Non-Hodgkin lymphoma, body mass index and cytokine polymorphisms: a pooled analysis from the InterLymph consortium

Eleanor Kane; Christine F. Skibola; Paige M. Bracci; James R. Cerhan; Laura Costas; Karin Ekström Smedby; Elizabeth A. Holly; Marc Maynadie; Anne J. Novak; Tracy J. Lightfoot; Stephen M Ansell; Alex G Smith; Mark Liebow; Mads Melbye; Lindsay M. Morton; Silvia de Sanjose; Susan L. Slager; Sophia S Wang; Yawei Zhang; Tongzhang Zheng; Eve Roman

doi:10.1158/1055-9965.EPI-14-1355

Non-Hodgkin lymphoma, body mass index and cytokine polymorphisms: a pooled analysis from the InterLymph consortium

Eleanor Kane, Christine F. Skibola, Paige M. Bracci, James R. Cerhan, Laura Costas, Karin Ekström Smedby, Elizabeth A. Holly, Marc Maynadie, Anne J. Novak, Tracy J. Lightfoot, Stephen M Ansell, Alex G Smith, Mark Liebow, Mads Melbye, Lindsay M. Morton, Silvia de Sanjose, Susan L. Slager, Sophia S Wang, Yawei Zhang, Tongzhang ZhengEve Roman

Health Sciences

Research output: Contribution to journal › Article › peer-review

Abstract

BACKGROUND: Excess adiposity has been associated with lymphomagenesis, possibly mediated by increased cytokine production causing a chronic inflammatory state. The relationship between obesity, cytokine polymorphisms and selected mature B-cell neoplasms is reported.

METHOD: Data on 4979 cases and 4752 controls from nine American/European studies from the InterLymph consortium (1988-2008) were pooled. For diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL), joint associations of body mass index (from self-reported height and weight) and 12 polymorphisms in cytokines IL1A (rs1800587), IL1B (rs16944, rs1143627), IL1RN (rs454078), IL2 (rs2069762), IL6 (rs1800795, rs1800797), IL10 (rs1800890, rs1800896), TNF (rs1800629), LTA (rs909253), and CARD15 (rs2066847) were investigated using unconditional logistic regression. BMI-polymorphism interaction effects were estimated using the relative excess risk due to interaction (RERI).

RESULTS: Obesity (BMI≥30kg m-2) was associated with DLBCL risk (OR=1.33, 95%CI 1.02-1.73), as was TNF-308GA+AA (OR=1.24, 95%CI 1.07-1.44). Together, being obese and TNF-308GA+AA increased DLBCL risk almost two-fold relative to those of normal weight and TNF-308GG (OR=1.93 95%CI 1.27-2.94), with a RERI of 0.41 (95%CI -0.05,0.84, P(interaction)=0.13). For FL and CLL/SLL, no associations with obesity or TNF-308GA+AA, either singly or jointly, were observed. No evidence of interactions between obesity and the other polymorphisms were detected.

CONCLUSIONS: Our results suggest that cytokine polymorphisms do not generally interact with BMI to increase lymphoma risk but obesity and TNF-308GA+AA may interact to increase DLBCL risk.

IMPACT: Studies using better measures of adiposity are needed to further investigate the interactions between obesity and TNF-308G>A in the pathogenesis of lymphoma.

Original language	English
Pages (from-to)	1251-1256
Number of pages	6
Journal	Cancer Epidemiology Biomarkers & Prevention
Volume	14
Issue number	5
Early online date	11 May 2015
DOIs	https://doi.org/10.1158/1055-9965.EPI-14-1355
Publication status	Published - May 2015

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Kane, E., Skibola, C. F., Bracci, P. M., Cerhan, J. R., Costas, L., Ekström Smedby, K., Holly, E. A., Maynadie, M., Novak, A. J., Lightfoot, T. J., Ansell, S. M., Smith, A. G., Liebow, M., Melbye, M., Morton, L. M., de Sanjose, S., Slager, S. L., Wang, S. S., Zhang, Y., ... Roman, E. (2015). Non-Hodgkin lymphoma, body mass index and cytokine polymorphisms: a pooled analysis from the InterLymph consortium. Cancer Epidemiology Biomarkers & Prevention, 14(5), 1251-1256. https://doi.org/10.1158/1055-9965.EPI-14-1355

@article{a87d09d5b96e484b8ae205ec99f9263b,

title = "Non-Hodgkin lymphoma, body mass index and cytokine polymorphisms: a pooled analysis from the InterLymph consortium",

abstract = "BACKGROUND: Excess adiposity has been associated with lymphomagenesis, possibly mediated by increased cytokine production causing a chronic inflammatory state. The relationship between obesity, cytokine polymorphisms and selected mature B-cell neoplasms is reported.METHOD: Data on 4979 cases and 4752 controls from nine American/European studies from the InterLymph consortium (1988-2008) were pooled. For diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL), joint associations of body mass index (from self-reported height and weight) and 12 polymorphisms in cytokines IL1A (rs1800587), IL1B (rs16944, rs1143627), IL1RN (rs454078), IL2 (rs2069762), IL6 (rs1800795, rs1800797), IL10 (rs1800890, rs1800896), TNF (rs1800629), LTA (rs909253), and CARD15 (rs2066847) were investigated using unconditional logistic regression. BMI-polymorphism interaction effects were estimated using the relative excess risk due to interaction (RERI).RESULTS: Obesity (BMI≥30kg m-2) was associated with DLBCL risk (OR=1.33, 95%CI 1.02-1.73), as was TNF-308GA+AA (OR=1.24, 95%CI 1.07-1.44). Together, being obese and TNF-308GA+AA increased DLBCL risk almost two-fold relative to those of normal weight and TNF-308GG (OR=1.93 95%CI 1.27-2.94), with a RERI of 0.41 (95%CI -0.05,0.84, P(interaction)=0.13). For FL and CLL/SLL, no associations with obesity or TNF-308GA+AA, either singly or jointly, were observed. No evidence of interactions between obesity and the other polymorphisms were detected.CONCLUSIONS: Our results suggest that cytokine polymorphisms do not generally interact with BMI to increase lymphoma risk but obesity and TNF-308GA+AA may interact to increase DLBCL risk.IMPACT: Studies using better measures of adiposity are needed to further investigate the interactions between obesity and TNF-308G>A in the pathogenesis of lymphoma.",

author = "Eleanor Kane and Skibola, {Christine F.} and Bracci, {Paige M.} and Cerhan, {James R.} and Laura Costas and {Ekstr{\"o}m Smedby}, Karin and Holly, {Elizabeth A.} and Marc Maynadie and Novak, {Anne J.} and Lightfoot, {Tracy J.} and Ansell, {Stephen M} and Smith, {Alex G} and Mark Liebow and Mads Melbye and Morton, {Lindsay M.} and {de Sanjose}, Silvia and Slager, {Susan L.} and Wang, {Sophia S} and Yawei Zhang and Tongzhang Zheng and Eve Roman",

note = "Copyright {\textcopyright} 2015, American Association for Cancer Research.",

year = "2015",

month = may,

doi = "10.1158/1055-9965.EPI-14-1355",

language = "English",

volume = "14",

pages = "1251--1256",

journal = "Cancer Epidemiology Biomarkers & Prevention",

issn = "1055-9965",

publisher = "American Association for Cancer Research Inc.",

number = "5",

}

Kane, E, Skibola, CF, Bracci, PM, Cerhan, JR, Costas, L, Ekström Smedby, K, Holly, EA, Maynadie, M, Novak, AJ, Lightfoot, TJ, Ansell, SM, Smith, AG, Liebow, M, Melbye, M, Morton, LM, de Sanjose, S, Slager, SL, Wang, SS, Zhang, Y, Zheng, T & Roman, E 2015, 'Non-Hodgkin lymphoma, body mass index and cytokine polymorphisms: a pooled analysis from the InterLymph consortium', Cancer Epidemiology Biomarkers & Prevention, vol. 14, no. 5, pp. 1251-1256. https://doi.org/10.1158/1055-9965.EPI-14-1355

TY - JOUR

T1 - Non-Hodgkin lymphoma, body mass index and cytokine polymorphisms

T2 - a pooled analysis from the InterLymph consortium

AU - Kane, Eleanor

AU - Skibola, Christine F.

AU - Bracci, Paige M.

AU - Cerhan, James R.

AU - Costas, Laura

AU - Ekström Smedby, Karin

AU - Holly, Elizabeth A.

AU - Maynadie, Marc

AU - Novak, Anne J.

AU - Lightfoot, Tracy J.

AU - Ansell, Stephen M

AU - Smith, Alex G

AU - Liebow, Mark

AU - Melbye, Mads

AU - Morton, Lindsay M.

AU - de Sanjose, Silvia

AU - Slager, Susan L.

AU - Wang, Sophia S

AU - Zhang, Yawei

AU - Zheng, Tongzhang

AU - Roman, Eve

PY - 2015/5

Y1 - 2015/5

N2 - BACKGROUND: Excess adiposity has been associated with lymphomagenesis, possibly mediated by increased cytokine production causing a chronic inflammatory state. The relationship between obesity, cytokine polymorphisms and selected mature B-cell neoplasms is reported.METHOD: Data on 4979 cases and 4752 controls from nine American/European studies from the InterLymph consortium (1988-2008) were pooled. For diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL), joint associations of body mass index (from self-reported height and weight) and 12 polymorphisms in cytokines IL1A (rs1800587), IL1B (rs16944, rs1143627), IL1RN (rs454078), IL2 (rs2069762), IL6 (rs1800795, rs1800797), IL10 (rs1800890, rs1800896), TNF (rs1800629), LTA (rs909253), and CARD15 (rs2066847) were investigated using unconditional logistic regression. BMI-polymorphism interaction effects were estimated using the relative excess risk due to interaction (RERI).RESULTS: Obesity (BMI≥30kg m-2) was associated with DLBCL risk (OR=1.33, 95%CI 1.02-1.73), as was TNF-308GA+AA (OR=1.24, 95%CI 1.07-1.44). Together, being obese and TNF-308GA+AA increased DLBCL risk almost two-fold relative to those of normal weight and TNF-308GG (OR=1.93 95%CI 1.27-2.94), with a RERI of 0.41 (95%CI -0.05,0.84, P(interaction)=0.13). For FL and CLL/SLL, no associations with obesity or TNF-308GA+AA, either singly or jointly, were observed. No evidence of interactions between obesity and the other polymorphisms were detected.CONCLUSIONS: Our results suggest that cytokine polymorphisms do not generally interact with BMI to increase lymphoma risk but obesity and TNF-308GA+AA may interact to increase DLBCL risk.IMPACT: Studies using better measures of adiposity are needed to further investigate the interactions between obesity and TNF-308G>A in the pathogenesis of lymphoma.

AB - BACKGROUND: Excess adiposity has been associated with lymphomagenesis, possibly mediated by increased cytokine production causing a chronic inflammatory state. The relationship between obesity, cytokine polymorphisms and selected mature B-cell neoplasms is reported.METHOD: Data on 4979 cases and 4752 controls from nine American/European studies from the InterLymph consortium (1988-2008) were pooled. For diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL), joint associations of body mass index (from self-reported height and weight) and 12 polymorphisms in cytokines IL1A (rs1800587), IL1B (rs16944, rs1143627), IL1RN (rs454078), IL2 (rs2069762), IL6 (rs1800795, rs1800797), IL10 (rs1800890, rs1800896), TNF (rs1800629), LTA (rs909253), and CARD15 (rs2066847) were investigated using unconditional logistic regression. BMI-polymorphism interaction effects were estimated using the relative excess risk due to interaction (RERI).RESULTS: Obesity (BMI≥30kg m-2) was associated with DLBCL risk (OR=1.33, 95%CI 1.02-1.73), as was TNF-308GA+AA (OR=1.24, 95%CI 1.07-1.44). Together, being obese and TNF-308GA+AA increased DLBCL risk almost two-fold relative to those of normal weight and TNF-308GG (OR=1.93 95%CI 1.27-2.94), with a RERI of 0.41 (95%CI -0.05,0.84, P(interaction)=0.13). For FL and CLL/SLL, no associations with obesity or TNF-308GA+AA, either singly or jointly, were observed. No evidence of interactions between obesity and the other polymorphisms were detected.CONCLUSIONS: Our results suggest that cytokine polymorphisms do not generally interact with BMI to increase lymphoma risk but obesity and TNF-308GA+AA may interact to increase DLBCL risk.IMPACT: Studies using better measures of adiposity are needed to further investigate the interactions between obesity and TNF-308G>A in the pathogenesis of lymphoma.

U2 - 10.1158/1055-9965.EPI-14-1355

DO - 10.1158/1055-9965.EPI-14-1355

M3 - Article

C2 - 25962811

SN - 1055-9965

VL - 14

SP - 1251

EP - 1256

JO - Cancer Epidemiology Biomarkers & Prevention

JF - Cancer Epidemiology Biomarkers & Prevention

IS - 5

ER -