Cytokine polymorphisms in Th1/Th2 pathway genes, body mass index, and risk of non-Hodgkin lymphoma

January 14, 2011

BlankBlood, 13 January 2011, Vol. 117, No. 2, pp. 585-590.

Prepublished online as a Blood First Edition Paper on October 15, 2010; DOI

10.1182/blood-2010-07-295097.

Cytokine polymorphisms in Th1/Th2 pathway genes, body mass index, and risk of

non-Hodgkin lymphoma

Yingtai Chen1,2, Tongzhang Zheng2, Qing Lan3, Francine Foss4, Kim2,

Xuezhong Chen5, Min Dai6, Yumin Li1, Theodore Holford2, Leaderer2,

Boyle7, J. Chanock3,8, iel Rothman3, and Yawei Zhang2

1 The Second Hospital of Lanzhou University, Lanzhou, China; 2 Yale University

School of Public Health, New Haven, CT; 3 Division of Cancer Epidemiology and

Genetics, National Cancer Institute, National Institutes of Health, Department

of Health and Human Services, Rockville, MD; 4 Yale University School of

Medicine, New Haven, CT; 5 Gansu Provincial Tumor Hospital, Gansu Provincial

Academy of Medical Sciences, Lanzhou, China; 6 Cancer Institute/Hospital,

Chinese Academy of Medical Sciences, Beijing, China; 7 International Preventive

Research Institute, Lyon, France; and 8 Core Genotyping Facility, Advanced

Technology Center, National Cancer Institute, National Institutes of Health,

Department of Health and Human Services, Gaithersburg, MD

We conducted a population-based, case-control study in Connecticut women to test

the hypothesis that genetic variations in Th1 and Th2 cytokine genes modify the

relationship between body mass index (BMI) and risk of non-Hodgkin lymphoma

(NHL). Compared with those with BMI less than 25 kg/m2, women with BMI more than

or equal to 25 kg/m2 had 50% to 90% increased risk of NHL among women who

carried IFNGR2 (rs9808753) AA, IL5 (rs2069812) CT/TT, IL7R (rs1494555) AA, and

TNF (rs1799724) CC genotypes, but no increased risk among women with IFNGR2

AG/GG, IL5 CC, IL7R AG/GG, and TNF CT/TT genotypes. A significant interaction

with BMI was only observed for IFNGR2 (rs9808753 Pforinteraction = .034) and

IL7R (rs1494555 Pforinteraction = .016) for NHL overall; IL7R (rs1494555

Pforinteraction = .016) and TNF (1799724 Pforinteraction = .031) for B-cell

lymphoma; and IL5 (rs2069812 Pforinteraction = .034) for T-cell lymphoma. After

stratification by common B-cell lymphoma subtypes, a significant interaction was

observed for IFNGR2 (rs9808753 Pforinteraction = .006), IL13 (rs20541

Pforinteraction = .019), and IL7R (rs1494555 Pforinteraction = .012) for

marginal zone B-cell lymphoma; IL7R (rs1494555 Pforinteraction = .017) for small

lymphocytic lymphoma/chronic lymphocytic leukemia; and IL12A (rs568408

Pforinteraction = .013) and TNF (1799724 Pforinteraction = .04) for follicular

lymphoma. The results suggest that common genetic variation in Th1/Th2 pathway

genes may modify the association between BMI and NHL risk.

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