The lancet oncology
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The lancet oncology · Jan 2011
ReviewIsocitrate dehydrogenase-1 mutations: a fundamentally new understanding of diffuse glioma?
The discovery of somatic mutations in the gene encoding isocitrate dehydrogenase-1 (IDH1) in glioblastomas was remarkable because the enzyme was not previously identified with any known oncogenic pathway. IDH1 is mutated in up to 75% of grade II and grade III diffuse gliomas. Apart from acute myeloid leukaemia, other tumour types do not carry IDH1 mutations. ⋯ Mutated IDH1 has an altered catalytic activity that results in the accumulation of 2-hydroxyglutarate. Molecularly, IDH1 and IDH2 mutations are heterozygous, affect only a single codon, and rarely occur together. Because IDH1 does not belong to a traditional oncogenic pathway and is specifically and commonly mutated in gliomas, the altered enzymatic activity of IDH1 may provide a fundamentally new understanding of diffuse glioma.
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Children with cancer are increasingly benefiting from new treatment strategies and advances in supportive care, as shown by improvements in both survival and quality-of-life. However, the continuous emergence of new cancer drugs and supportive-care drugs has increased the possibility of harmful drug interactions; health-care providers need to be very cautious when combining drugs. ⋯ We also review the interactions between chemotherapy drugs and food and herbal supplements, and provide recommendations to avoid unwanted and potentially fatal interactions in children with cancer. Because of the constant release of new drugs, health-care providers need to check the most recent references before making recommendations about drug interactions.
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The lancet oncology · Jan 2011
Risk of colorectal and endometrial cancers in EPCAM deletion-positive Lynch syndrome: a cohort study.
Lynch syndrome is caused by germline mutations in MSH2, MLH1, MSH6, and PMS2 mismatch-repair genes and leads to a high risk of colorectal and endometrial cancer. We previously showed that constitutional 3' end deletions of EPCAM can cause Lynch syndrome through epigenetic silencing of MSH2 in EPCAM-expressing tissues, resulting in tissue-specific MSH2 deficiency. We aim to establish the risk of cancer associated with such EPCAM deletions. ⋯ EPCAM deletion carriers have a high risk of colorectal cancer; only those with deletions extending close to the MSH2 promoter have an increased risk of endometrial cancer. These results underscore the effect of mosaic MSH2 deficiency, leading to variable cancer risks, and could form the basis of an optimised protocol for the recognition and targeted prevention of cancer in EPCAM deletion carriers.
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The lancet oncology · Jan 2011
Meta AnalysisAntihypertensive drugs and risk of cancer: network meta-analyses and trial sequential analyses of 324,168 participants from randomised trials.
The risk of cancer from antihypertensive drugs has been much debated, with a recent analysis showing increased risk with angiotensin-receptor blockers (ARBs). We assessed the association between antihypertensive drugs and cancer risk in a comprehensive analysis of data from randomised clinical trials. ⋯ Our analysis refutes a 5·0-10·0% relative increase in the risk of cancer or cancer-related death with the use of ARBs, ACEi, β blockers, diuretics, and CCBs. However, increased risk of cancer with the combination of ACEi and ARBs cannot be ruled out.