Genetic variants in caspase genes and susceptibility to non-Hodgkin lymphoma.
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 OR(AA+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.
Lan
Qing
Q
Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute NIH, DHHS, Bethesda, MD 20892-7240, USA. qingl@mail.nih.gov
Zheng
Tongzhang
T
Chanock
Stephen
S
Zhang
Yawei
Y
Shen
Min
M
Wang
Sophia S
SS
Berndt
Sonja I
SI
Zahm
Shelia H
SH
Holford
Theodore R
TR
Leaderer
Brian
B
Yeager
Meredith
M
Welch
Robert
R
Hosgood
Dean
D
Boyle
Peter
P
Rothman
Nathaniel
N
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D053455:Caspase 10 / Q000235:genetics*; D053148:Caspase 3 / Q000235:genetics*; D053181:Caspase 8 / Q000235:genetics*; D053453:Caspase 9 / Q000235:genetics*; D004260:DNA Repair; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053455:Caspase 10; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; C506438:CASP10 protein, human