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Polymorphisms in DNA repair and one-carbon metabolism genes and overall survival in diffuse large B-cell lymphoma and follicular lymphoma

Leukemia volume 23, pages 596–602 (2009)Cite this article

Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) are the two most commonly diagnosed subtypes of non-Hodgkin's lymphoma (NHL) in the United States.1 Both diseases show variable progression, and identifying prognostic markers applicable in a clinical setting could greatly improve patient management. Established adverse prognostic factors in DLBCL as delineated in the International Prognostic Factor Index (IPI) include older age, higher stage, poor performance score, extranodal involvement and above normal lactate dehydrogenase. For FL, adverse prognostic factors are combined in the Follicular Lymphoma International Prognostic Index and include older age, higher stage, lower hemoglobin level, more nodal areas and above normal lactate dehydrogenase. As both IPI and Follicular Lymphoma International Prognostic Index predict risk incompletely, it is thought that molecular characteristics of the tumor and its microenvironment may improve predicting DLBCL and FL survival. Notably, recent gene expression studies suggest a molecular profile of DLBCL with poorer survival.2 New prognostic markers for FL have also been suggested,3 but none have yet been translated to the clinical setting. Evaluating host germline genetic variability offers another promising approach for refining prognosis of DLBCL and FL.

DNA repair and one-carbon metabolism pathways have important functions in maintaining DNA and chromosomal integrity. Briefly, chromosomal translocations, a hallmark of NHL, result from V(D)J recombination or persistent unrepaired DNA double-strand breakage. The ability of a host to repair DNA damage reflects mutations and variations in a large suite of genes that affect non-homologous end joining, homologous recombinational repair, nucleotide-excision repair, base-excision repair and direct damage reversal. DNA damage can also result indirectly when one-carbon metabolism is disrupted from nutrient deficiency (for example, folate and methionine) or from genetic variation in one-carbon metabolism genes. Disruptions within one-carbon metabolism have been linked to insufficient DNA synthesis/repair and subsequent aberrant gene expression.

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Acknowledgements

We thank Peter Hui and Cristine Allmer for data management, and Laura Huennekens for secretarial support. We also thank Drs Qing Lan and Deirdre Hill for their scientific input for selection of one-carbon metabolism and DNA repair genes, respectively, as hypothesized for NHL etiology. This work was supported by National Cancer Institute grants R01-CA96704 and P50-CA97274; the NCI Intramural Program; SEER contracts N01-PC-67010, N01-PC-67008, N01-PC-67009, N01-PC-65064 and N02-PC-71105.

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Authors and Affiliations

  1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA

    S S Wang, L M Morton, N Rothman, S J Chanock & P Hartge

  2. Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA

    M J Maurer, T M Habermann & J R Cerhan

  3. Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    S Davis

  4. Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA

    W Cozen

  5. Department of Epidemiology, University of Iowa, Iowa City, IA, USA

    C F Lynch

  6. Department of Family Medicine and Public Health Sciences and Karmanos Cancer Institute, Detroit, MI, USA

    R K Severson

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Correspondence to S S Wang.

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Wang, S., Maurer, M., Morton, L. et al. Polymorphisms in DNA repair and one-carbon metabolism genes and overall survival in diffuse large B-cell lymphoma and follicular lymphoma. Leukemia 23, 596–602 (2009). https://doi.org/10.1038/leu.2008.240

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