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

  1. Author:
    Lee, K. M.
    Lan, Q.
    Kricker, A.
    Purdue, M. P.
    Grulich, A. E.
    Vajdic, C. M.
    Turner, J.
    Whitby, D.
    Kang, D.
    Chanock, S.
    Rothman, N.
    Armstrong, B. K.

  2. Author Address

    Natl Canc Inst, NIH, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch,DHHS, Bethesda, MD 20892 USA. Univ Sydney, Sch Publ Hlth, Sydney, NSW, Australia. Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW, Australia. St Vincents Hosp, Sydney, NSW 2010, Australia. NCI, Frederick, MD 21701 USA. Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea. NCI, NIH, Ctr Canc Res, Ctr Adv Technol,Div Canc Epidemiol & Genet Pediat, Bethesda, MD USA.;Lee, KM, Natl Canc Inst, NIH, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch,DHHS, 6120 Executive Blvd EPS 8118, Bethesda, MD 20892 USA.;leekyou@mail.nih.gov
    1. Year: 2007
    2. Date: Dec
  2. Journal: Human Genetics
    1. 122
    2. 5
    3. Pages: 525-533
  4. Type of Article: Article
  5. ISSN: 0340-6717
  1. 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; P = 0.008), but not for follicular lymphoma (FL; P = 0.27) or all NHL (P = 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 TYMS Ex8+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 FTHFD Ex21+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+79 T allele and increased NHL risk (additive model, P = 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.

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External Sources

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  2. DOI: 10.1007/s00439-007-0431-2
  3. View record in Web of Science®
  4. WOS: 000251143900012

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