Genetic variation in chromosomal translocation breakpoint and immune function genes and risk of non-Hodgkin lymphoma.
BACKGROUND
Tumor necrosis factor (TNF) and interleukin 10 (IL10) are promising candidate susceptibility genes for non-Hodgkin lymphoma (NHL). Chromosomal translocation breakpoint genes are of interest, given their documented involvement in lymphoma progression.


METHODS
We analyzed 11 polymorphisms in BCL2, CCND1, MYC, TNF, and IL10 in a large, population-based, Danish-Swedish case-control study including 2,449 NHL cases and 1,980 controls. Relative risk of NHL was computed as odds ratios (OR).


RESULTS
There was no clear evidence of associations between variants in BCL2, CCND1, and MYC and risk of NHL overall or subtypes. TNF rs1800629 was associated with risk of NHL (OR 1.53, 95% confidence interval, CI, 1.06-2.19 for minor allele homozygosity), T-cell lymphoma (OR 2.54, CI 1.27-5.09) and mantle cell lymphoma (OR 2.84, CI 1.38-5.87). IL10 rs1800890 was associated with risk of diffuse large B-cell lymphoma (OR 1.41, CI 1.08-1.85 for minor allele homozygosity) and mantle cell lymphoma (OR 1.77, CI 1.04-3.00). We did not replicate a previously reported interaction with autoimmunity.


CONCLUSIONS
We found no support for a role of the studied variants in BCL2, CCND1, or MYC in risk of NHL or subtypes, but we provide further evidence of putative susceptibility loci in TNF and IL10 for specific NHL subtypes.
Fernberg
Pia
P
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. pia.fernberg@ki.se
Chang
Ellen T
ET
Duvefelt
Kristina
K
Hjalgrim
Henrik
H
Eloranta
Sandra
S
Sørensen
Karina Meden
KM
Porwit
Anna
A
Humphreys
Keith
K
Melbye
Mads
M
Ekström Smedby
Karin
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D019938:Cyclin D1 / Q000235:genetics; D005260:Female; D019254:Genes, bcl-2 / Q000235:genetics; D016259:Genes, myc / Q000235:genetics; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D014178:Translocation, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D055815:Young Adult
C530104:CCND1 protein, human; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D019938:Cyclin D1