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Abstract

Title: Genetic variants in caspase genes and susceptibility to non-Hodgkin lymphoma.
Author: Lan Q, Zheng T, Chanock S, Zhang Y, Shen M, Wang SS, Berndt SI, Zahm SH, Holford TR, Leaderer B, Yeager M, Welch R, Hosgood D, Boyle P, Rothman N
Journal: Carcinogenesis 28(4):823-827
Year: 2006
Month: April

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.