期刊
AMERICAN JOURNAL OF EPIDEMIOLOGY
卷 171, 期 3, 页码 267-276出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/aje/kwp383
关键词
lymphoma; lymphoma; non-Hodgkin; lymphotoxin-alpha; meta-analysis; polymorphism; genetic; polymorphism; single nucleotide; tumor necrosis factor-alpha
资金
- National Institutes of Health (NIH) [CA104862, CA45614, CA89745, CA87014, NO1-CO-12400, CA92153]
- National Cancer Institute of Canada
- Canadian Institutes of Health Research
- Michael Smith Foundation for Health Research
- European Commission [QLK4-CT-2000-00422]
- NO1-CO-12400
- Compagnia di San Paolo-Programma Oncologia
- Jose Carreras Leukemia Foundation [DJCLS-R04/08]
- Federal Office for Radiation Protection [StSch4261, StSch4420]
- Fondo Investigaciones Sanitarias [PI040091, PI041467]
- Network for Research in Epidemiology and Public Health [03/09]
- Leukaemia Research Fund
- Health and Medical Research Council of Australia, the Cancer Council New South Wales, and the University of Sydney Medical Foundation Program
- NCI [CA62 006]
- Cancer Research, Ireland
In an International Lymphoma Epidemiology Consortium pooled analysis, polymorphisms in 2 immune-system-related genes, tumor necrosis factor (TNF) and interleukin-10 (IL10), were associated with non-Hodgkin lymphoma (NHL) risk. Here, 8,847 participants were added to previous data (patients diagnosed from 1989 to 2005 in 14 case-control studies; 7,999 cases, 8,452 controls) for testing of polymorphisms in the TNF -308G > A (rs1800629), lymphotoxin-alpha (LTA) 252A > G (rs909253), IL10 -3575T > A (rs1800890, rs1800896), and nucleotide-binding oligomerization domain containing 2 (NOD2) 3020insC (rs2066847) genes. Odds ratios were estimated for non-Hispanic whites and several ethnic subgroups using 2-sided tests. Consistent with previous findings, odds ratios were increased for new participant TNF -308A carriers (NHL: per-allele odds ratio (ORallelic) = 1.10, P-trend = 0.001; diffuse large B-cell lymphoma (DLBCL): ORallelic = 1.23, P-trend = 0.004). In the combined population, odds ratios were increased for TNF -308A carriers (NHL: ORallelic = 1.13, P-trend = 0.0001; DLBCL: ORallelic = 1.25, P-trend = 3.7 x 10(-6); marginal zone lymphoma: ORallelic = 1.35, P-trend = 0.004) and LTA 252G carriers (DLBCL: ORallelic = 1.12, P-trend = 0.006; mycosis fungoides: ORallelic = 1.44, P-trend = 0.015). The LTA 252A > G/TNF -308G > A haplotype containing the LTA/TNF variant alleles was strongly associated with DLBCL (P = 2.9 x 10(-8)). Results suggested associations between IL10 -3575T > A and DLBCL (P-trend = 0.02) and IL10 -1082A > G and mantle cell lymphoma (P-trend = 0.04). These findings strengthen previous results for DLBCL and the LTA 252A > G/TNF -308A locus and provide robust evidence that these TNF/LTA gene variants, or others in linkage disequilibrium, are involved in NHL etiology.
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