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© Oxford University Press 2007.
IN THIS ISSUE
Colony-Stimulating Factors, Breast Cancer, and Leukemia RiskGranulocyte and granulocyte–macrophage colony-stimulating factors (G-CSF), which stimulate hematopoiesis (blood cell production), are used increasingly in women with breast cancer to enable them to endure higher chemotherapy doses than would otherwise be possible. Data from in vitro and epidemiologic studies, however, have suggested that these cytokines may increase the risk of acute myelocytic leukemia (AML) and myelodysplastic syndrome (MDS). Hershman et al. (p. 196) analyzed these outcomes in women in a Surveillance, Epidemiology, and End Results (SEER)–Medicare database who received chemotherapy for breast cancer. Women who had received concurrent growth factor support had about twice the risk of AML or MDS as those who had not. The authors note that the absolute risk was still low but caution that G-CSF use should not be assumed to be risk free.
In an editorial, Touw (p. 183) notes that it remains to be determined whether G-CSF treatment causes AML or MDS. He suggests that only when genes involved in leukemia progression are identified will it be possible to predict whether particular cancer patients should not receive G-CSF treatment to support chemotherapy.
Myocardial Infarction Mortality Risk After Hodgkin Disease
Hodgkin disease survivors have an increased risk of death from myocardial infarction compared with the general population. Swerdlow et al. (p. 206) followed 7,033 British Hodgkin disease patients treated from 1967 through 2000 to study the extent to which specific chemotherapy and radiotherapy regimens contribute to that risk. The myocardial infarction morality rate of the Hodgkin disease patients was 2.5 times that of the general population of England and Wales, and the absolute excess risk was approximately 0.13% per year. The relative risk of death from myocardial infarction decreased with older age at first treatment, but the absolute excess risk increased with older age up to age 65 years at first treatment. The increased risk persisted for at least 25 years after first treatment. The risk was increased for patients treated with supradiaphragmatic radiotherapy, anthracyclines, or vincristine.
In an editorial, Boice (p. 186) writes that additional studies are needed that follow lymphoma survivors for many years. Results of such studies will help to explain the processes and factors that worsen heart function, especially now that patients in remission are living to older ages, when cardiac disease is common. He also recommends investigating the possible interaction between radiotherapy and anthracyclines in the development of heart disease, as well as the influence of other cardiac risk factors, such as cigarette smoking and hyperlipidemia.
The Risk of Second Cancers in Patients with Hairy Cell Leukemia
New treatments have improved survival of patients with hairy cell leukemia, but these patients' risk for second cancers is unknown. Using data collected from the SEER program, Hisada et. al. (p. 215) determined the second cancer incidence and cause-specific mortality of 3,104 survivors of hairy cell leukemia. These patients were at increased relative risk for Hodgkin lymphoma, non-Hodgkin lymphoma, and thyroid cancer. However, the absolute risk was small—the authors estimate that among 10,000 hairy cell leukemia patients, there might be 34 excess cancers per year.
FGF-2, SDF-1, and Hematopoiesis in Myeloid Disorders
Defective bone marrow blood cell development is a serious but potentially reversible complication of clonal myeloid disorders. To better understand its origin, Nakayama et al. (p. 223) evaluated the effect of fibroblast growth factor 2 (FGF-2), which is elevated in patients with clonal myeloid disorders, on bone marrow stromal cell expression of stromal cell–derived factor 1 (SDF-1), a chemokine that is essential for normal hematopoiesis. The authors found that FGF-2 reversibly reduced constitutive SDF-1 mRNA expression and SDF-1 secretion in cultured mouse stromal cells and compromised stromal cell support of the growth and survival of pre–B cells and myeloid lineage cells. Mice treated with FGF-2 showed reversibly reduced bone marrow levels of SDF-1 and induced immature myeloid cell mobilization, extramedullary hematopoiesis, and splenomegaly. The authors conclude that systemic administration of FGF-2 in mice disrupts normal bone marrow hematopoiesis in part through reduced expression of SDF-1. They note that endogenous FGF-2 may represent a potential therapeutic target for bone marrow failure in patients with clonal myeloid disorders.
Quality of Reporting in Cancer Prognostic Marker Study Design
Questions have been raised about the quality of study design and assay methods for cancer prognostic markers. To investigate these issues, Kyzas et al. (p. 236) conducted a meta-analysis of 20 meta-analyses that included 331 studies of cancer prognostic markers. The authors examined blinding, power calculations, prospective versus retrospective design, definition of outcomes, description of variables, assay descriptions, and assay references and found considerable variability across all quality measures. Estimates of prognostic effects from poor-quality studies could be either larger or smaller than the respective effects in good-quality studies. The authors conclude that the reporting quality of design and assay information in cancer prognostic marker studies is often suboptimal, indicating that this literature may be largely unreliable. Improved design and reporting of these studies is warranted.
Identification of DNA Mismatch Repair–Deficient Colorectal Cancer
It is important to identify colorectal cancer patients whose tumors have defects in DNA mismatch repair because these patients often respond differently to therapy than patients without such defects. Tumors with defects in mismatch repair can be identified by the presence of mutations in microsatellite sequences, highly repetitive stretches of DNA in particular locations in the genome. By independently determining whether mismatch repair defects were present based on mismatch repair protein expression, Llor et al. (p. 244) compared the accuracy with which mismatch repair defects were identified when different combinations of microsatellite sequences were probed for mutations. The authors identified a pair of micosatellite sequences whose mutational status more accurately predicted the presence of DNA mismatch repair defects than that of a previously used panel of five microsatellite sequences.
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Del.icio.us What's this?
J Natl Cancer Inst 2007 99: 183-186.
J Natl Cancer Inst 2007 99: 186-187.
J Natl Cancer Inst 2007 99: 196-205.
J Natl Cancer Inst 2007 99: 206-214.
J Natl Cancer Inst 2007 99: 215-222.
J Natl Cancer Inst 2007 99: 223-235.
J Natl Cancer Inst 2007 99: 236-243.
J Natl Cancer Inst 2007 99: 244-252.
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