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Carcinogenesis Advance Access published online on October 27, 2006
Carcinogenesis, doi:10.1093/carcin/bgl196
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Published by Oxford University Press 2006
Received May 18, 2006
Revised October 5, 2006
Accepted October 8, 2006

MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION

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

Qing Lan 1 *, Tongzhang Zheng 2, Stephen Chanock 3, Yawei Zhang 2, Min Shen 1, Sophia S. Wang 1, Sonja I. Berndt 1, Shelia H. Zahm 1, Theodore R. Holford 2, Brian Leaderer 2, Meredith Yeager 1, Robert Welch 1, Dean Hosgood 1, Peter Boyle 4, and Nathaniel Rothman 1

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 Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA; Pediatric Oncology Branch, Center for Cancer Research, NCI, NIH, DHHS, Bethesda, Maryland, USA
4 International Agency for Research on Cancer, Lyon, France,

* To whom correspondence should be addressed.
Qing Lan, E-mail: qingl{at}mail.nih.gov


  Abstract

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.

Keywords: non-Hodgkin lymphoma; Single nucleotide polymorphisms; Caspase; Apoptosis.
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