Tumor Biology

, Volume 36, Issue 3, pp 1819–1834 | Cite as

Genetic polymorphisms in the one-carbon metabolism pathway genes and susceptibility to non-Hodgkin lymphoma

  • Sujatha Suthandiram
  • Gin-Gin Gan
  • Shamsul Mohd Zain
  • Ping-Chong Bee
  • Lay-Hoong Lian
  • Kian-Meng Chang
  • Tee-Chuan Ong
  • Zahurin Mohamed
Research Article


Corroborating evidence related to the role of aberrations on one-carbon metabolism (OCM) genes has been inconsistent. We evaluated the association between polymorphisms in 12 single nucleotide polymorphisms (SNPs) in 8 OCM genes (CBS, FPGS, FTHFD, MTRR, SHMT1, SLC19A1, TCN1, and TYMS), and non-Hodgkin lymphoma (NHL) risk in a multi-ethnic population which includes Malay, Chinese and Indian ethnic subgroups. Cases (N = 372) and controls (N = 722) were genotyped using the Sequenom MassARRAY platform. Our results of the pooled subjects showed a significantly enhanced NHL risk for CBS Ex9 + 33C > T (T versus C: OR 1.55, 95 % CI 1.22–1.96, P = 0.0003), CBS Ex18-319G > A (A versus G: OR 1.15, 95 % CI 1.14–1.83; P = 0.002), SHMT1 Ex12 + 236 T > C (T versus C: OR 1.44, 95 % CI 1.15–1.81, P = 0.002), and TYMS Ex8 + 157C > T (T versus C: OR 1.29, 95 % CI 1.06–1.57, P = 0.01). Haplotype analysis for CBS SNPs showed a significantly decreased risk of NHL in subjects with haplotype CG (OR 0.69, 95 % CI 0.56–0.86, P = <0.001). The GG haplotype for the FTHFD SNPs showed a significant increased risk of NHL (OR 1.40, 95 % CI 1.12–1.76, P = 0.002). For the TYMS gene, haplotype CAT at TYMS (OR 0.67, 95 % CI 0.49–0.90, P = 0.007) was associated with decreased risk of NHL, while haplotype TAC (OR 1.29, 95 % CI 1.05–1.58, P = 0.01) was found to confer increased risk of NHL. Our study suggests that variation in several OCM genes (CBS, FTHFD, SHMT1, TCN1, and TYMS) may influence susceptibility to NHL.


Genetic polymorphisms One-carbon metabolism pathway Non-Hodgkin lymphoma 



The authors would like to thank the Director of Health Malaysia for permission to publish this paper. The authors gratefully acknowledge the study subjects for their participation in this study and to the staff of UMMC and Ampang Hospital for their assistance in subject recruitment. This study was supported by the HIR MOHE grant E000025-20001, University Malaya Research Grant (UMRG; RG300/11HTM), University Malaya IPPP grant (PV072/2011B) and University Malaya IPPP grant (PS190/2010B).

Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Sujatha Suthandiram
    • 1
  • Gin-Gin Gan
    • 2
  • Shamsul Mohd Zain
    • 1
  • Ping-Chong Bee
    • 2
  • Lay-Hoong Lian
    • 3
  • Kian-Meng Chang
    • 4
  • Tee-Chuan Ong
    • 4
  • Zahurin Mohamed
    • 1
  1. 1.The Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of MedicineUniversity of MalayaKuala LumpurMalaysia
  2. 2.Department of MedicineUniversity of MalayaKuala LumpurMalaysia
  3. 3.Department of Molecular Medicine, Faculty of MedicineUniversity of MalayaKuala LumpurMalaysia
  4. 4.Department of HematologyAmpang HospitalKuala LumpurMalaysia

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