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Carcinogenesis Advance Access originally published online on October 27, 2006
Carcinogenesis 2007 28(4):823-827; doi:10.1093/carcin/bgl196
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Published by Oxford University Press 2006

Genetic variants in caspase genes and susceptibility to non-Hodgkin lymphoma

Qing Lan1,*, Tongzhang Zheng2, Stephen Chanock1,3, Yawei Zhang2, Min Shen1, Sophia S. Wang1, Sonja I. Berndt1, Shelia H. Zahm1, Theodore R. Holford2, Brian Leaderer2, Meredith Yeager1, Robert Welch1, Dean Hosgood1, Peter Boyle4 and Nathaniel Rothman1

1 Division of Cancer Epidemiology and Genetics, National Cancer Institute NIH, DHHS, Bethesda, MD, USA
2 Department of Epidemiology and Public Health, Yale School of Medicine New Haven, USA
3 Pediatric Oncology Branch, Center for Cancer Research NCI, NIH, DHHS, Bethesda, MD, USA
4 International Agency for Research on Cancer Lyon, France

*To whom correspondence should be addressed at: Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, MSC 7240, 6120 Executive Boulevard, EPS 8109, Bethesda, MD 20892-7240, USA. Tel: +1 301 435 4706; Fax: +1 301 402 1819 Email: qingl{at}mail.nih.gov

The caspase proteins are essential for the regulation of normal B cell development and regulation of apoptosis. We investigated five single nucleotide polymorphisms in four key caspase genes, CASP3 [Ex8-280C>A (rs6948) and Ex8+567T>C (rs1049216)], CASP8 Ex14-271A>T (rs13113), CASP9 Ex5+32G>A (rs1052576) and CASP10 Ex3-171A>G (rs3900115) to determine whether they alter risk for non-Hodgkin lymphoma (NHL) in a population-based case–control study of women in Connecticut (461 cases and 535 controls). Variants in CASP3 and CASP9 were significantly associated with a decreased risk for NHL, particularly follicular lymphoma [e.g. CASP3 Ex8+567T>C odds ratio (OR)CC+TC = 0.4, 95% confidence interval (CI) = 0.3–0.7; and CASP9 Ex5+32G>A ORAA+AG = 0.6, 95% CI = 0.4–1.0]. Further, variants in CASP3, CASP8 and CASP10 were associated with a decreased risk of marginal zone lymphoma and variants in CASP3 and CASP10 were associated with a lower risk of chronic lymphocytic leukemia and related subtypes. The striking protective associations observed for polymorphisms in all four genes for NHL and/or one or more subtypes suggest that genetic variation in CASP genes may play an important role in the etiology of NHL.

Abbreviations: HWE, Hardy–Weinberg equilibrium; LD, linkage disequilibrium; NHL, non-Hodgkin lymphoma; SNP, single nucleotide polymorphisms

Received May 18, 2006; revised October 5, 2006; accepted October 8, 2006.


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