and 5-10% of all women will experience recurrent vulvovaginal candidiasis (≥4 episodes/1 year). In this debate we traced the three commonly cited statistics to their presumed origins.

Discussion: It is apparent that these figures were inadequately documented and lacked supporting epidemiologic evidence. Population-based studies are needed to make reliable estimates of the lifetime risk of vulvovaginal candidiasis and the proportion of women who experience recurrent candidiasis.

Summary: The extent to which vulvovaginal candidiasis is a source of population-level morbidity remains uncertain.
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http://dx.doi.org/10.1186/1472-6874-14-43DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3975582PMC
March 2014

Making prospective registration of observational research a reality.

Sci Transl Med 2014 Feb;6(224):224cm1

Clinical Research Program, Pasqual Maragall Foundation, E-08003 Barcelona, Spain.

The vast majority of health-related observational studies are not prospectively registered and the advantages of registration have not been fully appreciated. Nonetheless, international standards require approval of study protocols by an independent ethics committee before the study can begin. We suggest that there is an ethical and scientific imperative to publicly preregister key information from newly approved protocols, which should be required by funders. Ultimately, more complete information may be publicly available by disclosing protocols, analysis plans, data sets, and raw data.
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http://dx.doi.org/10.1126/scitranslmed.3007513DOI Listing
February 2014

The role of KIR genes and their cognate HLA class I ligands in childhood acute lymphoblastic leukemia.

Blood 2014 Apr 11;123(16):2497-503. Epub 2014 Feb 11.

Department of Epidemiology and Biostatistics and.

Killer cell immunoglobulin-like receptors (KIRs), via interaction with their cognate HLA class I ligands, play a crucial role in the development and activity of natural killer cells. Following recent reports of KIR gene associations in childhood acute lymphoblastic leukemia (ALL), we present a more in-depth investigation of KIR genes and their cognate HLA ligands on childhood ALL risk. Genotyping of 16 KIR genes, along with HLA class I groups C1/C2 and Bw4 supertype ligands, was carried out in 212 childhood ALL cases and 231 healthy controls. Frequencies of KIR genes, KIR haplotypes, and combinations of KIR-HLA ligands were tested for disease association using logistic regression analyses. KIR A/A genotype frequency was significantly increased in cases (33.5%) compared with controls (24.2%) (odds ratio [OR] = 1.57; 95% confidence interval [CI], 1.04-2.39). Stratifying analysis by ethnicity, a significant difference in KIR genotype frequency was demonstrated in Hispanic cases (34.2%) compared with controls (21.9%) (OR = 1.86; 95% CI, 1.05-3.31). Homozygosity for the HLA-Bw4 allele was strongly associated with increased ALL risk exclusively in non-Hispanic white children (OR = 3.93; 95% CI, 1.44-12.64). Our findings suggest a role for KIR genes and their HLA ligands in childhood ALL etiology that may vary among ethnic groups.
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http://dx.doi.org/10.1182/blood-2013-11-540625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3990912PMC
April 2014

Polychlorinated biphenyls in residential dust: sources of variability.

Environ Sci Technol 2014 16;48(1):157-64. Epub 2013 Dec 16.

University of California, Berkeley, School of Public Health, 50 University Hall MC 7360, Berkeley, California 94720, United States.

We characterized the variability in concentrations of polychlorinated biphenyls (PCBs) measured in residential dust. Vacuum cleaner samples were collected from 289 homes in the California Childhood Leukemia Study during two sampling rounds from 2001 to 2010 and 15 PCBs were measured by high resolution gas chromatography-mass spectrometry. Median concentrations of the most abundant PCBs (i.e., PCBs 28, 52, 101, 105, 118, 138, 153, and 180) ranged from 1.0-5.8 ng per g of dust in the first sampling round and from 0.8-3.4 ng/g in the second sampling round. For each of these eight PCBs, we used a random-effects model to apportion total variation into regional variability (6-11%), intraregional between-home variability (27-56%), within-home variability over time (18-52%), and within-sample variability (9-16%). In mixed-effects models, differences in PCB concentrations between homes were explained by home age, with older homes having higher PCB levels. Differences in PCB concentrations within homes were explained by decreasing time trends. Estimated half-lives ranged from 5-18 years, indicating that PCBs are removed very slowly from the indoor environment. Our findings suggest that it may be feasible to use residential dust for retrospective assessment of PCB exposures in studies of children's health.
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http://dx.doi.org/10.1021/es403863mDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3941978PMC
June 2015

GATA3 risk alleles are associated with ancestral components in Hispanic children with ALL.

Blood 2013 Nov;122(19):3385-7

Division of Neuroepidemiology, Department of Neurological Surgery and Program in Cancer Genetics, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.

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http://dx.doi.org/10.1182/blood-2013-08-524124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3821727PMC
November 2013

SNP association mapping across the extended major histocompatibility complex and risk of B-cell precursor acute lymphoblastic leukemia in children.

PLoS One 2013 22;8(8):e72557. Epub 2013 Aug 22.

School of Public Health, University of California, Berkeley, Berkeley, California, USA.

The extended major histocompatibility complex (xMHC) is the most gene-dense region of the genome and harbors a disproportionately large number of genes involved in immune function. The postulated role of infection in the causation of childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) suggests that the xMHC may make an important contribution to the risk of this disease. We conducted association mapping across an approximately 4 megabase region of the xMHC using a validated panel of single nucleotide polymorphisms (SNPs) in childhood BCP-ALL cases (n=567) enrolled in the Northern California Childhood Leukemia Study (NCCLS) compared with population controls (n=892). Logistic regression analyses of 1,145 SNPs, adjusted for age, sex, and Hispanic ethnicity indicated potential associations between several SNPs and childhood BCP-ALL. After accounting for multiple comparisons, one of these included a statistically significant increased risk associated with rs9296068 (OR=1.40, 95% CI=1.19-1.66, corrected p=0.036), located in proximity to HLA-DOA. Sliding window haplotype analysis identified an additional locus located in the extended class I region in proximity to TRIM27 tagged by a haplotype comprising rs1237485, rs3118361, and rs2032502 (corrected global p=0.046). Our findings suggest that susceptibility to childhood BCP-ALL is influenced by genetic variation within the xMHC and indicate at least two important regions for future evaluation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0072557PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3749982PMC
June 2014

Socioeconomic status and lung cancer: unraveling the contribution of genetic admixture.

Am J Public Health 2013 Oct 15;103(10):e73-80. Epub 2013 Aug 15.

At the time of the study, Melinda C. Aldrich was with the Division of Epidemiology, School of Public Health, University of California, Berkeley. Steve Selvin is with the Division of Biostatistics, School of Public Health, University of California, Berkeley. Margaret R. Wrensch, Helen M. Hansen, and John K. Wiencke are with the Department of Neurologic Surgery, University of California, San Francisco. Jennette D. Sison was with the Department of Neurologic Surgery, University of California, San Francisco. Charles P. Quesenberry Jr, is with the Division of Research, Kaiser Permanente, Oakland, CA. Michael F. Seldin is with the Departments of Biological Chemistry and Medicine, University of California, Davis. Lisa F. Barcellos and Patricia A. Buffler are with the Division of Epidemiology, School of Public Health, University of California, Berkeley.

Objectives: We examined the relationship between genetic ancestry, socioeconomic status (SES), and lung cancer among African Americans and Latinos.

Methods: We evaluated SES and genetic ancestry in a Northern California lung cancer case-control study (1998-2003) of African Americans and Latinos. Lung cancer case and control participants were frequency matched on age, gender, and race/ethnicity. We assessed case-control differences in individual admixture proportions using the 2-sample t test and analysis of covariance. Logistic regression models examined associations among genetic ancestry, socioeconomic characteristics, and lung cancer.

Results: Decreased Amerindian ancestry was associated with higher education among Latino control participants and greater African ancestry was associated with decreased education among African lung cancer case participants. Education was associated with lung cancer among both Latinos and African Americans, independent of smoking, ancestry, age, and gender. Genetic ancestry was not associated with lung cancer among African Americans.

Conclusions: Findings suggest that socioeconomic factors may have a greater impact than genetic ancestry on lung cancer among African Americans. The genetic heterogeneity and recent dynamic migration and acculturation of Latinos complicate recruitment; thus, epidemiological analyses and findings should be interpreted cautiously.
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http://dx.doi.org/10.2105/AJPH.2013.301370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3780736PMC
October 2013

Levels of nicotine in dust from homes of smokeless tobacco users.

Nicotine Tob Res 2013 Dec 24;15(12):2045-52. Epub 2013 Jul 24.

School of Public Health, University of California, Berkeley, CA;

Background: Smokeless tobacco products, such as chewing tobacco or moist snuff, contain many of the same constituents as tobacco smoke and are also known to cause cancer; however, little attention has been paid to indirect exposure of children to tobacco constituents via parental smokeless tobacco use.

Methods: As part of the California Childhood Leukemia Study, we collected dust samples from 6 residences occupied by smokeless tobacco users, 6 residences occupied by active smokers, and 20 tobacco-free residences. Children's potential for exposure to tobacco constituents was assessed using nicotine concentrations in vacuum dust measured by gas chromatography-mass spectrometry.

Results: Median nicotine concentrations for residences with smokeless tobacco users were significantly greater than median nicotine concentrations for tobacco-free homes and similar to median nicotine concentrations in homes of active smokers. Using generalized estimating equations derived from a multivariable marginal model to adjust for a history of parental smoking, income, residence construction date, and mother's age and race/ethnicity, we found nicotine levels from homes of smokeless tobacco users to be 21-fold higher than nicotine levels from tobacco-free homes. Based on mass balance equations, we hypothesize that nicotine is transferred to floors in homes of smokeless tobacco users primarily as a constituent of tobacco that is spilled or expectorated.

Conclusions: Based on our findings, we conclude that children living with smokeless tobacco users may be exposed to nicotine and other constituents of tobacco via contact with contaminated dust and household surfaces.
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http://dx.doi.org/10.1093/ntr/ntt096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3819978PMC
December 2013

Tobacco smoke exposure and the risk of childhood acute lymphoblastic and myeloid leukemias by cytogenetic subtype.

Cancer Epidemiol Biomarkers Prev 2013 Sep 12;22(9):1600-11. Epub 2013 Jul 12.

School of Public Health, University of California, 1995 University Avenue, Suite 460, Berkeley, CA94704-7392, USA.

Background: Tobacco smoke contains carcinogens known to damage somatic and germ cells. We investigated the effect of tobacco smoke on the risk of childhood acute lymphoblastic leukemia (ALL) and myeloid leukemia (AML), especially subtypes of prenatal origin such as ALL with translocation t(12;21) or high-hyperdiploidy (51-67 chromosomes).

Methods: We collected information on exposures to tobacco smoking before conception, during pregnancy, and after birth in 767 ALL cases, 135 AML cases, and 1,139 controls (1996-2008). Among cases, chromosome translocations, deletions, or aneuploidy were identified by conventional karyotype and fluorescence in situ hybridization.

Results: Multivariable regression analyses for ALL and AML overall showed no definite evidence of associations with self-reported (yes/no) parental prenatal active smoking and child's passive smoking. However, children with history of paternal prenatal smoking combined with postnatal passive smoking had a 1.5-fold increased risk of ALL [95% confidence interval (CI), 1.01-2.23], compared to those without smoking history (ORs for pre- or postnatal smoking only were close to one). This joint effect was seen for B-cell precursor ALL with t(12;21) (OR = 2.08; 95% CI, 1.04-4.16), but not high hyperdiploid B-cell ALL. Similarly, child's passive smoking was associated with an elevated risk of AML with chromosome structural changes (OR = 2.76; 95% CI, 1.01-7.58), but not aneuploidy.

Conclusions: Our data suggest that exposure to tobacco smoking was associated with increased risks of childhood ALL and AML; and risks varied by timing of exposure (before and/or after birth) and cytogenetic subtype, based on imprecise estimates.

Impact: Parents should limit exposures to tobacco smoke before and after the child's birth.
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http://dx.doi.org/10.1158/1055-9965.EPI-13-0350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3769478PMC
September 2013

Genetic variants in ARID5B and CEBPE are childhood ALL susceptibility loci in Hispanics.

Cancer Causes Control 2013 Oct 9;24(10):1789-95. Epub 2013 Jul 9.

Division of Epidemiology, School of Public Health, University of California, 1995 University Ave, Ste 460, Berkeley, CA, 94704, USA,

Recent genome-wide studies conducted in European Whites have identified novel susceptibility genes for childhood acute lymphoblastic leukemia (ALL). We sought to examine whether these loci are susceptibility genes among Hispanics, whose reported incidence of childhood ALL is the highest of all ethnic groups in California, and whether their effects differ between Hispanics and non-Hispanic Whites (NHWs). We genotyped 13 variants in these genes among 706 Hispanic (300 cases, 406 controls) and 594 NHW (225 cases, 369 controls) participants in a matched population-based case-control study in California. We found significant associations for the five studied ARID5B variants in both Hispanics (p values of 1.0 × 10(-9) to 0.004) and NHWs (p values of 2.2 × 10(-6) to 0.018). Risk estimates were in the same direction in both groups (ORs of 1.53-1.99 and 1.37-1.84, respectively) and strengthened when restricted to B-cell precursor high-hyperdiploid ALL (>50 chromosomes; ORs of 2.21-3.22 and 1.67-2.71, respectively). Similar results were observed for the single CEBPE variant. Hispanics and NHWs exhibited different susceptibility loci at CDKN2A. Although IKZF1 loci showed significant susceptibility effects among NHWs (p < 1 × 10(-5)), their effects among Hispanics were in the same direction but nonsignificant, despite similar minor allele frequencies. Future studies should examine whether the observed effects vary by environmental, immunological, or lifestyle factors.
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http://dx.doi.org/10.1007/s10552-013-0256-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3771434PMC
October 2013

Fetal growth and childhood acute lymphoblastic leukemia: findings from the childhood leukemia international consortium.

Int J Cancer 2013 Dec 1;133(12):2968-79. Epub 2013 Aug 1.

Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, WA, Australia, On behalf of the Aus-ALL Consortium (Australia).

Positive associations have been reported between the measures of accelerated fetal growth and risk of childhood acute lymphoblastic leukemia (ALL). We investigated this association by pooling individual-level data from 12 case-control studies participating in the Childhood Leukemia International Consortium. Two measures of fetal growth-weight-for-gestational-age and proportion of optimal birth weight (POBW)-were analysed. Study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression, and combined in fixed effects meta-analyses. Pooled analyses of all data were also undertaken using multivariable logistic regression. Subgroup analyses were undertaken when possible. Data on weight for gestational age were available for 7,348 cases and 12,489 controls from all 12 studies and POBW data were available for 1,680 cases and 3,139 controls from three studies. The summary ORs from the meta-analyses were 1.24 (95% CI: 1.13, 1.36) for children who were large for gestational age relative to appropriate for gestational age, and 1.16 (95% CI: 1.09, 1.24) for a one-standard deviation increase in POBW. The pooled analyses produced similar results. The summary and pooled ORs for small-for-gestational-age children were 0.83 (95% CI: 0.75, 0.92) and 0.86 (95% CI: 0.77, 0.95), respectively. Results were consistent across subgroups defined by sex, ethnicity and immunophenotype, and when the analysis was restricted to children who did not have high birth weight. The evidence that accelerated fetal growth is associated with a modest increased risk of childhood ALL is strong and consistent with known biological mechanisms involving insulin-like growth factors. © 2013 UICC.
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http://dx.doi.org/10.1002/ijc.28314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3797193PMC
December 2013

Polybrominated diphenyl ethers in residential dust: sources of variability.

Environ Int 2013 Jul 27;57-58:11-24. Epub 2013 Apr 27.

University of California, Berkeley, School of Public Health, 50 University Hall, MC 7360, Berkeley, CA 94720, USA.

We characterized the sources of variability for polybrominated diphenyl ethers (PBDEs) in residential dust and provided guidance for investigators who plan to use residential dust to assess exposure to PBDEs. We collected repeat dust samples from 292 households in the Northern California Childhood Leukemia Study during two sampling rounds (from 2001 to 2007 and during 2010) using household vacuum cleaners and measured 22 PBDEs using high resolution gas chromatography-high resolution mass spectrometry. Median concentrations for individual PBDEs ranged from <0.1-2500ng per g of dust. For each of eight representative PBDEs, we used a random-effects model to apportion total variance into regional variability (0-11%), intra-regional between-household variability (17-50%), within-household variability over time (38-74%), and within-sample variability (0-23%) and we used a mixed-effects model to identify determinants of PBDE levels. Regional differences in PBDE dust levels were associated with residential characteristics that differed by region, including the presence of furniture with exposed or crumbling foam and the recent installation of carpets in the residence. Intra-regional differences between households were associated with neighborhood urban density, racial and ethnic characteristics, and to a lesser extent, income. For some PBDEs, 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. Our findings indicate that it may be feasible to use residential dust for retrospective assessment of PBDE exposures in studies of children's health (e.g., the Northern California Childhood Leukemia Study).
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http://dx.doi.org/10.1016/j.envint.2013.03.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3668857PMC
July 2013

Blood levels of folate at birth and risk of childhood leukemia.

Cancer Epidemiol Biomarkers Prev 2013 Jun 10;22(6):1088-94. Epub 2013 Apr 10.

UC Berkeley School of Public Health, 1995 University Ave, Ste 460, Berkeley CA 94704, USA.

Background: A role for folate in cancer etiology has long been suspected because of folate's function as a cofactor in DNA methylation and maintenance of DNA synthesis. Previous case-control studies examining the association between risk of childhood acute lymphoblastic leukemia (ALL) and mothers' self-reported folate intake and supplementation have been inconclusive.

Materials And Methods: We used a quantitative microbiologic assay to measure newborn folate concentrations in archived dried bloodspots collected at birth from 313 incident ALL cases, 44 incident acute myeloid leukemia (AML) cases, and 405 matched population-based controls.

Results: Overall, we found no difference in hemoglobin-normalized newborn folate concentrations (HbFol, nmol/g) between ALL cases and controls (2.76 vs. 2.77, P = 0.97) or between AML cases and controls (2.93 vs. 2.76, P = 0.32). Null results persisted after stratification by both birth period (1982-94, 1995-98, and 1999-2002) to account for the start of folate fortification of grain products in the United States, and by self-reported maternal prepregnancy supplement use. Similarly, no association was observed for major ALL subgroups.

Conclusions: Our results do not support an association between birth folate concentrations and risk of childhood AML or major ALL subgroups.

Impact: However, they do not rule out a role for folate through exposures after birth or in early stages of fetal development.
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http://dx.doi.org/10.1158/1055-9965.EPI-12-1438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3681890PMC
June 2013

Current perspective on the global and United States cancer burden attributable to lifestyle and environmental risk factors.

Annu Rev Public Health 2013 ;34:97-117

School of Public Health, Department of Epidemiology, University of Michigan, Ann Arbor, Michigan 48109, USA.

Our objective is to provide a current perspective on the avoidable causes of global and US cancer incidence and mortality. Cancer registry-based incidence patterns, population behavioral risk-factor survey data, and systematic reviews of epidemiologic studies are the basis for estimates of relative risk, the prevalence of exposures to various lifestyle and environmental risk factors, and their impact expressed as population attributable fractions (PAFs). Of the total 59 million global deaths in 2008, 12-13% were attributed to cancer. The increasing burden of cancers in low- and middle-income countries (LMICs) is attributable in part to increasing urbanization, expansion of the adult population at risk, and increasing or persistent exposures to infectious agents, tobacco, and dietary deficiencies. Attributable fractions for lifestyle and environmental risk factors are summarized for the United States, the United Kingdom, and France. Assuming minimal overlap in the distribution of risk factors in the population and discounting the potential for interaction in their combined effects, we estimate that a maximum of 60% of cancer deaths in the United States may be attributed to eight risk factors: tobacco, alcohol, ionizing and solar radiations, occupations, infectious agents, obesity, and physical inactivity.
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http://dx.doi.org/10.1146/annurev-publhealth-031912-114350DOI Listing
September 2013

Polycyclic aromatic hydrocarbons in residential dust: sources of variability.

Environ Health Perspect 2013 May 5;121(5):543-50. Epub 2013 Mar 5.

School of Public Health, University of California, Berkeley, Berkeley, California, USA.

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.
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http://dx.doi.org/10.1289/ehp.1205821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3672903PMC
May 2013

Determinants of polychlorinated biphenyls in dust from homes in California, USA.

Environ Sci Process Impacts 2013 Feb 26;15(2):339-46. Epub 2012 Nov 26.

School of Public Health, University of California, Berkeley, CA, USA.

Polychlorinated biphenyl (PCB) production ceased in the U.S. over 30 years ago, but these persistent chemicals remain ubiquitous contaminants. Here, we evaluate potential determinants of PCB levels in dust from California homes including characteristics of the residence as well as the residents' habits and occupations. Dust was collected from 415 households as part of a large case-control study (the Northern California Childhood Leukaemia Study), using a high-volume small surface sampler. Dust concentrations of 6 PCBs (PCB-105, PCB-118, PCB-138, PCB-153, PCB-170, and PCB-180) were measured using gas chromatography-mass spectrometry. Individual PCB detection rates ranged from 9% to 54% with PCB concentrations ranging from below detection (1 or 2 ng g (-1)) to 270 ng g(-1) and PCB loadings ranging from below detection to 960 ng m (-2). Multivariable linear and logistic regression models were used to identify potential determinants of residential PCB contamination based on in-home interviews and residential geographic locations. We observed that residences built prior to 1980 had higher odds of PCB detection and higher PCB loadings than more recently constructed homes. Households where residents typically did not remove their shoes had higher PCB dust loadings than households where residents did. PCBs were less likely to be detected in carpet dust from households that had frequently vacuumed or replaced carpets compared to other households. Since we used a cross-sectional dust sampling protocol and report significant, but modest, effects of these determinants on levels of PCBs in residential dust, our results should be interpreted with caution. Longitudinal studies to determine optimal strategies for reducing PCBs in homes are warranted.
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http://dx.doi.org/10.1039/c2em30721aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4439093PMC
February 2013

The Childhood Leukemia International Consortium.

Cancer Epidemiol 2013 Jun 9;37(3):336-47. Epub 2013 Feb 9.

University of California, Berkeley, School of Public Health, 1995 University Avenue, Suite 460, Berkeley, CA 94704-1070, USA.

Background: Acute leukemia is the most common cancer in children under 15 years of age; 80% are acute lymphoblastic leukemia (ALL) and 17% are acute myeloid leukemia (AML). Childhood leukemia shows further diversity based on cytogenetic and molecular characteristics, which may relate to distinct etiologies. Case-control studies conducted worldwide, particularly of ALL, have collected a wealth of data on potential risk factors and in some studies, biospecimens. There is growing evidence for the role of infectious/immunologic factors, fetal growth, and several environmental factors in the etiology of childhood ALL. The risk of childhood leukemia, like other complex diseases, is likely to be influenced both by independent and interactive effects of genes and environmental exposures. While some studies have analyzed the role of genetic variants, few have been sufficiently powered to investigate gene-environment interactions.

Objectives: The Childhood Leukemia International Consortium (CLIC) was established in 2007 to promote investigations of rarer exposures, gene-environment interactions and subtype-specific associations through the pooling of data from independent studies.

Methods: By September 2012, CLIC included 22 studies (recruitment period: 1962-present) from 12 countries, totaling approximately 31000 cases and 50000 controls. Of these, 19 case-control studies have collected detailed epidemiologic data, and DNA samples have been collected from children and child-parent trios in 15 and 13 of these studies, respectively. Two registry-based studies and one study comprising hospital records routinely obtained at birth and/or diagnosis have limited interview data or biospecimens.

Conclusions: CLIC provides a unique opportunity to fill gaps in knowledge about the role of environmental and genetic risk factors, critical windows of exposure, the effects of gene-environment interactions and associations among specific leukemia subtypes in different ethnic groups.
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http://dx.doi.org/10.1016/j.canep.2012.12.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3652629PMC
June 2013

Exposure to herbicides in house dust and risk of childhood acute lymphoblastic leukemia.

J Expo Sci Environ Epidemiol 2013 Jul 16;23(4):363-70. Epub 2013 Jan 16.

School of Public Health, University of California, Berkeley, California, USA.

We examine the association between exposure to herbicides and childhood acute lymphoblastic leukemia (ALL). Dust samples were collected from homes of 269 ALL cases and 333 healthy controls (<8 years of age at diagnosis/reference date and residing in same home since diagnosis/reference date) in California, using a high-volume surface sampler or household vacuum bags. Amounts of agricultural or professional herbicides (alachlor, metolachlor, bromoxynil, bromoxynil octanoate, pebulate, butylate, prometryn, simazine, ethalfluralin, and pendimethalin) and residential herbicides (cyanazine, trifluralin, 2-methyl-4-chlorophenoxyacetic acid (MCPA), mecoprop, 2,4-dichlorophenoxyacetic acid (2,4-D), chlorthal, and dicamba) were measured. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression. Models included the herbicide of interest, age, sex, race/ethnicity, household income, year and season of dust sampling, neighborhood type, and residence type. The risk of childhood ALL was associated with dust levels of chlorthal; compared to homes with no detections, ORs for the first, second, and third tertiles were 1.49 (95% CI: 0.82-2.72), 1.49 (95% CI: 0.83-2.67), and 1.57 (95% CI: 0.90-2.73), respectively (P-value for linear trend=0.05). The magnitude of this association appeared to be higher in the presence of alachlor. No other herbicides were identified as risk factors of childhood ALL. The data suggest that home dust levels of chlorthal, and possibly alachlor, are associated with increased risks of childhood ALL.
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http://dx.doi.org/10.1038/jes.2012.115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440472PMC
July 2013

Characterization of residential pesticide use and chemical formulations through self-report and household inventory: the Northern California Childhood Leukemia study.

Environ Health Perspect 2013 Feb 24;121(2):276-82. Epub 2012 Oct 24.

School of Public Health, University of California at Berkeley, Berkeley, California, USA.

Background: Home and garden pesticide use has been linked to cancer and other health outcomes in numerous epidemiological studies. Exposure has generally been self-reported, so the assessment is potentially limited by recall bias and lack of information on specific chemicals.

Objectives: As part of an integrated assessment of residential pesticide exposure, we identified active ingredients and described patterns of storage and use.

Methods: During a home interview of 500 residentially stable households enrolled in the Northern California Childhood Leukemia Study during 2001-2006, trained interviewers inventoried residential pesticide products and queried participants about their storage and use. U.S. Environmental Protection Agency registration numbers, recorded from pesticide product labels, and pesticide chemical codes were matched to public databases to obtain information on active ingredients and chemical class. Poisson regression was used to identify independent predictors of pesticide storage. Analyses were restricted to 259 participating control households.

Results: Ninety-five percent (246 of 259) of the control households stored at least one pesticide product (median, 4). Indicators of higher sociodemographic status predicted more products in storage. We identified the most common characteristics: storage areas (garage, 40%; kitchen, 20%), pests treated (ants, 33%; weeds, 20%), pesticide types (insecticides, 46%; herbicides, 24%), chemical classes (pyrethroids, 77%; botanicals, 50%), active ingredients (pyrethrins, 43%) and synergists (piperonyl butoxide, 42%). Products could contain multiple active ingredients.

Conclusions: Our data on specific active ingredients and patterns of storage and use will inform future etiologic analyses of residential pesticide exposures from self-reported data, particularly among households with young children.
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http://dx.doi.org/10.1289/ehp.1204926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3569677PMC
February 2013

HLA-DP genetic variation, proxies for early life immune modulation and childhood acute lymphoblastic leukemia risk.

Blood 2012 Oct 24;120(15):3039-47. Epub 2012 Aug 24.

School of Public Health, University of California, Berkeley, CA 94704, USA.

The human leukocyte antigen (HLA) genes are candidate genetic susceptibility loci for childhood acute lymphoblastic leukemia (ALL). We examined the effect of HLA-DP genetic variation on risk and evaluated its potential interaction with 4 proxies for early immune modulation, including measures of infectious exposures in infancy (presence of older siblings, daycare attendance, ear infections) and breastfeeding. A total of 585 ALL cases and 848 controls were genotyped at the HLA-DPA1 and DPB1 loci. Because of potential heterogeneity in effect by race/ethnicity, we included only non-Hispanic white (47%) and Hispanic (53%) children and considered these 2 groups separately in the analysis. Logistic regression analyses showed an increased risk of ALL associated with HLA-DPB1*01:01 (odds ratio [OR] = 1.43, 95% CI, 1.01-2.04) with no heterogeneity by Hispanic ethnicity (P = .969). Analyses of DPB1 supertypes showed a marked childhood ALL association with DP1, particularly for high-hyperdiploid ALL (OR = 1.83; 95% CI, 1.20-2.78). Evidence of interaction was found between DP1 and older sibling (P = .036), and between DP1 and breastfeeding (P = .094), with both showing statistically significant DP1 associations within the lower exposure categories only. These findings support an immune mechanism in the etiology of childhood ALL involving the HLA-DPB1 gene in the context of an insufficiently modulated immune system.
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http://dx.doi.org/10.1182/blood-2012-01-404723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471514PMC
October 2012

Fetal growth and body size genes and risk of childhood acute lymphoblastic leukemia.

Cancer Causes Control 2012 Sep 28;23(9):1577-85. Epub 2012 Jul 28.

School of Public Health, University of California Berkeley, Berkeley, CA, USA.

Accumulating evidence suggests that childhood acute lymphoblastic leukemia (ALL) may be initiated in utero or early in the postnatal period. High birth weight (or rapid fetal growth) is associated with risk of ALL, but the mechanisms are not understood. In a population-based epidemiologic study of childhood ALL, we utilized a haplotype-based approach to assess the role of eight genes involved in fetal growth and body size regulation in 377 childhood ALL cases and 448 controls. We found significant haplotype associations with risk of childhood ALL for IGF1 among non-Hispanics and Hispanics together (p = 0.002), for IGF2 among Hispanics (p = 0.040), and for IGF2R among Hispanics and non-Hispanics (p = 0.051 and 0.009, respectively). No haplotype associations were observed for IGF1R or the studied genes involved in body size regulation, including LEP, LEPR, GHRL, and NPY. Our study is the first to identify an association between the genes involved in the IGF axis and risk of childhood ALL. These findings for childhood ALL emphasize the importance of fetal growth, when lymphoid progenitor cells are not yet fully differentiated and therefore more susceptible to malignant transformation. Additional studies are needed to confirm these findings and identify specific causal variants.
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http://dx.doi.org/10.1007/s10552-012-0035-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3415610PMC
September 2012

Variation in xenobiotic transport and metabolism genes, household chemical exposures, and risk of childhood acute lymphoblastic leukemia.

Cancer Causes Control 2012 Aug 7;23(8):1367-75. Epub 2012 Jun 7.

Division of Epidemiology, UC Berkeley School of Public Health, University of California Berkeley, 1995 University Ave, , Berkeley, CA 94704, USA.

Background: Recent studies suggest that environmental exposures to pesticides, tobacco, and other xenobiotic chemicals may increase risk of childhood acute lymphoblastic leukemia (ALL). We sought to evaluate the role of genes involved in xenobiotic transport and metabolism in childhood ALL risk, both alone and in conjunction with household chemical exposures previously found to be associated with childhood ALL risk.

Methods: We conducted a population-based epidemiologic study of 377 cases and 448 controls in California, utilizing a haplotype-based approach to evaluate 42 xenobiotic transport and metabolism genes in conjunction with data on self-reported household chemical exposures.

Results: We identified significant associations of childhood ALL risk with haplotypes of ABCB1, ARNT, CYP2C8, CYP1A2, CYP1B1, and IDH1. In addition, certain haplotypes showed significant joint effects with self-reported household chemical exposures on risk of childhood ALL. Specifically, elevated risks associated with use of paints in the home (ever) and indoor insecticides (pre-birth) were limited to subjects carrying specific haplotypes of CYP2C8 and ABCB1, respectively.

Conclusions: Our results provide support for a role of xenobiotic transport and metabolism pathways in risk of childhood ALL and indicate that genes in these pathways may modulate the risk of disease associated with use of common household chemicals. Additional studies are needed to confirm these findings and localize specific causal variants.
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http://dx.doi.org/10.1007/s10552-012-9947-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3390694PMC
August 2012

Burden of disease, health indicators and challenges for epidemiology in North America.

Int J Epidemiol 2012 Apr 9;41(2):540-56. Epub 2012 Mar 9.

Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada.

Background: Commissioned by the International Epidemiological Association, this article is part of a series on burden of disease, health indicators and the challenges faced by epidemiologists in bringing their discoveries to provide equitable benefit to the populations in their regions and globally. This report covers the health status and epidemiological capacity in the North American region (USA and Canada).

Methods: We assessed data from country-specific sources to identify health priorities and areas of greatest need for modifiable risk factors. We examined inequalities in health as a function of social deprivation. We also reviewed information on epidemiological capacity building and scientific contributions by epidemiologists in the region.

Findings: The USA and Canada enjoy technologically advanced healthcare systems that, in principle, prioritize preventive services. Both countries experience a life expectancy at birth that is higher than the global mean. Health indicator measures are consistently worse in the USA than in Canada for many outcomes, although typically by only marginal amounts. Socio-economic and racial/ethnic disparities in indicators exist for many diseases and risk factors in the USA. To a lesser extent, these social inequalities also exist in Canada, particularly among the Aboriginal populations. Epidemiology is a well-established discipline in the region, with many degree-granting schools, societies and job opportunities in the public and private sectors. North American epidemiologists have made important contributions in disease control and prevention and provide nearly a third of the global scientific output via published papers.

Conclusions: Critical challenges for North American epidemiologists include social determinants of disease distribution and the underlying inequalities in access to and benefit from preventive services and healthcare, particularly in the USA. The gains in life expectancy also underscore the need for research on health promotion and prevention of disease and disability in older adults. The diversity in epidemiological subspecialties poses new challenges in training and accreditation and has occurred in parallel with a decrease in research funding.
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http://dx.doi.org/10.1093/ije/dys018DOI Listing
April 2012