Genetic variation in chromosomal translocation breakpoint and immune function genes and risk of non-Hodgkin lymphoma

• Published in: Cancer causes & control 2010-05, Vol.21 (5), p.759-769
• Main Authors: Fernberg, Pia, Chang, Ellen T, Duvefelt, Kristina, Hjalgrim, Henrik, Eloranta, Sandra, Sørensen, Karina Meden, Porwit, Anna, Humphreys, Keith, Melbye, Mads, Ekström Smedby, Karin
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Autoimmune diseases; Biomedical and Life Sciences; Biomedicine; Blood; Cancer; Cancer Research; Case-Control Studies; Cell cycle; Cyclin D1 - genetics; Cytokines; DNA; Epidemiology; Female; Genes; Genes, bcl-2 - genetics; Genes, myc - genetics; Genetic variation; Genomics; Genotypes; Hardy Weinberg law; Hematology; HIV; Human immunodeficiency virus; Humans; Infections; Interleukin-10 - genetics; Interviews; Lymphoma; Lymphoma, Non-Hodgkin - genetics; Male; Mantle cell lymphoma; Middle Aged; Non Hodgkin lymphoma; Odds Ratio; Oncology; Original Paper; Polymorphism, Single Nucleotide; Public Health; Translocation, Genetic; Transplants & implants; Tumor Necrosis Factor-alpha - genetics; Tumor necrosis factor-TNF; Young Adult
• ISSN: 0957-5243; 1573-7225
• DOI: 10.1007/s10552-010-9504-y

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.