Risk of non-Hodgkin lymphoma associated with germline variation in genes that regulate the cell cycle, apoptosis, and lymphocyte development

Lindsay M. Morton, Mark P. Purdue, Tongzhang Zheng, Sophia S. Wang, Bruce Armstrong, Yawei Zhang, Idan Menashe, Nilanjan Chatterjee, Scott Davis, Qing Lan, Claire M. Vajdic, Richard K. Severson, Theodore R. Holford, Anne Kricker, James R Cerhan, Brian Leaderer, Andrew Grulich, Meredith Yeager, Wendy Cozen, Shelia Hoar ZahmStephen J. Chanock, Nathaniel Rothman, Patricia Hartge

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Abstract

Chromosomal translocations are the hallmark genetic aberration in non-Hodgkin lymphoma (NHL), with specific translocations often selectively associated with specific NHL subtypes. Because many NHL-associated translocations involve cell cycle, apoptosis, and lymphocyte development regulatory genes, we evaluated NHL risk associated with common genetic variation in 20 candidate genes in these pathways. Genotyping of 203ta g single nucleotide polymorphisms (SNP) was conducted in 1,946 NHL cases and 1,808 controls pooled from 3in dependent population-based case-control studies. We used logistic regression to compute odds ratios (OR) and 95% confidence intervals (CI) for NHL and four major NHL subtypes in relation to tag SNP genotypes and haplotypes. We observed the most striking associations for tag SNPs in the proapoptotic gene BCL2L11 (BIM) and BCL7A, which is involved in a rare NHL-associated translocation. Variants in BCL2L11 were strongly related to follicular lymphoma only, particularly rs3789068 (ORAG, 1.41; 95% CI, 1.10-1.81; ORGG, 1.65; 95% CI, 1.25-2.19; Ptrend = 0.0004). Variants in BCL7A were strongly related to diffuse large B-cell lymphoma only, particularly rs1880030 (ORAG, 1.34; 95% CI, 1.08-1.68; ORAA, 1.60; 95% CI, 1.22-2.08; Ptrend = 0.0004). The associations for both variants were similar in all three studies and supported by haplotype analyses. We also observed notable associations for variants in BCL6, CCND1, and MYC. Our results support the role of common genetic variation in cell cycle, apoptosis, and lymphocyte development regulatory genes in lymphomagenesis, and suggest that effects may vary by NHL subtype. Replication of our findings and further study to identify functional SNPs are warranted.

Original languageEnglish (US)
Pages (from-to)1259-1270
Number of pages12
JournalCancer Epidemiology Biomarkers and Prevention
Volume18
Issue number4
DOIs
StatePublished - Apr 2009

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cdc Genes
Non-Hodgkin's Lymphoma
Lymphocytes
Apoptosis
Single Nucleotide Polymorphism
Confidence Intervals
Regulator Genes
Haplotypes
Cell Cycle
Genetic Translocation
Follicular Lymphoma
Lymphoma, Large B-Cell, Diffuse
Genes
Case-Control Studies
Logistic Models
Odds Ratio
Genotype

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Risk of non-Hodgkin lymphoma associated with germline variation in genes that regulate the cell cycle, apoptosis, and lymphocyte development. / Morton, Lindsay M.; Purdue, Mark P.; Zheng, Tongzhang; Wang, Sophia S.; Armstrong, Bruce; Zhang, Yawei; Menashe, Idan; Chatterjee, Nilanjan; Davis, Scott; Lan, Qing; Vajdic, Claire M.; Severson, Richard K.; Holford, Theodore R.; Kricker, Anne; Cerhan, James R; Leaderer, Brian; Grulich, Andrew; Yeager, Meredith; Cozen, Wendy; Zahm, Shelia Hoar; Chanock, Stephen J.; Rothman, Nathaniel; Hartge, Patricia.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 18, No. 4, 04.2009, p. 1259-1270.

Research output: Contribution to journalArticle

Morton, LM, Purdue, MP, Zheng, T, Wang, SS, Armstrong, B, Zhang, Y, Menashe, I, Chatterjee, N, Davis, S, Lan, Q, Vajdic, CM, Severson, RK, Holford, TR, Kricker, A, Cerhan, JR, Leaderer, B, Grulich, A, Yeager, M, Cozen, W, Zahm, SH, Chanock, SJ, Rothman, N & Hartge, P 2009, 'Risk of non-Hodgkin lymphoma associated with germline variation in genes that regulate the cell cycle, apoptosis, and lymphocyte development', Cancer Epidemiology Biomarkers and Prevention, vol. 18, no. 4, pp. 1259-1270. https://doi.org/10.1158/1055-9965.EPI-08-1037
Morton, Lindsay M. ; Purdue, Mark P. ; Zheng, Tongzhang ; Wang, Sophia S. ; Armstrong, Bruce ; Zhang, Yawei ; Menashe, Idan ; Chatterjee, Nilanjan ; Davis, Scott ; Lan, Qing ; Vajdic, Claire M. ; Severson, Richard K. ; Holford, Theodore R. ; Kricker, Anne ; Cerhan, James R ; Leaderer, Brian ; Grulich, Andrew ; Yeager, Meredith ; Cozen, Wendy ; Zahm, Shelia Hoar ; Chanock, Stephen J. ; Rothman, Nathaniel ; Hartge, Patricia. / Risk of non-Hodgkin lymphoma associated with germline variation in genes that regulate the cell cycle, apoptosis, and lymphocyte development. In: Cancer Epidemiology Biomarkers and Prevention. 2009 ; Vol. 18, No. 4. pp. 1259-1270.
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AU - Purdue, Mark P.

AU - Zheng, Tongzhang

AU - Wang, Sophia S.

AU - Armstrong, Bruce

AU - Zhang, Yawei

AU - Menashe, Idan

AU - Chatterjee, Nilanjan

AU - Davis, Scott

AU - Lan, Qing

AU - Vajdic, Claire M.

AU - Severson, Richard K.

AU - Holford, Theodore R.

AU - Kricker, Anne

AU - Cerhan, James R

AU - Leaderer, Brian

AU - Grulich, Andrew

AU - Yeager, Meredith

AU - Cozen, Wendy

AU - Zahm, Shelia Hoar

AU - Chanock, Stephen J.

AU - Rothman, Nathaniel

AU - Hartge, Patricia

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