Human Genetics

, Volume 122, Issue 5, pp 525–533

One-carbon metabolism gene polymorphisms and risk of non-Hodgkin lymphoma in Australia

  • Kyoung-Mu Lee
  • Qing Lan
  • Anne Kricker
  • Mark P. Purdue
  • Andrew E. Grulich
  • Claire M. Vajdic
  • Jennifer Turner
  • Denise Whitby
  • Daehee Kang
  • Stephen Chanock
  • Nathaniel Rothman
  • Bruce K. Armstrong
Original Investigation

DOI: 10.1007/s00439-007-0431-2

Cite this article as:
Lee, KM., Lan, Q., Kricker, A. et al. Hum Genet (2007) 122: 525. doi:10.1007/s00439-007-0431-2

Abstract

Dysregulation of the one-carbon metabolic pathway, which controls nucleotide synthesis and DNA methylation, may promote lymphomagenesis. We evaluated the association between polymorphisms in one-carbon metabolism genes and risk of non-Hodgkin lymphoma (NHL) in a population-based case-control study in Australia. Cases (n = 561) and controls (n = 506) were genotyped for 14 selected single-nucleotide polymorphisms in 10 genes (CBS, FPGS, FTHFD, MTHFR, MTHFS, MTR, SHMT1, SLC19A1, TCN1, and TYMS). We also conducted a meta-analysis of all studies of Caucasian populations investigating the association between MTHFR Ex5+79C > T (a.k.a., 677C>T) and NHL risk. A global test of 13 genotypes was statistically significant for diffuse large B-cell lymphoma (DLBCL; = 0.008), but not for follicular lymphoma (FL; = 0.27) or all NHL (= 0.17). The T allele at MTHFR Ex5+79 was marginally significantly associated with all NHL (OR = 1.25, 95% CI = 0.98–1.59) and DLBCL (1.36, 0.96–1.93). The T allele at TYMSEx8+157 was associated with a reduced risk of FL (0.64, 0.46–0.91). An elevated risk of NHL was also observed among carriers of the G allele at FTHFDEx21+31 (all NHL, 1.31, 1.02–1.69; DLBCL, 1.50, 1.05–2.14). A meta-analysis of 11 studies conducted in Caucasian populations of European origin (4,121 cases and 5,358 controls) supported an association between the MTHFR Ex5+79T allele and increased NHL risk (additive model, = 0.01). In conclusion, the results of this study suggest that genetic polymorphisms of one-carbon metabolism genes such as MTHFR and TYMS may influence susceptibility to NHL.

Supplementary material

439_2007_431_MOESM1_ESM.doc (288 kb)
Supplementary Table I Main effect of SNPs in one-carbon metabolism genes on NHL risk in Australia: SNPs for which little indication of a statistically significant association with NHL (DOC 288 kb)

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Kyoung-Mu Lee
    • 1
  • Qing Lan
    • 1
  • Anne Kricker
    • 2
  • Mark P. Purdue
    • 1
  • Andrew E. Grulich
    • 3
  • Claire M. Vajdic
    • 3
  • Jennifer Turner
    • 4
  • Denise Whitby
    • 5
  • Daehee Kang
    • 6
  • Stephen Chanock
    • 7
  • Nathaniel Rothman
    • 1
  • Bruce K. Armstrong
    • 2
  1. 1.Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and GeneticsNational Cancer Institute, NIH, DHHSBethesdaUSA
  2. 2.School of Public HealthThe University of SydneySydneyAustralia
  3. 3.National Centre for HIV Epidemiology and Clinical ResearchSydneyAustralia
  4. 4.St. Vincent’s HospitalSydneyAustralia
  5. 5.NCI-FrederickFrederickUSA
  6. 6.Department of Preventive MedicineSeoul National University College of MedicineSeoulSouth Korea
  7. 7.Core Genotyping Facility, Advanced Technology Center, Division of Cancer Epidemiology and Genetics and Pediatric Oncology BranchCenter for Cancer Research, NCI, NIH, DHHSBethesdaUSA