Common genetic variants in candidate genes and risk of familial lymphoid malignancies.
Familial aggregation, linkage and case-control studies support the role of germline genes in the aetiology of lymphoid malignancies. To further examine the role of genetic variation underlying susceptibility, we analysed 1536 single nucleotide polymorphisms in 152 genes involved in apoptosis, DNA repair, immune response and oxidative stress pathways among a unique sample of 165 unrelated familial cases including patients with chronic lymphocytic leukaemia (CLL), Waldenström macroglobulinaemia (WM) and Hodgkin lymphoma (HL), and 107 spouse controls. We confirmed previous studies showing a polymorphism in the IL10 promoter (rs1800890/-3575T>A) to be associated with non-Hodgkin lymphoma, as this allele was found to be associated with both CLL and WM. We also confirmed the role of IL6 variation to be associated with HL. Polymorphisms in TNFSF10 were associated with both CLL and WM. Future replication and functional studies are needed to clarify the role of these genetic variants. Finally, our data further support the close association of WM and CLL.
Liang
Xueying Sharon
XS
Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892-7236, USA. liangx2@mail.nih.gov
Caporaso
Neil
N
McMaster
Mary Lou
ML
Ng
David
D
Landgren
Ola
O
Yeager
Meredith
M
Chanock
Stephen
S
Goldin
Lynn R
LR
D016022:Case-Control Studies; D045744:Cell Line, Tumor; D014644:Genetic Variation; D005838:Genotype; D006689:Hodgkin Disease / Q000235:genetics; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics; D016015:Logistic Models; D008232:Lymphoproliferative Disorders / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D012306:Risk; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics; D008258:Waldenstrom Macroglobulinemia / Q000235:genetics
D015850:Interleukin-6; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D016753:Interleukin-10