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.
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
Qing
Q
Lan
Lindsay M
LM
Morton
Bruce
B
Armstrong
Patricia
P
Hartge
Idan
I
Menashe
Tongzhang
T
Zheng
Mark P
MP
Purdue
James R
JR
Cerhan
Yawei
Y
Zhang
Andrew
A
Grulich
Wendy
W
Cozen
Meredith
M
Yeager
Theodore R
TR
Holford
Claire M
CM
Vajdic
Scott
S
Davis
Brian
B
Leaderer
Anne
A
Kricker
Maryjean
M
Schenk
Shelia H
SH
Zahm
Nilanjan
N
Chatterjee
Stephen J
SJ
Chanock
Nathaniel
N
Rothman
Sophia S
SS
Wang
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