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Blood, 9 July 2009, Vol. 114, No. 2, pp. 264-267.
Prepublished online as a Blood First Edition Paper on May 4, 2009; DOI 10.1182/blood-2009-01-198697.


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CLINICAL TRIALS AND OBSERVATIONS

Brief report

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

Qing Lan1, Lindsay M. Morton1, Bruce Armstrong2, Patricia Hartge1, Idan Menashe1, Tongzhang Zheng3, Mark P. Purdue1, James R. Cerhan4, Yawei Zhang3, Andrew Grulich5, Wendy Cozen6, Meredith Yeager7, Theodore R. Holford3, Claire M. Vajdic8, Scott Davis9, Brian Leaderer3, Anne Kricker2, Maryjean Schenk10, Shelia H. Zahm1, Nilanjan Chatterjee1, Stephen J. Chanock1,7, Nathaniel Rothman1, and Sophia S. Wang1

1 Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Rockville, MD; 2 School of Public Health, University of Sydney, Sydney, Australia; 3 Department of Epidemiology and Public Health, Yale School of Medicine, New Haven, CT; 4 Mayo Clinic, College of Medicine, Rochester, MN; 5 National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia; 6 Norris Comprehensive Cancer Center, University of Southern California, Los Angeles; 7 Core Genotyping Facility, Advanced Technology Center, NCI, NIH, DHHS, Gaithersburg, MD; 8 University of New South Wales Cancer Research Centre, Prince of Wales Clinical School, University of New South Wales, Sydney, Australia; 9 Fred Hutchinson Cancer Research Center and University of Washington, Seattle; and 10 Department of Family Medicine and Karmanos Cancer Institute, Wayne State University, Detroit, MI

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; ORCC = 2.13; P trend = .011); CASP9 rs4661636 (ORCT = 0.89; ORTT = 0.77; P trend = .011); and CASP1 rs1785882 (ORAT = 1.12; ORAA = 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.


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