Genetic variation in caspase genes and risk of non-Hodgkin lymphoma: a pooled analysis of 3 population-based case-control studies.
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; OR(CC) = 2.13; P trend = .011); CASP9 rs4661636 (OR(CT) = 0.89; OR(TT) = 0.77; P trend = .011); and CASP1 rs1785882 (OR(AT) = 1.12; OR(AA) = 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.
Lan
Qing
Q
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, MD, USA. qingl@mail.nih.gov
Morton
Lindsay M
LM
Armstrong
Bruce
B
Hartge
Patricia
P
Menashe
Idan
I
Zheng
Tongzhang
T
Purdue
Mark P
MP
Cerhan
James R
JR
Zhang
Yawei
Y
Grulich
Andrew
A
Cozen
Wendy
W
Yeager
Meredith
M
Holford
Theodore R
TR
Vajdic
Claire M
CM
Davis
Scott
S
Leaderer
Brian
B
Kricker
Anne
A
Schenk
Maryjean
M
Zahm
Shelia H
SH
Chatterjee
Nilanjan
N
Chanock
Stephen J
SJ
Rothman
Nathaniel
N
Wang
Sophia S
SS
D016022:Case-Control Studies; D020169:Caspases / Q000235:genetics* / Q000378:metabolism*; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000145:classification / Q000201:enzymology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors
D020169:Caspases