Publications by authors named "Claire Infante-Rivard"

86 Publications

Reply to Sjölander and VanderWeele on 'Bias factor, maximum bias and the E-value'.

Int J Epidemiol 2021 Mar 24. Epub 2021 Mar 24.

Department of Epidemiology, Biostatistics and Occupational Health, Faculty of Medicine, McGill University, Montréal, QC, Canada.

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http://dx.doi.org/10.1093/ije/dyab056DOI Listing
March 2021

Bias factor, maximum bias and the E-value: insight and extended applications.

Int J Epidemiol 2020 10;49(5):1509-1516

Department of Epidemiology, Biostatistics and Occupational Health, Faculty of Medicine, McGill University, Montréal, Québec, Canada.

Background: Unmeasured confounding can bias the relationship between exposure and outcome. Sensitivity analyses generate bias-adjusted measures but these are not much used; this may change with the availability of the E-value (for evidence for causality in observational studies), appealing for its ease of calculation. However, as currently proposed, the E-value has some practical limitations that may reduce its use.

Methods: We first provide some insight into the relationship between two established measures for unmeasured confounding: 'the bias factor' and the maximum value this bias factor can take ('the B bias'). These measures are the statistical foundation for the E-value. We use them to develop new E-value formulas for situations when it is not currently applicable such as e.g. when, not unusually, a negative relation between unmeasured confounder and outcome and a positive one with exposure are postulated. We also provide E-values on the odds ratio scale because, currently, even when using the odds ratio as the study measure in the calculation of E-value, the result is to be interpreted as a relative risk, which is somewhat inconvenient.

Results: The additional formulas for the E-value measure make it applicable in all possible scenarios defined by the combined directions between unmeasured confounder and both the exposure and outcome. In addition, E-value measures can now be interpreted as odds ratios if the observed results are reported on the same scale.

Conclusions: The E-value is part of newer sensitivity analyses methods for unmeasured confounding. We provide insight into its structure, underscoring its advantages and limitations, and expand its applications.
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http://dx.doi.org/10.1093/ije/dyaa127DOI Listing
October 2020

Reflection on modern methods: selection bias-a review of recent developments.

Int J Epidemiol 2018 10;47(5):1714-1722

Research Centre, Centre Hospitalier Universitaire (CHU) Sainte-Justine, Montréal, QC, Canada.

Selection bias remains a more difficult bias to understand than confounding or measurement error. Past definitions have not always been illuminating and a simple method (such as the change-in-estimate method for confounding) has not been available to determine its presence and magnitude in the study sample. A better understanding of the nature of the bias has led to the definition of endogenous selection bias. It is the result of conditioning on a collider variable, itself caused by two other variables; the latter variables become spuriously associated. Conditioning on a variable in the analysis that is a collider or on an indicator of sample selection has the same effect. Note that selection bias is possible even in the absence of a collider, but in the presence of endogenous selection bias, the concern is whether it is possible to identify a causal effect in the sample. Conditions have been outlined to determine that. However, even if conditions are met to identify a causal effect in the study sample, its generalization to a defined target population is not a given.We discuss the concept of endogeneity and the sources of endogenous selection bias in observational studies. We then briefly address the terms generalizability, target population (or alternative formulations) and transportability. We outline the explicit conditions to identify causal effects in studies affected by selection bias: they involve exchangeability between exposed and unexposed and exchangeability between sampled and unsampled. We briefly describe methods to generalize estimated causal effects to the target population. The latter usually require data from the target population. Finally we discuss sensitivity analyses; some are limited to providing an indication of the presence and direction of the bias and others can provide corrected estimates with user-supplied selection bias parameters.
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http://dx.doi.org/10.1093/ije/dyy138DOI Listing
October 2018

Advanced parental age as risk factor for childhood acute lymphoblastic leukemia: results from studies of the Childhood Leukemia International Consortium.

Eur J Epidemiol 2018 Oct 14;33(10):965-976. Epub 2018 May 14.

Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.

Advanced parental age has been associated with adverse health effects in the offspring including childhood (0-14 years) acute lymphoblastic leukemia (ALL), as reported in our meta-analysis of published studies. We aimed to further explore the association using primary data from 16 studies participating in the Childhood Leukemia International Consortium. Data were contributed by 11 case-control (CC) studies (7919 cases and 12,942 controls recruited via interviews) and five nested case-control (NCC) studies (8801 cases and 29,690 controls identified through record linkage of population-based health registries) with variable enrollment periods (1968-2015). Five-year paternal and maternal age increments were introduced in two meta-analyses by study design using adjusted odds ratios (OR) derived from each study. Increased paternal age was associated with greater ALL risk in the offspring (OR 1.05, 95% CI 1.00-1.11; OR 1.04, 95% CI 1.01-1.07). A similar positive association with advanced maternal age was observed only in the NCC results (OR 0.99, 95% CI 0.91-1.07, heterogeneity I = 58%, p = 0.002; OR 1.05, 95% CI 1.01-1.08). The positive association between parental age and risk of ALL was most marked among children aged 1-5 years and remained unchanged following mutual adjustment for the collinear effect of the paternal and maternal age variables; analyses of the relatively small numbers of discordant paternal-maternal age pairs were not fully enlightening. Our results strengthen the evidence that advanced parental age is associated with increased childhood ALL risk; collinearity of maternal with paternal age complicates causal interpretation. Employing datasets with cytogenetic information may further elucidate involvement of each parental component and clarify underlying mechanisms.
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http://dx.doi.org/10.1007/s10654-018-0402-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6384148PMC
October 2018

Living on a farm, contact with farm animals and pets, and childhood acute lymphoblastic leukemia: pooled and meta-analyses from the Childhood Leukemia International Consortium.

Cancer Med 2018 06 16;7(6):2665-2681. Epub 2018 Apr 16.

INSERM U1153, Epidemiology and Biostatistics Sorbonne Paris Cité Center (CRESS), Epidemiology of Childhood and Adolescent Cancers Team (EPICEA), Paris-Descartes University, Villejuif, France.

The associations between childhood acute lymphoblastic leukemia (ALL) and several factors related to early stimulation of the immune system, that is, farm residence and regular contacts with farm animals (livestock, poultry) or pets in early childhood, were investigated using data from 13 case-control studies participating in the Childhood Leukemia International Consortium. The sample included 7847 ALL cases and 11,667 controls aged 1-14 years. In all studies, the data were obtained from case and control parents using standardized questionnaires. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by unconditional logistic regression adjusted for age, sex, study, maternal education, and maternal age. Contact with livestock in the first year of life was inversely associated with ALL (OR = 0.65, 95% CI: 0.50, 0.85). Inverse associations were also observed for contact with dogs (OR = 0.92, 95% CI: 0.86, 0.99) and cats (OR = 0.87, 95% CI: 0.80, 0.94) in the first year of life. There was no evidence of a significant association with farm residence in the first year of life. The findings of these large pooled and meta-analyses add additional evidence to the hypothesis that regular contact with animals in early childhood is inversely associated with childhood ALL occurrence which is consistent with Greaves' delayed infection hypothesis.
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http://dx.doi.org/10.1002/cam4.1466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6010788PMC
June 2018

Genetic Association Family-Based Studies and Preeclampsia.

Paediatr Perinat Epidemiol 2018 01 27;32(1):13-15. Epub 2017 Oct 27.

Department of Epidemiology, Biostatistics and Occupational Health, Faculty of Medicine, McGill University, Montréal, QC, Canada.

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http://dx.doi.org/10.1111/ppe.12418DOI Listing
January 2018

Analysis of case-parent trios for imprinting effect using a loglinear model with adjustment for sex-of-parent-specific transmission ratio distortion.

Hum Genet 2017 08 19;136(8):951-961. Epub 2017 Jun 19.

Department of Decision Sciences, HEC Montréal, Montreal, QC, H3T 2A7, Canada.

Transmission ratio distortion (TRD) is a phenomenon where parental transmission of disease allele to the child does not follow the Mendelian inheritance ratio. TRD occurs in a sex-of-parent-specific or non-sex-of-parent-specific manner. An offset computed from the transmission probability of the minor allele in control-trios can be added to the loglinear model to adjust for TRD. Adjusting the model removes the inflation in the genotype relative risk (RR) estimate and Type 1 error introduced by non-sex-of-parent-specific TRD. We now propose to further extend this model to estimate an imprinting parameter. Some evidence suggests that more than 1% of all mammalian genes are imprinted. In the presence of imprinting, for example, the offspring inheriting an over-transmitted disease allele from the parent with a higher expression level in a neighboring gene is over-represented in the sample. TRD mechanisms such as meiotic drive and gametic competition occur in a sex-of-parent-specific manner. Therefore, sex-of-parent-specific TRD (ST) leads to over-representation of maternal or paternal alleles in the affected child. As a result, ST may bias the imprinting effect when present in the sample. We propose a sex-of-parent-specific transmission offset in adjusting the loglinear model to account for ST. This extended model restores the correct RR estimates for child and imprinting effects, adjusts for inflation in Type 1 error, and improves performance on sensitivity and specificity compared to the original model without ST offset. We conclude that to correctly interpret the association signal of an imprinting effect, adjustment for ST is necessary to ensure valid conclusions.
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http://dx.doi.org/10.1007/s00439-017-1824-5DOI Listing
August 2017

Traumatic Brain Injury in the Workplace.

Can J Neurol Sci 2017 Sep 22;44(5):518-524. Epub 2017 May 22.

1Department of Neurosurgery,Biostatistics and Occupational Health,McGill University,Montreal,Canada.

Objectives: Work-related traumatic brain injuries (TBIs) are not well documented in the literature. Published studies mostly rely on worker databases that fail to provide clinically relevant information. Our objective is to describe the characteristics of hospitalized patients and their work-related TBI.

Methods: We used the Québec provincial trauma and TBI program databases to identify all patients with a diagnosis of work-related TBI admitted to the Montreal General Hospital, a level 1 trauma center, between 2000 and 2014. Data from their medical records were extracted using a predetermined information sheet. Simple descriptive statistics (means and percentages) were used to summarize the data.

Results: A total of 285 cases were analyzed. Workplace TBI patients were middle-aged (mean, 43.62 years), overwhelmingly male (male:female 18:1), mostly healthy, and had completed a high school level education. Most workers were from the construction industry; falling was the most common mechanism of injury. The majority of patients (76.8%) presented with a mild TBI; only a minority (14%) required neurosurgery. The most common finding on computed tomography was skull fracture. The median length of hospitalization was 7 days, after which most patients were discharged directly home. A total of 8.1% died of their injuries.

Conclusions: Our study found that most hospitalized victims of work-related TBI had mild injury; however, some required neurosurgical intervention and a non-negligible proportion died of their injury. Improving fall prevention, accurately document helmet use and increasing the safety practice in the construction industry may help decrease work-related TBI burden.
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http://dx.doi.org/10.1017/cjn.2017.43DOI Listing
September 2017

Parental alcohol consumption and risk of leukemia in the offspring: a systematic review and meta-analysis.

Eur J Cancer Prev 2017 09;26(5):433-441

aDepartment of Hygiene, Epidemiology and Medical Statistics bFirst Department of Obstetrics and Gynecology, School of Medicine, University of Athens cHaematology-Oncology Unit, First Department of Pediatrics, Athens University Medical School, 'Aghia Sophia' Children's Hospital dDepartment of Pediatric Hematology-Oncology, 'Pan. & Agl. Kyriakou' Children's Hospital eDepartment of Pediatric Haematology-Oncology, 'Aghia Sophia' Children's Hospital, Athens f2nd Department of Pediatrics, Aristotelion University of Thessaloniki, AHEPA General Hospital gDepartment of Pediatric Hematology and Oncology, Hippokration Hospital, Thessaloniki hDepartment of Pediatric Hematology-Oncology, University Hospital of Heraklion, Heraklion, Greece iProgram Medical Neurosciences, Charité-Medicine University, Berlin, Germany jCentral American Institute for Studies on Toxic Substances, National University, Heredia, Costa Rica kFaculty of Public Health, University of Sao Paulo, Sao Paulo, Brazil lDepartment of Epidemiology, Biostatistics, and Occupational Health, Faculty of Medicine, McGill University, Montre[Combining Acute Accent]al, Que[Combining Acute Accent]bec, Canada.

Parental alcohol consumption before and during pregnancy has been linked to adverse outcomes in the offspring including leukemogenesis. We, therefore, aimed to systematically assess and quantitatively synthesize published data on the association of paternal consumption during preconception and maternal consumption during pregnancy with leukemia risk in childhood (0-14 years). Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched PubMed (until February 2016) and the reference lists of the relevant studies. Observational studies examining the association between parental alcohol consumption and childhood leukemia were considered eligible. Data extracted from 39 case-control studies (over 16 000 leukemia cases and 30 000 controls) were pooled and summary-effect estimates were calculated. Subgroup analyses were carried out by main acute leukemia type [lymphoblastic or myeloid), cytogenetics/genetic polymorphisms, and specific alcohol beverages. We found a statistically significant dose-response association of any level of maternal alcohol consumption compared with nondrinking during pregnancy exclusively with acute myeloid leukemia (AML) [odds ratio (OR)moderate consumption: 1.64, 95% confidence intervals (CIs): 1.23-2.17 and ORhigh consumption: 2.36, 95% CI: 1.60-3.49]. In contrast, no association of paternal preconception consumption with any leukemia type was noted. In beverage-specific analyses, only a positive association of maternal wine drinking with childhood AML was found, which was more pronounced in analyses including only studies on infant leukemia (ORwine: 2.12, 95% CI: 1.16-3.90). The largest ever meta-analysis shows a sizeable, statistically significant dose-response association of maternal alcohol consumption during index pregnancy with AML risk. Future research exploring the role of genetic polymorphisms is anticipated to shed light on the underlying pathophysiology.
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http://dx.doi.org/10.1097/CEJ.0000000000000350DOI Listing
September 2017

Analysis of Case-Parent Trios Using a Loglinear Model with Adjustment for Transmission Ratio Distortion.

Front Genet 2016 31;7:155. Epub 2016 Aug 31.

Department of Epidemiology, Biostatistics and Occupational Health, McGill UniversityMontréal, QC, Canada; Department of Psychiatry, McGill UniversityMontréal, QC, Canada; Douglas Mental Health University InstituteMontréal, QC, Canada.

Transmission of the two parental alleles to offspring deviating from the Mendelian ratio is termed Transmission Ratio Distortion (TRD), occurs throughout gametic and embryonic development. TRD has been well-studied in animals, but remains largely unknown in humans. The Transmission Disequilibrium Test (TDT) was first proposed to test for association and linkage in case-trios (affected offspring and parents); adjusting for TRD using control-trios was recommended. However, the TDT does not provide risk parameter estimates for different genetic models. A loglinear model was later proposed to provide child and maternal relative risk (RR) estimates of disease, assuming Mendelian transmission. Results from our simulation study showed that case-trios RR estimates using this model are biased in the presence of TRD; power and Type 1 error are compromised. We propose an extended loglinear model adjusting for TRD. Under this extended model, RR estimates, power and Type 1 error are correctly restored. We applied this model to an intrauterine growth restriction dataset, and showed consistent results with a previous approach that adjusted for TRD using control-trios. Our findings suggested the need to adjust for TRD in avoiding spurious results. Documenting TRD in the population is therefore essential for the correct interpretation of genetic association studies.
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http://dx.doi.org/10.3389/fgene.2016.00155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5005337PMC
September 2016

Assessment of occupational risks to extremely low frequency magnetic fields: Validation of an empirical non-expert approach.

Prev Med Rep 2016 Dec 31;4:148-54. Epub 2016 May 31.

Research Center, Hôpital Ste-Justine, 3175 Chemin de la Côte-Sainte-Catherine, Montréal, QuébecH3T 1C4, Canada; Department of Epidemiology, Biostatistics, and Occupational Health, Faculty of Medicine, McGill University, Montréal, Québec, Canada.

The expert method of exposure assignment involves relying on chemists or hygienists to estimate occupational exposures using information collected on study subjects. Once the estimation method for a particular contaminant has been made available in the literature, it is not known whether a non-expert, briefly trained by an expert remaining available to answer ad hoc questions, can provide reliable exposure estimates. We explored this issue by comparing estimates of exposure to extremely low frequency magnetic fields (ELF-MF) obtained by an expert to those from a non-expert. Using a published exposure matrix, both the expert and non-expert independently calculated a weekly time-weighted average exposure for 208 maternal jobs by considering three main determinants: the work environment, magnetic field sources, and duration of use or exposure to given sources. Agreement between assessors was tested using the Bland-Altman 95% limits of agreement. The overall mean difference in estimates between the expert and non-expert was 0.004 μT (standard deviation 0.104). The 95% limits of agreement were - 0.20 μT and + 0.21 μT. The work environments and exposure sources were almost always similarly identified but there were differences in estimating exposure duration. This occurred mainly when information collected from study subjects was not sufficiently detailed. Our results suggest that following a short training period and the availability of a clearly described method for estimating exposures, a non-expert can cost-efficiently and reliably assign exposure, at least to ELF-MF.
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http://dx.doi.org/10.1016/j.pmedr.2016.05.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4929127PMC
December 2016

Caesarean delivery and risk of childhood leukaemia: a pooled analysis from the Childhood Leukemia International Consortium (CLIC).

Lancet Haematol 2016 Apr 27;3(4):e176-85. Epub 2016 Feb 27.

Department of Pediatrics, University of Minnesota, MN, USA.

Background: Results from case-control studies have shown an increased risk of acute lymphoblastic leukaemia (ALL) in young children born by caesarean delivery, and prelabour caesarean delivery in particular; however, an association of method of delivery with childhood leukaemia subtypes has yet to be established. We therefore did a pooled analysis of data to investigate the association between childhood leukaemia and caesarean delivery.

Methods: We pooled data from 13 case-control studies from the Childhood Leukemia International Consortium done in nine countries (Canada, Costa Rica, Egypt, France, Germany, Greece, Italy, New Zealand, and the USA) for births from 1970-2013. We analysed caesarean delivery overall and by indications that probably resulted in prelabour caesarean delivery or emergency caesarean delivery. We used multivariable logistic regression models, adjusted for child's birthweight, sex, age, ethnic origin, parental education, maternal age, and study, to estimate odds ratios (ORs) and 95% CIs for the risk of ALL and acute myeloid leukaemia (AML) in children aged 0-14 years at diagnosis.

Findings: The studies provided data for 8780 ALL cases, 1332 AML cases, and 23 459 controls, of which the birth delivery method was known for 8655 (99%) ALL cases, 1292 (97%) AML cases, and 23 351 (>99%) controls. Indications for caesarean delivery were available in four studies (there were caesarean deliveries for 1061 of 4313 ALL cases, 138 of 664 AML cases, and 1401 of 5884 controls). The OR for all indications of caesarean delivery and ALL was 1·06 (95% CI 0·99-1·13), and was significant for prelabour caesarean delivery and ALL (1·23 [1·04-1·47]; p=0·018). Emergency caesarean delivery was not associated with ALL (OR 1·02 [95% CI 0·81-1·30]). AML was not associated with caesarean delivery (all indications OR 0·99 [95% CI 0·84-1·17]; prelabour caesarean delivery 0·83 [0·54-1·26]; and emergency caesarean delivery 1·05 [0·63-1·77]).

Interpretation: Our results suggest an increased risk of childhood ALL after prelabour caesarean delivery. If this association is causal, maladaptive immune activation due to an absence of stress response before birth in children born by prelabour caesarean delivery could be considered as a potential mechanism.

Funding: National Cancer Institute.
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http://dx.doi.org/10.1016/S2352-3026(16)00002-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5283076PMC
April 2016

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

Cancer Causes Control 2015 Sep 2;26(9):1257-70. Epub 2015 Jul 2.

Section of Environment and Radiation, International Agency for Research on Cancer, 150 cours Albert Thomas, 69372, Lyon Cedex 08, France.

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.
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http://dx.doi.org/10.1007/s10552-015-0618-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5257283PMC
September 2015

Home pesticide exposures and risk of childhood leukemia: Findings from the childhood leukemia international consortium.

Int J Cancer 2015 Dec 26;137(11):2644-63. Epub 2015 Jun 26.

International Agency for Research on Cancer (IARC), Section of Environment and Radiation, Lyon, France.

Some previous studies have suggested that home pesticide exposure before birth and during a child's early years may increase the risk of childhood leukemia. To further investigate this, we pooled individual level data from 12 case-control studies in the Childhood Leukemia International Consortium. Exposure data were harmonized into compatible formats. Pooled analyses were undertaken using multivariable unconditional logistic regression. The odds ratio (ORs) for acute lymphoblastic leukemia (ALL) associated with any pesticide exposure shortly before conception, during pregnancy and after birth were 1.39 (95% confidence interval [CI]: 1.25, 1.55) (using 2,785 cases and 3,635 controls), 1.43 (95% CI: 1.32, 1.54) (5,055 cases and 7,370 controls) and 1.36 (95% CI: 1.23, 1.51) (4,162 cases and 5,179 controls), respectively. Corresponding ORs for risk of acute myeloid leukemia (AML) were 1.49 (95% CI: 1.02, 2.16) (173 cases and 1,789 controls), 1.55 (95% CI: 1.21, 1.99) (344 cases and 4,666 controls) and 1.08 (95% CI: 0.76, 1.53) (198 cases and 2,655 controls), respectively. There was little difference by type of pesticide used. The relative similarity in ORs between leukemia types, time periods and pesticide types may be explained by similar exposure patterns and effects across the time periods in ALL and AML, participants' exposure to multiple pesticides, or recall bias. Although some recall bias is likely, until a better study design can be found to investigate the associations between home pesticide use and childhood leukemia in an equally large sample, it would appear prudent to limit the use of home pesticides before and during pregnancy, and during childhood.
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http://dx.doi.org/10.1002/ijc.29631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4572913PMC
December 2015

Favourable IFNL3 genotypes are associated with spontaneous clearance and are differentially distributed in Aboriginals in Canadian HIV-hepatitis C co-infected individuals.

Int J Mol Sci 2015 Mar 20;16(3):6496-512. Epub 2015 Mar 20.

Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC H3A 1A2, Canada.

Canadian Aboriginals are reported to clear Hepatitis C (HCV) more frequently. We tested the association of spontaneous clearance and three single nucleotide polymorphisms (SNPs) near the Interferon-lambda 3 (IFNL3) gene (rs12979860, rs8099917, functional variant rs8103142) and compared the SNP frequencies between HIV-HCV co-infected whites and Aboriginals from the Canadian Co-infection Cohort. HCV treatment-naïve individuals with at least two HCV RNA tests were included (n = 538). A spontaneous clearance case was defined as someone with two consecutive HCV RNA-negative tests, at least six months apart. Data were analyzed using Cox proportional hazards adjusted for sex and ethnicity. Advantageous variants and haplotypes were more common in Aboriginals than Caucasians: 57% vs. 46% had the rs12979860 CC genotype, respectively; 58% vs. 48%, rs8103142 TT; 74% vs. 67%, the rs12979860 C allele; and 67% vs. 64% the TCT haplotype with three favourable alleles. The adjusted Hazard Ratios (95% CI) for spontaneous clearance were: rs12979860: 3.80 (2.20, 6.54); rs8099917: 5.14 (2.46, 10.72); and rs8103142: 4.36 (2.49, 7.62). Even after adjusting for rs12979860, Aboriginals and females cleared HCV more often, HR (95% CI) = 1.53 (0.89, 2.61) and 1.42 (0.79, 2.53), respectively. Our results suggest that favourable IFNL3 genotypes are more common among Aboriginals than Caucasians, and may partly explain the higher HCV clearance rates seen among Aboriginals.
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http://dx.doi.org/10.3390/ijms16036496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394544PMC
March 2015

Childhood acute lymphoblastic leukemia and indicators of early immune stimulation: a Childhood Leukemia International Consortium study.

Am J Epidemiol 2015 Apr 1;181(8):549-62. Epub 2015 Mar 1.

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.
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http://dx.doi.org/10.1093/aje/kwu298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4850899PMC
April 2015

Maternal supplementation with folic acid and other vitamins and risk of leukemia in offspring: a Childhood Leukemia International Consortium study.

Epidemiology 2014 Nov;25(6):811-22

From the aUniversity of California, School of Public Health, Berkeley, CA; bTelethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, West Perth, Western Australia; cDean's Department and Department of Preventive and Social Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand; dInserm, CESP Centre for Research in Epidemiology and Population Health, Environmental Epidemiology of Cancer Team, Université Paris-Sud, Villejuif, France; ePediatric Hematology-Oncology Program, Research Program, Instituto Nacional de Cancer, Rio de Janeiro, Brazil; fInstituto Regional de Estudios en Sustancias Tóxicas (IRET), Universidad Nacional, Heredia, Costa Rica; gDivision of Epidemiology Clinical Research, Department of Pediatrics and Masonic Cancer Center, University of Minnesota, Minneapolis, MN; hInternational Agency for Research on Cancer, Section of Environment and Radiation, Lyon, France; iDepartment of Hygiene, Epidemiology, and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece; jResearch Department, Children's Cancer Hospital, Cairo, Egypt; kSydney School of Public Health, University of Sydney, New South Wales, Australia; lNational School of Public Health, Oswaldo Cruz Foundation (FIOCRUZ), Ministry of Health, Rio de Janeiro, Brazil; mGerman Childhood Cancer Registry, Institute for Medical Biostatistics, Epidemiology and Informatics, University Medical Centre, Johannes Gutenberg University Mainz, Mainz, Germany; nLunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada; and oDepartment of Epidemiology, Biostatistics, and Occupational Health, Faculty of Medicine, McGill University, Montréal, Province of Québec, Canada.

Background: Maternal prenatal supplementation with folic acid and other vitamins has been inconsistently associated with a reduced risk of childhood acute lymphoblastic leukemia (ALL). Little is known regarding the association with acute myeloid leukemia (AML), a rarer subtype.

Methods: We obtained original data on prenatal use of folic acid and vitamins from 12 case-control studies participating in the Childhood Leukemia International Consortium (enrollment period: 1980-2012), including 6,963 cases of ALL, 585 cases of AML, and 11,635 controls. Logistic regression was used to estimate pooled odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for child's age, sex, ethnicity, parental education, and study center.

Results: Maternal supplements taken any time before conception or during pregnancy were associated with a reduced risk of childhood ALL; odds ratios were 0.85 (95% CI = 0.78-0.92) for vitamin use and 0.80 (0.71-0.89) for folic acid use. The reduced risk was more pronounced in children whose parents' education was below the highest category. The analyses for AML led to somewhat unstable estimates; ORs were 0.92 (0.75-1.14) and 0.68 (0.48-0.96) for prenatal vitamins and folic acid, respectively. There was no strong evidence that risks of either types of leukemia varied by period of supplementation (preconception, pregnancy, or trimester).

Conclusions: Our results, based on the largest number of childhood leukemia cases to date, suggest that maternal prenatal use of vitamins and folic acid reduces the risk of both ALL and AML and that the observed association with ALL varied by parental education, a surrogate for lifestyle and sociodemographic characteristics.
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http://dx.doi.org/10.1097/EDE.0000000000000141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5903563PMC
November 2014

Reproductive factors and non-Hodgkin lymphoma: a systematic review.

Crit Rev Oncol Hematol 2014 Dec 30;92(3):181-93. Epub 2014 Jul 30.

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

Considerable efforts have been made to elucidate non-Hodgkin lymphoma's (NHL) etiology during the last decades. Some evidence points to an association with reproductive factors, as incidence rates for most NHL subtypes are usually higher in men than in women, and several subtypes express hormonal receptors. Although the evidence is not compelling, some studies show an inverse association with gravidity. Associations with postmenopausal hormone therapy are usually derived from unopposed estrogen use, rather than for the combination of estrogen with progestin, but these findings vary by study design. Inconsistencies in the results are likely due to the complex relationship between reproductive, biological, and sociodemographic factors, as well as to study limitations. Elucidating the role of hormonal factors should provide clues for therapeutic options and public health decisions. We provide an overview of the available evidence on reproductive factors in NHL etiology, underscoring potential sources of discrepancies and bias.
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http://dx.doi.org/10.1016/j.critrevonc.2014.07.004DOI Listing
December 2014

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

Cancer Causes Control 2014 Oct 5;25(10):1351-67. Epub 2014 Aug 5.

Section of Environment and Radiation, International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372, Lyon Cedex 08, France,

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.
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http://dx.doi.org/10.1007/s10552-014-0441-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4845093PMC
October 2014

Parental occupational pesticide exposure and the risk of childhood leukemia in the offspring: findings from the childhood leukemia international consortium.

Int J Cancer 2014 Nov 4;135(9):2157-72. Epub 2014 Apr 4.

International Agency for Research on Cancer (IARC), Section of Environment and Radiation, 150 Cours Albert Thomas, Lyon Cedex 08, France.

Maternal occupational pesticide exposure during pregnancy and/or paternal occupational pesticide exposure around conception have been suggested to increase risk of leukemia in the offspring. With a view to providing insight in this area we pooled individual level data from 13 case-control studies participating in the Childhood Leukemia International Consortium (CLIC). Occupational data were harmonized to a compatible format. Pooled individual analyses were undertaken using unconditional logistic regression. Using exposure data from mothers of 8,236 cases, and 14,850 controls, and from fathers of 8,169 cases and 14,201 controls the odds ratio (OR) for maternal exposure during pregnancy and the risk of acute lymphoblastic leukemia (ALL) was 1.01 [95% confidence interval (CI) 0.78, 1.30] and for paternal exposure around conception 1.20 (95% 1.06, 1.38). For acute myeloid leukemia (AML), the OR for maternal exposure during pregnancy was 1.94 (CI 1.19, 3.18) and for paternal exposure around conception 0.91 (CI 0.66, 1.24.) based on data from 1,329 case and 12,141 control mothers, and 1,231 case and 11,383 control fathers. Our finding of a significantly increased risk of AML in the offspring with maternal exposure to pesticides during pregnancy is consistent with previous reports. We also found a slight increase in risk of ALL with paternal exposure around conception which appeared to be more evident in children diagnosed at the age of 5 years or more and those with T cell ALL which raises interesting questions on possible mechanisms.
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http://dx.doi.org/10.1002/ijc.28854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4845098PMC
November 2014

A data-smoothing approach to explore and test gene-environment interaction in case-parent trios.

Stat Appl Genet Mol Biol 2014 Apr;13(2):159-71

Complex traits result from an interplay between genes and environment. A better understanding of their joint effects can help refine understanding of the epidemiology of the trait. Various tests have been proposed to assess the statistical interaction between genes and the environment (G×E) in case-parent trio data. However, these tests can lose power when the form of G×E departs from that for which the test was developed. To address this limitation, we propose a data-smoothing approach to estimate and test G×E between a single nucleotide polymorphism and a continuous environmental covariate. For estimating G×E, we fit a generalized additive model using penalized likelihood. The resulting point- and interval-estimates of G×E lead to a graphical display, which can serve as a visualization tool for exploring the form of interaction. For testing G×E, we propose a permutation approach, which accounts for the extra uncertainty introduced by the smoothing process. We investigate the statistical properties of the proposed methods through simulation. We also illustrate the use of the approach with an example data set. We conclude that the approach is useful for exploring novel interactions in data-rich settings.
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http://dx.doi.org/10.1515/sagmb-2013-0023DOI Listing
April 2014

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

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

Transmission ratio distortion: review of concept and implications for genetic association studies.

Hum Genet 2013 Mar 15;132(3):245-63. Epub 2012 Dec 15.

Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC H3A 1A2, Canada.

Transmission ratio distortion (TRD) occurs when one of the two alleles from either parent is preferentially transmitted to the offspring. This leads to a statistical departure from the Mendelian law of inheritance, which states that each of the two parental alleles is transmitted to offspring with a probability of 0.5. A number of mechanisms are thought to induce TRD such as meiotic drive, gametic competition, and embryo lethality. TRD has been extensively studied in animals, but the prevalence of TRD in humans remains largely unknown. Nevertheless, understanding the TRD phenomenon and taking it into consideration in many aspects of human genetics has potential benefits that have not been sufficiently emphasized in the current literature. In this review, we discuss the importance of TRD in three distinct but related fields of genetics: developmental genetics which studies the genetic abnormalities in zygotic and embryonic development, statistical genetics/genetic epidemiology which utilizes population study designs and statistical models to interpret the role of genes in human health, and population genetics which is concerned with genetic diversity in populations in an evolutionary context. From the perspective of developmental genetics, studying TRD leads to the identification of the processes and mechanisms for differential survival observed in embryos. As a result, it is a genetic force which affects allele frequency at the population, as well as, at the organismal level. Therefore, it has implications on genetic diversity of the population over time. From the perspective of genetic epidemiology, the TRD influence on a marker locus is a confounding factor which has to be adequately dealt with to correctly interpret linkage or association study results. These aspects are developed in this review. In addition to these theoretical notions, a brief summary of the empirical evidence of the TRD phenomenon in human and mouse studies is provided. The objective of our paper is to show the potentially important role of TRD in many areas of genetics, and to create an incentive for future research.
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http://dx.doi.org/10.1007/s00439-012-1257-0DOI Listing
March 2013

Reliability of cancer family history reported by parents in a case-control study of childhood leukemia.

Cancer Causes Control 2012 Oct 8;23(10):1665-72. Epub 2012 Aug 8.

Department of Epidemiology, Biostatistics and Occupational Health, Faculty of Medicine, McGill University, 1110 Avenue des Pins, Ouest, Montréal, QC H3A 1A, Canada.

Purpose: To investigate the reliability of family history of cancer reported by parents of children with acute lymphoblastic leukemia (ALL) and parents of healthy control children.

Methods: A total of 301 parents were selected based on positive or negative family history of cancer at baseline, case-control status, and gender of the respondent (mother or father). Baseline responses were compared with responses at the second interview using the same questionnaire. Reliability was measured using proportion of overall agreement, Cohen's kappa, and Cronbach's alpha; a logistic regression model was also used to assess the role of the case-control status on overall agreement as the dependent variable.

Results: The overall agreement between interviews was high and similar for cases (85 %) and controls (86 %); there were no consistent effects of respondent gender, age at first interview, or time elapsed between interviews on agreement measures. Agreement measures did not materially vary according to whether respondents were reporting about their mothers, fathers, or siblings.

Conclusions: The study showed very good reliability of reporting family history among young parents of children affected with leukemia and parents of healthy control children.
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http://dx.doi.org/10.1007/s10552-012-0045-4DOI Listing
October 2012

Strategies for genetic association analyses combining unrelated case-control individuals and family trios.

Am J Epidemiol 2012 Jul 9;176(1):70-9. Epub 2012 May 9.

Maternal-Infant Care Research Centre, Mount Sinai Hospital, 700 University Avenue, Suite 8-500, Toronto, Ontario M5G 1X6, Canada.

In genetic association studies, analyses integrating data or estimates from unrelated case-control individuals and case trios (case offspring and their parents) can increase statistical power to identify disease susceptibility loci. Data on control trios may also be available, but how and when their use is advantageous is less familiar and is described here. In addition, the authors examine assumptions and properties of hybrid analyses combining association estimates from unrelated case-control individuals together with case and control family trios, focusing on low-prevalence disease. One such assumption is absence of population stratification bias (PSB), a potential source of confounding in case-control analyses. For detection of PSB, the authors discuss 4 possible tests that assess equality between individual-level and family-based estimates. Furthermore, a weighted framework is presented, in which estimates from analyses combining unrelated individuals and families (most powerful but subject to PSB) and family-based analyses (robust to PSB) are weighted according to the observed PSB test P value. In contrast to existing hybrid designs that combine individuals and families only if no significant PSB is detected, the weighted framework does not require specification of an arbitrary PSB testing level to establish significance. The statistical methods are evaluated using simulations and applied to a candidate gene study of childhood leukemia (Quebec Childhood Leukemia Study, 1980-2000).
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http://dx.doi.org/10.1093/aje/kwr494DOI Listing
July 2012

Adjusting for spurious gene-by-environment interaction using case-parent triads.

Stat Appl Genet Mol Biol 2012 Jan 6;11(2). Epub 2012 Jan 6.

Simon Fraser University.

In the case-parent trio design, unrelated children affected with a disease are genotyped along with their parents. Information may also be collected on environmental factors in the children. The design permits estimation and testing of genetic effects and gene-by-environment interaction. Recently, it has been demonstrated that when genotypes are measured at a non-causal test locus, population stratification can create spurious interaction. That is, the environmental factor can appear to modify the disease risk associated with genotypes at the test locus without modifying the disease risk of genotypes at the causal locus. One design-based approach that is robust to spurious interaction requires the environmental factor to also be available on an unaffected sibling of the affected child. We explore the source of spurious interaction and suggest an alternate approach that mitigates its effects using case-parent triads. Our approach is based on adjusting the risk model using ancestry informative markers or random markers measured on the affected child and does not require data on unaffected siblings. We apply an approach to generating case-parent data, implemented in a freely-available R package soon to be released on the Comprehensive R Archive Network (CRAN).
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http://dx.doi.org/10.2202/1544-6115.1714DOI Listing
January 2012

Exploration and comparison of methods for combining population- and family-based genetic association using the Genetic Analysis Workshop 17 mini-exome.

BMC Proc 2011 Nov 29;5 Suppl 9:S28. Epub 2011 Nov 29.

Department of Biostatistics, University of Kentucky College of Public Health, 121 Washington Avenue, Lexington, KY 40536, USA.

We examine the performance of various methods for combining family- and population-based genetic association data. Several approaches have been proposed for situations in which information is collected from both a subset of unrelated subjects and a subset of family members. Analyzing these samples separately is known to be inefficient, and it is important to determine the scenarios for which differing methods perform well. Others have investigated this question; however, no extensive simulations have been conducted, nor have these methods been applied to mini-exome-style data such as that provided by Genetic Analysis Workshop 17. We quantify the empirical power and false-positive rates for three existing methods applied to the Genetic Analysis Workshop 17 mini-exome data and compare relative performance. We use knowledge of the underlying data simulation model to make these assessments.
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http://dx.doi.org/10.1186/1753-6561-5-S9-S28DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3287863PMC
November 2011

Asthma and risk of brain cancer in children.

Cancer Causes Control 2012 Apr 26;23(4):617-23. Epub 2012 Feb 26.

Department of Epidemiology, Biostatistics and Occupational Health, Faculty of Medicine, McGill University, 1110 Pine Avenue West, Montréal, QC, H3A 1A3, Canada.

Purpose: Little is known about the causes of central nervous system tumors in children. An inverse association between asthma and brain cancer was found in adults, but there is a dearth of studies in children. The goal of this study was to evaluate the association between asthma and brain cancer in children.

Methods: Two hundred and seventy-two cases of children with brain tumor diagnosed between 0 and 14 years of age in the Province of Québec, Canada, between 1980 and 1999 and 272 incidence density-matched controls were included in the study. The parents of cases and controls were interviewed by phone using structured questionnaires. Besides asthma in children, family history of asthma, the presence of other atopies, and medication intake were also investigated. Conditional logistic regression was used to analyze the data.

Results: Brain tumor risk was decreased in children with asthma (OR, 0.55; CI 95%, 0.33-0.93), with eczema (OR, 0.52; CI 95%, 0.17-1.57), and with both asthma and eczema (OR, 0.76; CI 95%, 0.18-3.2). Maternal or sibling asthma did not modify the effect of asthma on central nervous system (CNS) tumors, while father's asthma seemed to increase the risk, but numbers were small. Antiasthma medications such as inhaled corticosteroid and beta agonists seemed to increase the risk of CNS tumors (OR for steroids, 2.55; CI 95%, 0.79-8.20 and OR for inhaled beta agonist, 1.62; CI 95%, 0.57-4.63).

Conclusions: This study strengthens the hypothesis of inverse association between asthma and brain cancer in children, but family history and medications for asthma need further investigation.
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http://dx.doi.org/10.1007/s10552-012-9928-7DOI Listing
April 2012

Novel associations between activating killer-cell immunoglobulin-like receptor genes and childhood leukemia.

Blood 2011 Aug 25;118(5):1323-8. Epub 2011 May 25.

Laboratory of Innate Immunity, University of Montreal, Montreal, QC, Canada.

Acute lymphoblastic leukemia of pre-B cells (pre-B ALL) is the most frequent form of leukemia affecting children in Western countries. Evidence is accumulating that genetic factors play an important role in conferring susceptibility/resistance to leukemia in children. In this regard, activating killer-cell immunoglobulin-like receptor (KIR) genes are of particular interest. Humans may inherit different numbers of the 6 distinct activating KIR genes. Little is known about the impact of this genetic variation on the innate susceptibility or resistance of humans to the development of B-ALL. We addressed this issue by performing a case-control study in Canadian children of white origin. Our results show that harboring activating KIR genes is associated with reduced risk for developing B-ALL in these children. Of the 6 activating KIR genes, KIR2DS2 was maximally associated with decreased risk for the disease (P = 1.14 × 10(-7)). Furthermore, our results showed that inheritance of a higher number of activating KIR genes was associated with significant reductions in risk for ALL in children. These results were also consistent across different ALL phenotypes, which included children with pre-T cell ALL. Our study provides novel insights concerning the pathogenesis of childhood leukemia in white children and has implications for the development of new immunotherapies for this cancer.
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http://dx.doi.org/10.1182/blood-2010-10-313791DOI Listing
August 2011