The Lymphoma and Leukaemia Working Group

Non-Hodgkin lymphomas (NHL) have shown increasing incidence over the past decades in several countries. They are the 10th most common cause of cancer death in the world. They constitute a heterogeneous group that predominantly arises from B-cell lymphocytes. The etiology of NHL remains mostly unknown, and only a few risk factors have been clearly established. Among them, immune dysregulation is believed to play a major role.

The Working Group has been active in analysing exposure data on NHL and particularly in measuring a number of biomarkers. Overall, the group has identified and confirmed more than 1900 subjects with a malignant lymphoma (newly diagnosed after cohort inception) in EPIC, including more than 1700 with B-cell NHL.

Currently available biomarkers and genetic data in EPIC (obtained through a case—control approach nested in the cohort) include:

  • (14;18) translocations in follicular lymphomas
  • Mitochondrial DNA copy number variation (mtDNA CNV) and telomere length in white blood cells
  • Omic biomarkers (epigenome-wide association study, transcriptomics, proteomics, metabolomics) in a subset of the EnviroGenoMarkers (EGM) investigation
  • Persistent organic pollutants (POPs) in a subset (EGM investigation)
  • Genome-wide association studies (GWAS) (phase I and replication) conducted within the NCI NHL Consortium
  • IgE and IGF-1, IGF-2
  • Seropositivity to anti-HCV, anti-HBc and HBsAg
  • Soluble B-cell activation markers

Leukemia is a cancer of the body's blood-forming tissues, including the bone marrow and the lymphatic system. Some forms of leukemia are more common in children. Other forms of leukemia occur mostly in adults. The Working Group has recently expanded its work on leukemia especially as some leukemias are now included in the definition of lymphoma.

Currently available biomarkers and genetic data in EPIC (obtained through a case–control approach nested in the cohort) include:

  • Targeted sequencing of AML-associated genes

Selected publications:

  1. Saberi Hosnijeh F et al. Occupation and risk of lymphoid and myeloid leukaemia in the European Prospective Investigation into Cancer and Nutrition (EPIC). Occup Environ Med. 2013 Jul;70(7):464-70. doi: 10.1136/oemed-2012-101135. Epub 2013 Apr 10. PMID: 23576671
  2. Abelson S et al. Prediction of acute myeloid leukaemia risk in healthy individuals. Nature. 2018 Jul;559(7714):400-404. doi: 10.1038/s41586-018-0317-6. Epub 2018 Jul 9. PMID: 29988082 Free PMC article.
  3. Solans M et al. Inflammatory potential of diet and risk of lymphoma in the European Prospective Investigation into Cancer and Nutrition. Eur J Nutr. 2020 Mar;59(2):813-823. doi: 10.1007/s00394-019-01947-0. Epub 2019 Mar 22. PMID: 30903361
  4. Kelly RS et al. Prediagnostic plasma concentrations of organochlorines and risk of B-cell non-Hodgkin lymphoma in envirogenomarkers: a nested case-control study. Environ Health. 2017 Feb 16;16(1):9. doi: 10.1186/s12940-017-0214-8. PMID: 28202064 Free PMC article.
  5. Perez-Cornago A et al. Prediagnostic circulating concentrations of plasma insulin-like growth factor-I and risk of lymphoma in the European Prospective Investigation into Cancer and Nutrition. Int J Cancer. 2017 Mar 1;140(5):1111-1118. doi: 10.1002/ijc.30528. Epub 2016 Dec 27. PMID: 27870006 Free PMC article.
  6. Lu Y et al. Comparison of abdominal adiposity and overall obesity in relation to risk of small intestinal cancer in a European Prospective Cohort. Cancer Causes Control. 2016 Jul;27(7):919-27. doi: 10.1007/s10552-016-0772-z. Epub 2016 Jun 13. PMID: 27294726 Free PMC article.
  7. Kleinstern G et al. Inherited variants at 3q13.33 and 3p24.1 are associated with risk of diffuse large B-cell lymphoma and implicate immune pathways. Hum Mol Genet. 2020 Jan 1;29(1):70-79. doi: 10.1093/hmg/ddz228. PMID: 31600786
  8. McMaster ML et al. Two high-risk susceptibility loci at 6p25.3 and 14q32.13 for Waldenström macroglobulinemia. Nat Commun. 2018 Oct 10;9(1):4182. doi: 10.1038/s41467-018-06541-2. PMID: 30305637 Free PMC article.
  9. Vermeulen R et al. Pre-diagnostic blood immune markers, incidence and progression of B-cell lymphoma and multiple myeloma: Univariate and functionally informed multivariate analyses. Int J Cancer. 2018 Sep 15;143(6):1335-1347. doi: 10.1002/ijc.31536. Epub 2018 Apr 26. PMID: 29667176 Free PMC article.
  10. Chadeau-Hyam M et al. on behalf of the EnviroGenoMarkers project consortium. Pre-diagnostic transcriptomic markers of chronic lymphocytic leukemia reveal perturbations 10 years before diagnosis. Ann Oncol. 2014 Feb 20. [Epub ahead of print] PMID: 24558024
  11. Łuczyńska A et al. Plasma 25-hydroxyvitamin D concentration and lymphoma risk: results of the European Prospective Investigation into Cancer and Nutrition. Am J Clin Nutr. 2013 Sep;98(3):827-38. doi: 10.3945/ajcn.112.054676. Epub 2013 Jul 24. PMID: 23885049
  12. Berndt SI et al. Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia. Nat Genet. 2013 Aug;45(8):868-76. doi: 10.1038/ng.2652. Epub 2013 Jun 16 PMID: 23770605
  13. Vermeulen R et al. Circulating soluble CD30 and future risk of lymphoma; evidence from two prospective studies in the general population. Cancer Epidemiol Biomarkers Prev. 2011 Sep;20(9):1925-7. PMID: 21784955
  14. Franceschi S et al. Infection with hepatitis B and C viruses and risk of lymphoid malignancies in the European Prospective Investigation into Cancer and Nutrition (EPIC). Cancer Epidemiol Biomarkers Prev. 2011 Jan;20(1):208-14. doi: 10.1158/1055-9965.EPI-10-0889. PMID: 21098651

Contact details/Working Group leader

Roel Vermeulen
Utrecht University
Nieuw Gildestein
Yalelaan 2
3584 CM Utrecht
R.C.H.Vermeulen@uu.nl