Cancer Causes & Control

, Volume 24, Issue 10, pp 1875–1884 | Cite as

Role of one-carbon metabolizing pathway genes and gene–nutrient interaction in the risk of non-Hodgkin lymphoma

  • Qian Li
  • Qing Lan
  • Yawei Zhang
  • Bryan A. Bassig
  • Theodore R. Holford
  • Brian Leaderer
  • Peter Boyle
  • Yong Zhu
  • Qin Qin
  • Stephen Chanock
  • Nathaniel Rothman
  • Tongzhang ZhengEmail author
Original Paper



Genetic polymorphisms in one-carbon metabolizing pathway genes have been associated with risk of malignant lymphoma. However, the results have been inconsistent. The objectives of this study were to examine the potential relationship between genenutrient interactions and the risk of non-Hodgkin lymphoma (NHL).


We examined 25 polymorphisms in 16 one-carbon metabolism genes for their main effect and genenutrient interactions in relation to NHL risk among 518 incident cases and 597 population-based controls of Connecticut women enrolled between 1996 and 2000.


A significantly reduced risk of NHL was associated with the homozygous TT genotype in CBS (rs234706, Ex9+33C>T) (OR = 0.51, 95 % CI 0.31–0.84), the homozygous CC genotype in MBD2 (rs603097, −2176C>T) (OR = 0.37, 95 % CI 0.17–0.79), the heterozygote AG genotype in FTHFD (rs1127717, Ex21+31A>G) (OR = 0.73, 95 % CI 0.55–0.98), and a borderline significantly reduced risk of NHL was observed for the homozygous CC genotype in MTRR (rs161870, Ex5+136T>C) (OR = 0.23, 95 % CI 0.05–1.04). The reduced risk of NHL associated with these genotypes was predominately in those with higher dietary vitamin B6 and methionine intakes, as well as with higher dietary folate intake although results were less stable. A borderline significantly increased risk of NHL was also observed for CBS (rs1801181, Ex13+41C>T), FTHFD (rs2305230, Ex10−40G>T), SHMT1 (rs1979277, Ex12+138C>T), and SHMT1 (rs1979276, Ex12+236T>C), and these associations appeared to be contingent on dietary nutrient intakes.


Our results suggest that variation in several one-carbon metabolizing pathway genes may influence the risk of NHL through genenutrient interactions involving dietary nutrient intakes.


Dietary nutrients Folate One-carbon metabolizing genes Non-Hodgkin lymphoma Cancer 



This work was supported by the National Institutes of Health (Grant CA62006), the Intramural Research Program of the National Institutes of Health, National Cancer Institute, and the National Institutes of Health Fogarty (training Grants D43TW008323-01 and D43TW007864-01).

Conflict of interest

None declared.

Supplementary material

10552_2013_264_MOESM1_ESM.docx (88 kb)
Supplementary material 1 (DOCX 88 kb)


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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Qian Li
    • 1
    • 2
  • Qing Lan
    • 3
  • Yawei Zhang
    • 1
  • Bryan A. Bassig
    • 1
  • Theodore R. Holford
    • 1
  • Brian Leaderer
    • 1
  • Peter Boyle
    • 4
  • Yong Zhu
    • 1
  • Qin Qin
    • 5
  • Stephen Chanock
    • 3
  • Nathaniel Rothman
    • 3
  • Tongzhang Zheng
    • 1
    Email author
  1. 1.Department of Environmental Health SciencesYale School of Public HealthNew HavenUSA
  2. 2.Department of Preventive MedicineIcahn School of Medicine at Mount SinaiNew YorkUSA
  3. 3.Division of Cancer Epidemiology and Genetics, National Cancer InstituteNIH, DHHSBethesdaUSA
  4. 4.International Prevention Research Institute (IPRI)LyonFrance
  5. 5.Wise Laboratory of Environmental and Genetic ToxicologyUniversity of Southern MainePortlandUSA

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