|
|
Blood, Vol. 114, Issue 2, 264-267, July 9, 2009
Genetic variation in caspase genes and risk of non-Hodgkin lymphoma: a pooled analysis of 3 population-based case-control studies
Blood Lan et al.
114: 264
Supplementary materials for: Lan et al
Subjects. Our study population derived from pooling three independent population-based case-control studies, which have been described in detail previously: the National Cancer Institute-Surveillance Epidemiology and End Results (NCI-SEER) NHL Case-Control Study, 1,2 the Connecticut NHL Case-Control Study,3,4 and the New South Wales (NSW) NHL Case-Control Study.5,6 The NCI-SEER NHL study was conducted within the SEER registry catchment areas of Iowa, Detroit, Los Angeles and Seattle;2 the Connecticut NHL study was conducted among female residents of Connecticut;4 and the New South Wales (NSW) study was conducted among residents of New South Wales and the Australian Capital Territory, Australia.6 All three studies included first primary NHL cases only, and population controls that were frequency-matched to cases. The protocols for each study were approved at the Institutional Review Boards of the NCI and each SEER center for the NCI-SEER study; Yale University, the Connecticut Department of Public Health, and the NCI for the Connecticut study; and all participating institutions for the NSW study. All study participants provided informed consent. Selected characteristics for each study are presented in Table S1. NHL pathology classification. In the NCI-SEER study, all cases were histologically confirmed by the local diagnosing pathologist. In the Connecticut study, all cases were confirmed by central review of diagnostic slides by two independent expert hematopathologists. In the NSW study, all cases were histologically confirmed by the local diagnosing pathologist, and a confirmatory central pathology review was performed for cases judged to be <90% certain to be NHL on review of the diagnostic pathology report by an expert hematopathologist. NHL pathology subtypes were classified based on the World Health Organization classification using the International Lymphoma Epidemiology Consortium (InterLymph) guidelines.7 In the present analyses, we evaluated NHL overall and specific NHL subtypes. The four most common NHL subtypes: diffuse large B-cell lymphoma (DLBCL) (28%), follicular lymphoma (28%), marginal zone lymphoma (8%), and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (8%) were evaluated in this report (Tables S1, S4S8). Biological samples and DNA extraction. Study participants who did not provide a biologic specimen, did not have sufficient material for DNA extraction or sufficient DNA for genotyping, or whose genotyped sex was discordant from the questionnaire data were excluded from this analysis (Table S1). For the NCI-SEER study, DNA was extracted from blood clots or buffy coats using Puregene Autopure DNA extraction kits (Gentra Systems, Minneapolis, MN), and from buccal cell samples by phenol-chloroform extraction methods.8 Genotype frequencies for individuals who provided blood compared with buccal cells were equivalent.9 For the Connecticut study, DNA was extracted from the blood samples using phenol-chloroform extraction methods.8 For the NSW study, DNA was extracted from buffy coats using Qiagen QIAamp® DNA Blood Midi Kits. In total, 1961 cases and 1825 controls (1001 cases and 834 controls from the NCI-SEER, 436 cases and 517 controls from the Yale, and 524 cases and 474 controls from the NSW studies) were genotyped for this analysis. Genotyping. Genotyping was conducted at the National Cancer Institute Core Genotyping Facility (Advanced Technology Center, Gaithersburg, MD; http://snp500cancer.nci.nih.gov).10 The results reported here were obtained as part of a larger panel of 1536 SNPs genotyped as a GoldenGate assay. Tag SNPs were chosen from the designable set of common SNPs (minor allele frequency (MAF)>5%) genotyped in the Caucasian (CEU) population sample of the HapMap Project (Data Release 20/Phase II, NCBI Build 35 assembly, dbSNPb125) using the software Tagzilla (http://tagzilla.nci.nih.gov/), which implements a tagging algorithm based on the pairwise binning method of Carlson et al.11 For each gene, SNPs within the region spanning 20kb 5′ of the start of transcription (exon 1) to 10kb 3′ of the end of the last exon were grouped using a binning threshold of r2>0.8. When there were multiple transcripts available for genes, only the primary transcript was assessed. Quality control (QC), exclusions, and final analytic study population. SNPs with low completion rate (<90% of samples) were excluded by study (NCI-SEER blood samples: N=1; NCI-SEER buccal cell samples: N=4). QC duplicates and replicates from each study were genotyped, blinded to laboratory personnel. SNPs with concordance <95% in the study-specific QC samples were excluded for that study. We also excluded samples with a low completion rate (<90% of the full panel of 1536 tag SNPs; NCI-SEER: 11 cases, 6 controls; Connecticut: 2 controls; NSW: 4 cases, 9 controls). The final pooled analytic study population included 1946 cases and 1808 controls with data for 102 SNPs in or near the 12 candidate genes in this analysis (Tables S1, S2). Two Caspase SNPs (rs4647322 and rs3181163) showed departure from HWE at p < 0.01 among non-Hispanic Caucasian controls in the pooled study population. QC data check did not suggest any obvious genotyping error. These SNPs are included in this report and none were significantly associated with risk of NHL. All statistical analyses were conducted using SAS version 9.1 (SAS Institute, Cary, NC). REFERENCES 1. Chatterjee N, Hartge P, Cerhan JR et al. Risk of non-Hodgkins lymphoma and family history of lymphatic, hematologic, and other cancers. Cancer Epidemiol Biomarkers Prev. 2004;13:14151421.
2. Wang SS, Davis S, Cerhan JR et al. Polymorphisms in oxidative stress genes and risk for non-Hodgkin lymphoma. Carcinogenesis. 2006;27:18281834.
3. Zhang Y, Holford TR, Leaderer B et al. Hair-coloring product use and risk of non-Hodgkin's lymphoma: a population-based case-control study in Connecticut. Am J Epidemiol. 2004;159:148154.
4. Lan Q, Zheng T, Rothman N et al. Cytokine polymorphisms in the Th1/Th2 pathway and susceptibility to non-Hodgkin lymphoma. Blood. 2006.
5. Hughes AM, Armstrong BK, Vajdic CM et al. Pigmentary characteristics, sun sensitivity and non-Hodgkin lymphoma. Int J Cancer. 2004;110:429434.
6. Purdue MP, Lan Q, Kricker A et al. Polymorphisms in immune function genes and risk of non-Hodgkin lymphoma: findings from the New South Wales non-Hodgkin Lymphoma Study. Carcinogenesis. 2007;28:704712.
7. Morton LM, Turner JJ, Cerhan JR et al. Proposed classification of lymphoid neoplasms for epidemiologic research from the Pathology Working Group of the International Lymphoma Epidemiology Consortium (InterLymph). Blood. 2007;110:695708.
8. Garcia-Closas M, Egan KM, Abruzzo J et al. Collection of genomic DNA from adults in epidemiological studies by buccal cytobrush and mouthwash. Cancer Epidemiol Biomarkers Prev. 2001;10:687696.
9. Bhatti P, Sigurdson AJ, Wang SS et al. Genetic variation and willingness to participate in epidemiologic research: data from three studies. Cancer Epidemiol Biomarkers Prev. 2005;14:24492453.
10. Packer BR, Yeager M, Burdett L et al. SNP500Cancer: a public resource for sequence validation, assay development, and frequency analysis for genetic variation in candidate genes. Nucleic Acids Res. 2006;34:D617D621.
11. Carlson CS, Eberle MA, Rieder MJ et al. Selecting a maximally informative set of single-nucleotide polymorphisms for association analyses using linkage disequilibrium. Am J Hum Genet. 2004;74:106120.
Files in this Data Supplement:
- Table S1. Demographic and pathology characteristics of study participants in the NCI-SEER, Connecticut, and New South Wales NHL case-control studies, by study and pooled (XLS, 20 KB)
- Table S2. Characteristics of single nucleotide polymorphisms evaluated in 9 caspase-related gene regions (XLS, 22 KB)
- Table S3. Individual SNP results from pooled study population for NHL over all and by study* (XLS, 1.4 MB)
- Table S4. Individual SNP results from pooled study population for NHL by subtype* (XLS, 400 KB)
- Table S5. Individual SNP results from pooled study population for DLBCL and by study* (XLS, 279 KB)
- Table S6. Individual SNP results from pooled study population for follicular and by study* (XLS, 2.19 MB)
- Table S7. Individual SNP results from pooled study population for marginal zone lymphoma and by study* (XLS, 879 KB)
- Table S8. Individual SNP results from pooled study population for CLL/SLL and by study* (XLS, 619 KB)
- Table S9. Individual SNP results from pooled study population, non-Hispanic Caucasion, and by age and sex (XLS, 195 KB)
|
|
