TY - JOUR
T1 - Genetic variation in TNF and IL10 and risk of non-Hodgkin lymphoma
T2 - a report from the InterLymph Consortium
AU - Rothman, Nathaniel
AU - Skibola, Christine F
AU - Wang, Sophia S
AU - Morgan, Gareth
AU - Lan, Qing
AU - Smith, Martyn T
AU - Spinelli, John J
AU - Willett, Eleanor
AU - De Sanjose, Silvia
AU - Cocco, Pierluigi
AU - Berndt, Sonja I
AU - Brennan, Paul
AU - Brooks-Wilson, Angela
AU - Wacholder, Sholom
AU - Becker, Nikolaus
AU - Hartge, Patricia
AU - Zheng, Tongzhang
AU - Roman, Eve
AU - Holly, Elizabeth A
AU - Boffetta, Paolo
AU - Armstrong, Bruce
AU - Cozen, Wendy
AU - Linet, Martha
AU - Bosch, F Xavier
AU - Ennas, Maria Grazia
AU - Holford, Theodore R
AU - Gallagher, Richard P
AU - Rollinson, Sara
AU - Bracci, Paige M
AU - Cerhan, James R
AU - Whitby, Denise
AU - Moore, Patrick S
AU - Leaderer, Brian
AU - Lai, Agnes
AU - Spink, Charlotte
AU - Davis, Scott
AU - Bosch, Ramon
AU - Scarpa, Aldo
AU - Zhang, Yawei
AU - Severson, Richard K
AU - Yeager, Meredith
AU - Chanock, Stephen
AU - Nieters, Alexandra
PY - 2006/1
Y1 - 2006/1
N2 - BACKGROUND: Common genetic variants in immune and inflammatory response genes can affect the risk of developing non-Hodgkin lymphoma. We aimed to test this hypothesis using previously unpublished data from eight European, Canadian, and US case-control studies of the International Lymphoma Epidemiology Consortium (InterLymph).METHODS: We selected 12 single-nucleotide polymorphisms for analysis, on the basis of previous functional or association data, in nine genes that have important roles in lymphoid development, Th1/Th2 balance, and proinflammatory or anti-inflammatory pathways (IL1A, IL1RN, IL1B, IL2, IL6, IL10, TNF, LTA, and CARD15). Genotype data for one or more single-nucleotide polymorphisms were available for 3586 cases of non-Hodgkin lymphoma and for 4018 controls, and were assessed in a pooled analysis by use of a random-effects logistic regression model.FINDINGS: The tumour necrosis factor (TNF) -308G-->A polymorphism was associated with increased risk of non-Hodgkin lymphoma (p for trend=0.005), particularly for diffuse large B-cell lymphoma, the main histological subtype (odds ratio 1.29 [95% CI 1.10-1.51] for GA and 1.65 [1.16-2.34] for AA, p for trend <0.0001), but not for follicular lymphoma. The interleukin 10 (IL10) -3575T-->A polymorphism was also associated with increased risk of non-Hodgkin lymphoma (p for trend=0.02), again particularly for diffuse large B-cell lymphoma (p for trend=0.006). For individuals homozygous for the TNF -308A allele and carrying at least one IL10 -3575A allele, risk of diffuse large B-cell lymphoma doubled (2.13 [1.37-3.32], p=0.00083).INTERPRETATION: Common polymorphisms in TNF and IL10, key cytokines for the inflammatory response and Th1/Th2 balance, could be susceptibility loci for non-Hodgkin lymphoma. Moreover, our results underscore the importance of consortia for investigating the genetic basis of chronic diseases like cancer.
AB - BACKGROUND: Common genetic variants in immune and inflammatory response genes can affect the risk of developing non-Hodgkin lymphoma. We aimed to test this hypothesis using previously unpublished data from eight European, Canadian, and US case-control studies of the International Lymphoma Epidemiology Consortium (InterLymph).METHODS: We selected 12 single-nucleotide polymorphisms for analysis, on the basis of previous functional or association data, in nine genes that have important roles in lymphoid development, Th1/Th2 balance, and proinflammatory or anti-inflammatory pathways (IL1A, IL1RN, IL1B, IL2, IL6, IL10, TNF, LTA, and CARD15). Genotype data for one or more single-nucleotide polymorphisms were available for 3586 cases of non-Hodgkin lymphoma and for 4018 controls, and were assessed in a pooled analysis by use of a random-effects logistic regression model.FINDINGS: The tumour necrosis factor (TNF) -308G-->A polymorphism was associated with increased risk of non-Hodgkin lymphoma (p for trend=0.005), particularly for diffuse large B-cell lymphoma, the main histological subtype (odds ratio 1.29 [95% CI 1.10-1.51] for GA and 1.65 [1.16-2.34] for AA, p for trend <0.0001), but not for follicular lymphoma. The interleukin 10 (IL10) -3575T-->A polymorphism was also associated with increased risk of non-Hodgkin lymphoma (p for trend=0.02), again particularly for diffuse large B-cell lymphoma (p for trend=0.006). For individuals homozygous for the TNF -308A allele and carrying at least one IL10 -3575A allele, risk of diffuse large B-cell lymphoma doubled (2.13 [1.37-3.32], p=0.00083).INTERPRETATION: Common polymorphisms in TNF and IL10, key cytokines for the inflammatory response and Th1/Th2 balance, could be susceptibility loci for non-Hodgkin lymphoma. Moreover, our results underscore the importance of consortia for investigating the genetic basis of chronic diseases like cancer.
KW - Case-Control Studies
KW - Genetic Predisposition to Disease
KW - Genotype
KW - Humans
KW - Inflammation
KW - Interleukin-10
KW - Lymphoma, Non-Hodgkin
KW - Pedigree
KW - Polymorphism, Single Nucleotide
KW - Risk Factors
KW - Tumor Necrosis Factor-alpha
KW - Journal Article
KW - Research Support, N.I.H., Extramural
KW - Research Support, N.I.H., Intramural
KW - Research Support, Non-U.S. Gov't
UR - https://www.scopus.com/pages/publications/29744459902
U2 - 10.1016/S1470-2045(05)70434-4
DO - 10.1016/S1470-2045(05)70434-4
M3 - Article
C2 - 16389181
SN - 1470-2045
VL - 7
SP - 27
EP - 38
JO - The Lancet. Oncology
JF - The Lancet. Oncology
IS - 1
ER -
