Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cancer is also an epigenetic disease. The main epigenetic modification in humans is DNA methylation. Transformed cells undergo a dramatic change in their DNA methylation patterns: certain CpG islands located in the promoter regions of tumor-suppressor genes become hypermethylated and the contiguous gene rests silenced and this phenomenon occurs in an overall genomic environment of DNA hypomethylation. The profile of CpG island hypermethylation in hematologic malignancies is an epigenetic signature unique for each subtype of leukemia or lymphoma. Although the most widely studied genes are the cell-cycle inhibitors p15INK4b and p16INK4a (specially in AML and ALL), the list of methylation-repressed genes in these neoplasms is expanding very rapidly, including MGMT, RARB2, CRBP1, SOCS-1, CDH1, DAPK1, and others. A necessary cross-talk between genetic alterations and DNA methylation exists: certain chromosomal translocations may induce hypermethylation, such as the PML-RARa, or attract methylation, such as BCR-ABL, but DNA hypomethylation can be the culprit behind the genesis of certain abnormal recombination events. From a translational standpoint, hypermethylation can be used as a marker of recurrent disease or progression, for example, in MDS, or response to chemotherapy, such as MGMT methylation in B-cell non-Hodgkin's lymphoma. Furthermore, promising studies using DNA demethylating agents and histone deacetylase inhibitors are underway to awake these dormant tumor-suppressor genes for a better treatment of the patient with a hematologic malignancy.
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PMID:Profiling aberrant DNA methylation in hematologic neoplasms: a view from the tip of the iceberg. 1458 79

The main objective of this study was to test the hypothesis that genetic variations in DNA repair genes may modify the association between occupational exposure to solvents and the risk of non-Hodgkin's lymphoma (NHL). A population-based case-control study was conducted on Connecticut women including 518 histologically confirmed incident NHL cases and 597 controls. Unconditional logistic regression models were used to estimate the odds ratios and effect modification from the 30 single nucleotide polymorphisms in 16 DNA repair genes of the association between solvent exposure and the risk of NHL overall and subtypes. Single nucleotide polymorphisms in MGMT (rs12917) and NBS1 (rs1805794) significantly modified the association between exposure to chlorinated solvents and the risk of NHL (Pfor interaction=0.0003 and 0.0048, respectively). After stratification by major NHL histological subtypes, MGMT (rs12917) modified the association between chlorinated solvents and the risk of diffuse large B-cell lymphoma (Pfor interaction=0.0027) and follicular lymphoma (Pfor interaction=0.0024). A significant interaction was also observed between occupational exposure to benzene and BRCA2 (rs144848) for NHL overall (Pfor interaction=0.0042). Our study results suggest that genetic variations in DNA repair genes modify the association between occupational exposure to solvents and the risk of NHL.
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PMID:Occupational solvent exposure, genetic variation of DNA repair genes, and the risk of non-Hodgkin's lymphoma. 2243 Apr 43