Mortality ascertainment of participants in the National Wilms Tumor Study using the National Death Index: comparison of active and passive follow-up results

Long term studies of childhood cancer survivors are hampered by difficulties in tracking young adult participants. After performing a National Death Index (NDI) search we sought to identify which factors best predicted a match among known decedents from the National Wilms Tumor Study (NWTS) and to determine if record linkage could substitute for missing follow-up in a cohort of NWTS survivors. To our knowledge, this is the first study to compare passive mortality follow-up using the NDI to active follow-up of a childhood and young adult population

Crude incidence in two-phase designs in the presence of competing risks.

BackgroundIn many studies, some information might not be available for the whole cohort, some covariates, or even the outcome, might be ascertained in selected subsamples. These studies are part of a broad category termed two-phase studies. Common examples include the nested case-control and the case-cohort designs. For two-phase studies, appropriate weighted survival estimates have been derived; however, no estimator of cumulative incidence accounting for competing events has been proposed. This is relevant in the presence of multiple types of events, where estimation of event type specific quantities are needed for evaluating outcome.MethodsWe develop a non parametric estimator of the cumulative incidence function of events accounting for possible competing events. It handles a general sampling design by weights derived from the sampling probabilities. The variance is derived from the influence function of the subdistribution hazard.ResultsThe proposed method shows good performance in simulations. It is applied to estimate the crude incidence of relapse in childhood acute lymphoblastic leukemia in groups defined by a genotype not available for everyone in a cohort of nearly 2000 patients, where death due to toxicity acted as a competing event. In a second example the aim was to estimate engagement in care of a cohort of HIV patients in resource limited setting, where for some patients the outcome itself was missing due to lost to follow-up. A sampling based approach was used to identify outcome in a subsample of lost patients and to obtain a valid estimate of connection to care.ConclusionsA valid estimator for cumulative incidence of events accounting for competing risks under a general sampling design from an infinite target population is derived

Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, intakes of folate and related B vitamins and colorectal cancer : a case-control study in a population with relatively low folate intake

Peer reviewedPublisher PD

Semiparametric regression methods for temporal processes subject to multiple sources of censoring

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155547/1/cjs11528.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155547/2/cjs11528_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155547/3/cjs11528-sup-0002-SuppInfo2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155547/4/cjs11528-sup-0001-SuppInfo1.pd

Are quantitative trait-dependent sampling designs cost-effective for analysis of rare and common variants?

Use of trait-dependent sampling designs in whole-genome association studies of sequence data can reduce total sequencing costs with modest losses of statistical efficiency. In a quantitative trait (QT) analysis of data from the Genetic Analysis Workshop 17 mini-exome for unrelated individuals in the Asian subpopulation, we investigate alternative designs that sequence only 50% of the entire cohort. In addition to a simple random sampling design, we consider extreme-phenotype designs that are of increasing interest in genetic association analysis of QTs, especially in studies concerned with the detection of rare genetic variants. We also evaluate a novel sampling design in which all individuals have a nonzero probability of being selected into the sample but in which individuals with extreme phenotypes have a proportionately larger probability. We take differential sampling of individuals with informative trait values into account by inverse probability weighting using standard survey methods which thus generalizes to the source population. In replicate 1 data, we applied the designs in association analysis of Q1 with both rare and common variants in the FLT1 gene, based on knowledge of the generating model. Using all 200 replicate data sets, we similarly analyzed Q1 and Q4 (which is known to be free of association with FLT1) to evaluate relative efficiency, type I error, and power. Simulation study results suggest that the QT-dependent selection designs generally yield greater than 50% relative efficiency compared to using the entire cohort, implying cost-effectiveness of 50% sample selection and worthwhile reduction of sequencing costs

Secondary Sex Ratio among Women Exposed to Diethylstilbestrol in Utero

BACKGROUND. Diethylstilbestrol (DES), a synthetic estrogen widely prescribed to pregnant women during the mid-1900s, is a potent endocrine disruptor. Previous studies have suggested an association between endocrine-disrupting compounds and secondary sex ratio. METHODS. Data were provided by women participating in the National Cancer Institute (NCI) DES Combined Cohort Study. We used generalized estimating equations to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the relation of in utero DES exposure to sex ratio (proportion of male births). Models were adjusted for maternal age, child's birth year, parity, and cohort, and accounted for clustering among women with multiple pregnancies. RESULTS. The OR for having a male birth comparing DES-exposed to unexposed women was 1.05 (95% CI, 0.95-1.17). For exposed women with complete data on cumulative DES dose and timing (33%), those first exposed to DES earlier in gestation and to higher doses had the highest odds of having a male birth. The ORs were 0.91 (95% C, 0.65-1.27) for first exposure at ≥ 13 weeks gestation to < 5 g DES; 0.95 (95% CI, 0.71-1.27) for first exposure at ≥ 13 weeks to ≥ 5 g; 1.16 (95% CI, 0.96-1.41) for first exposure at < 13 weeks to < 5 g; and 1.24 (95% CI, 1.04-1.48) for first exposure at < 13 weeks to ≥ 5 g compared with no exposure. Results did not vary appreciably by maternal age, parity, cohort, or infertility history. CONCLUSIONS. Overall, no association was observed between in utero DES exposure and secondary sex ratio, but a significant increase in the proportion of male births was found among women first exposed to DES earlier in gestation and to a higher cumulative dose.National Cancer Institute (N01-CP-21168, N01-CP-51017, N01-CP-01289

Household Pesticides and the Risk of Wilms Tumor

BACKGROUND: Previous epidemiologic studies have suggested that exposure to pesticides in utero and during early childhood may increase the risk for development of childhood cancer, including Wilms tumor, a childhood kidney tumor. OBJECTIVES: In this analysis we evaluated the role of residential pesticide exposure in relation to the risk of Wilms tumor in children using data from a North American case–control study. METHODS: The National Wilms Tumor Study Group (NWTSG) collected information on exposure to residential pesticides from the month before pregnancy through the diagnosis reference date using detailed phone interviews from 523 case mothers and 517 controls frequency matched on child’s age and geographic region and identified by list-assisted random digit dialing. Pesticides were grouped according to type of pesticide and where they were used. RESULTS: A slightly increased risk of Wilms tumor was found among children of mothers who reported insecticide use [odds ratio (OR) = 1.4, 95% confidence interval (CI), 1.0–1.8; adjusted for education, income, and the matching variables]. Results from all other categories of pesticides were generally close to the null. CONCLUSIONS: This study is the largest case–control study of Wilms tumor to date. We were unable to confirm earlier reports of an increased risk for Wilms tumor among those exposed to residential pesticides during pregnancy through early childhood