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, Xavier F.
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
N1 - Funding Information:
We thank Randy D Gascoyne, Joseph M Connors, and Stephen Leach from the British Columbia study; Graham Law and Alexandra Smith from the UK study; Giorgio Broccia, Emanuele Angelucci, Attilio Gabbas, and Giovannino Massarelli from the EPILYMPH—Italy study; Rebeca Font, Yolanda Benavente, Elisabeth Guino, Alberto Fernandez de Sevilla, Tomas Alvaro, Mercedes Garcia, and Vicens Romagosa from the EPILYMPH—Spain study; Ina Koegel and Evelin Deeg from the EPILYMPH—Germany study; Brian Chiu from the InterLymph genotyping working group; and Nilanjan Chatterjee, Geoffrey Tobias, Lindsay Morton, Robert N Hoover, and Joseph F Fraumeni Jr, from the US National Cancer Institute (NCI). This project was supported by a European Commission grant to EPILYMPH (Grant number QLK4-CT-2000-00422); US National Institutes of Health (NIH) grants CA104862 (M T Smith, principal investigator) and CA45614, CA89745 and CA87014 (E A Holly, principal investigator), University of California San Francisco; Federal funds from the NCI, NIH, under contract NO1-CO-12400; Fondazione Cariverona (2004, A Scarpa; 2005, PS Moore), and Compagnia di S Paolo—Programma Oncologia (P Cocco), EPILYMPH—Italy; German José Carreras Leukemia Foundation DJCLS-R04/08 (A Nieters, principal investigator) and Federal Office for Radiation Protection (StSch4261 and StSch4420) (N Becker, principal investigator), EPILYMPH—Germany; FISS grant PI040091 (S De Sanjose, principal investigator), RCESP 03/09, and FISS grant PI041467 (R Bosch, principal investigator.), EPILYMPH—Spain; National Cancer Institute of Canada, the Chan Sisters Foundation, and the Canadian Institutes for Health Research, British Columbia; Leukaemia Research, UK; and the Intramural Research Program of the US NIH, NCI, NCI-SEER.
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.
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U2 - 10.1016/S1470-2045(05)70434-4
DO - 10.1016/S1470-2045(05)70434-4
M3 - Article
C2 - 16389181
AN - SCOPUS:29744459902
SN - 1470-2045
VL - 7
SP - 27
EP - 38
JO - Lancet Oncology
JF - Lancet Oncology
IS - 1
ER -