Risk of Non–Hodgkin Lymphoma Associated with Polymorphisms in Folate-Metabolizing Genes
| Autor: | Christine F. Skibola, Tracy Lightfoot, Peter J. Adamson, Gareth J. Morgan, Danica R. Skibola, Eve Roman, Eleanor V. Willett, Martyn T. Smith, James M. Allan, Fabio Coppede |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Male
Epidemiology Population Follicular lymphoma 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase Folic Acid hemic and lymphatic diseases medicine Humans Methionine synthase education Methylenetetrahydrofolate Reductase (NADPH2) Glycine Hydroxymethyltransferase education.field_of_study Polymorphism Genetic biology Lymphoma Non-Hodgkin Haplotype Case-control study Genetic Variation DNA Thymidylate Synthase Middle Aged medicine.disease Lymphoma Logistic Models Haplotypes Oncology Case-Control Studies Methylenetetrahydrofolate reductase Immunology biology.protein Cancer research Female Diffuse large B-cell lymphoma |
| Zdroj: | Cancer Epidemiology, Biomarkers & Prevention. 14:2999-3003 |
| ISSN: | 1538-7755 1055-9965 |
| Popis: | Genetic instability, including chromosomal imbalance, is important in the pathogenesis of lymphoproliferative disorders such as non–Hodgkin lymphoma (NHL). DNA synthesis and methylation, which are closely linked to folate metabolism and transport, may be affected by polymorphisms in genes involved in these pathways. Folate metabolism polymorphisms have been linked to acute lymphoblastic leukemia and colorectal cancer. To evaluate whether genetic variation in folate metabolism and transport may have a role in determining the risk of developing NHL, we analyzed several polymorphisms using DNA obtained as part of a large U.K. population-based case-control study of lymphoma. Polymorphisms studied include methylenetetrahydrofolate reductase (MTHFR) 677 C>T and 1298 A>C, methionine synthase (MTR) 2756 A>G, serine hydroxymethyltransferase (SHMT1) 1420 C>T, thymidylate synthase (TYMS) 1494del6 and 28–bp repeat, and reduced folate carrier (RFC) 80 G>A. Increased risks for NHL [odds ratio (OR), 1.48; 95% confidence intervals (CI), 1.12-1.97], and marginal zone lymphoma (OR, 3.38; 95% CI, 1.30-8.82) were associated with the TYMS 2R/3R variant. Marginal increased risks were also observed for diffuse large B cell lymphoma with the TYMS homozygous 6 bp deletion (OR, 1.61; 95% CI, 0.99-2.60) and for follicular lymphoma with RFC 80AA (OR, 1.44; 95% CI, 0.94-2.22) and TYMS 28–bp repeat 2R/3R (OR, 1.45; 95% CI, 0.96-2.2). We observed no association between NHL and haplotypes for MTHFR or TYMS. These findings are somewhat inconsistent with those of others, but may reflect differences in circulating folate levels between study populations. Thus, further investigations are warranted in larger series with dietary information to determine the roles that genetics and folic acid status play in the etiology of lymphoma. (Cancer Epidemiol Biomarkers Prev 2005;14(12):2999–3003) |
| Databáze: | OpenAIRE |
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