Dataset Information

Genetic variation in caspase genes and risk of non-Hodgkin lymphoma: a pooled analysis of 3 population-based case-control studies.

ABSTRACT: Caspases play a critical role in regulation of apoptosis, cell differentiation, inflammation, and innate immunity, and several are mutated or have altered expression in non-Hodgkin lymphoma (NHL). To study the impact of genetic variation in caspases on NHL risk, we analyzed tag single nucleotide polymorphisms (SNPs) in 12 caspase and related genes in 3 population-based case-control studies (1946 cases and 1808 controls). Gene-based analysis, adjusting for the number of tagSNPs genotyped in each gene, showed significant associations for CASP8, CASP9, and CASP1. SNP-based analysis showed that CASP8 rs6736233 (odds ratio (OR) (CG) = 1.21; OR(CC) = 2.13; P trend = .011); CASP9 rs4661636 (OR(CT) = 0.89; OR(TT) = 0.77; P trend = .011); and CASP1 rs1785882 (OR(AT) = 1.12; OR(AA) = 1.30; P trend = .0054) were significantly associated with NHL risk and consistent across studies. It is noteworthy that genetic variants in CASP8 were associated with risk of all major NHL subtypes. Our findings suggest that genetic variation in caspases may play an important role in lymphomagenesis.

SUBMITTER: Lan Q

PROVIDER: S-EPMC2714202 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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Genetic variation in caspase genes and risk of non-Hodgkin lymphoma: a pooled analysis of 3 population-based case-control studies.

Lan Qing Q Morton Lindsay M LM Armstrong Bruce B Hartge Patricia P Menashe Idan I Zheng Tongzhang T Purdue Mark P MP Cerhan James R JR Zhang Yawei Y Grulich Andrew A Cozen Wendy W Yeager Meredith M Holford Theodore R TR Vajdic Claire M CM Davis Scott S Leaderer Brian B Kricker Anne A Schenk Maryjean M Zahm Shelia H SH Chatterjee Nilanjan N Chanock Stephen J SJ Rothman Nathaniel N Wang Sophia S SS

Blood 20090504 2

Caspases play a critical role in regulation of apoptosis, cell differentiation, inflammation, and innate immunity, and several are mutated or have altered expression in non-Hodgkin lymphoma (NHL). To study the impact of genetic variation in caspases on NHL risk, we analyzed tag single nucleotide polymorphisms (SNPs) in 12 caspase and related genes in 3 population-based case-control studies (1946 cases and 1808 controls). Gene-based analysis, adjusting for the number of tagSNPs genotyped in each ...[more]

PMID: 19414860

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Project description:ObjectivesOccupational exposures in population-based case-control studies are increasingly being assessed using decision rules that link participants' responses to occupational questionnaires to exposure estimates. We used a hierarchical process that incorporated decision rules and job-by-job expert review to assign occupational benzene exposure estimates in a US population-based case-control study of non-Hodgkin lymphoma.MethodsWe conducted a literature review to identify scenarios in which occupational benzene exposure has occurred, which we grouped into 12 categories of benzene exposure sources. For each source category, we then developed decision rules for assessing probability (ordinal scale based on the likelihood of exposure > 0.02 ppm), frequency (proportion of work time exposed), and intensity of exposure (in ppm). The rules used the participants' occupational history responses and, for a subset of jobs, responses to job- and industry-specific modules. For probability and frequency, we used a hierarchical assignment procedure that prioritized subject-specific module information when available. Next, we derived job-group medians from the module responses to assign estimates to jobs with only occupational history responses. Last, we used job-by-job expert review to assign estimates when job-group medians were not available or when the decision rules identified possible heterogeneous or rare exposure scenarios. For intensity, we developed separate estimates for each benzene source category that were based on published measurement data whenever possible. Frequency and intensity annual source-specific estimates were assigned only for those jobs assigned ≥75% probability of exposure. Annual source-specific concentrations (intensity × frequency) were summed to obtain a total annual benzene concentration for each job.ResultsOf the 8827 jobs reported by participants, 8% required expert review for one or more source categories. Overall, 287 (3.3%) jobs were assigned ≥75% probability of exposure from any benzene source category. The source categories most commonly assigned ≥75% probability of exposure were gasoline and degreasing. The median total annual benzene concentration among jobs assigned ≥75% probability was 0.11 ppm (interquartile range: 0.06-0.55). The highest source-specific median annual concentrations were observed for ink and printing (2.3 and 1.2 ppm, respectively).ConclusionsThe applied framework captures some subject-specific variability in work tasks, provides transparency to the exposure decision process, and facilitates future sensitivity analyses. The developed decision rules can be used as a starting point by other researchers to assess occupational benzene exposure in future population-based studies.

Dataset Information

Genetic variation in caspase genes and risk of non-Hodgkin lymphoma: a pooled analysis of 3 population-based case-control studies.

Publications

Genetic variation in caspase genes and risk of non-Hodgkin lymphoma: a pooled analysis of 3 population-based case-control studies.

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