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Nonsteroidal anti-inflammatory drug and acetaminophen use and risk of adult myeloid leukemia.

ABSTRACT: Little is known about the causes of adult leukemia. A few small studies have reported a reduced risk associated with regular use of nonsteroidal anti-inflammatory drugs (NSAID).In a population-based case-control study, we evaluated analgesic use among 670 newly diagnosed myeloid leukemia cases [including 420 acute myeloid leukemias (AML) and 186 chronic myeloid leukemias (CML)] and 701 controls aged 20 to 79 years. Prior use of aspirin, ibuprofen, acetaminophen, other NSAIDs, and COX-2 inhibitors was assessed and included frequency, duration, and quantity. ORs and 95% CIs were calculated using unconditional logistic regression adjusting for potential confounders.Regular/extra strength aspirin use was inversely associated with myeloid leukemia in women (OR = 0.59, 95% CI = 0.37-0.93) but not in men (OR = 0.85, 95% CI = 0.58-1.24). In contrast, acetaminophen use was associated with an increased risk of myeloid leukemia in women only (OR = 1.60, 95% CI = 1.04-2.47). These relationships were stronger with increasing dose and duration. When stratified by leukemia type, aspirin use was inversely associated with AML and CML in women. No significant overall associations were found with ibuprofen or COX-2 inhibitors for either sex; however, a decreased risk was observed with other anti-inflammatory analgesic use for women with AML or CML (OR = 0.47, 95% CI = 0.22-0.99; OR = 0.31, 95% CI = 0.10-0.92, respectively).Our results provide additional support for the chemopreventive benefits of NSAIDs, at least in women. Because leukemia ranks fifth in person-years of life lost due to malignancy, further investigation is warranted.NSAIDs may reduce, whereas acetaminophen may increase, myeloid leukemia risk in women.

SUBMITTER: Ross JA

PROVIDER: S-EPMC3153558 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Nonsteroidal anti-inflammatory drug and acetaminophen use and risk of adult myeloid leukemia.

Ross Julie A JA Blair Cindy K CK Cerhan James R JR Soler John T JT Hirsch Betsy A BA Roesler Michelle A MA Higgins Rodney R RR Nguyen Phuong L PL

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20110629 8

<h4>Background</h4>Little is known about the causes of adult leukemia. A few small studies have reported a reduced risk associated with regular use of nonsteroidal anti-inflammatory drugs (NSAID).<h4>Methods</h4>In a population-based case-control study, we evaluated analgesic use among 670 newly diagnosed myeloid leukemia cases [including 420 acute myeloid leukemias (AML) and 186 chronic myeloid leukemias (CML)] and 701 controls aged 20 to 79 years. Prior use of aspirin, ibuprofen, acetaminophen ...[more]

PMID: 21715605

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Project description:BackgroundLipid transfer protein (LTP), an abundant protein in fruits, vegetables, and nuts, is a common food allergen in Mediterranean areas causing diverse allergic reactions. Approximately 40% of food-related anaphylaxis induced by LTPs requires nonsteroidal anti-inflammatory drugs (NSAIDs) as a triggering cofactor.ObjectiveWe sought to better understand the determinants of NSAID-dependent and NSAID-independent LTP-induced anaphylaxis (LTP-A).MethodsSelection of patients was based on a proved clinical history of NSAID-dependent or NSAID-independent anaphylaxis to LTPs, positive skin prick test response to LTPs, and serum LTP IgE. Whole-transcriptome (RNA sequencing) analysis of blood cells from 14 patients with NSAID-related LTP-A (NSAID-LTP-A), 7 patients with LTP-A, and 13 healthy control subjects was performed to identify distinct gene expression signatures.ResultsExpression of genes regulating gastrointestinal epithelial renewal was altered in both patient sets, particularly in those with LTP-A, who also presented with gene expression profiles characteristic of an inflammatory syndrome. These included altered B-cell pathways, increased neutrophil activation markers, and increased reactive oxygen species levels. Increased expression of the IgG receptor (CD64) in patients with LTP-A was mirrored by the presence of LTP-specific IgG1 and IgG3. Conversely, patients with NSAID-LTP-A were characterized by reduced expression of IFN-γ-regulated genes and IFN-γ levels, as well as upregulated expression of adenosine receptor 3 (ADORA3) and genes related to adenosine metabolism.ConclusionsGene ontology analysis suggests disturbances in gut epithelial homeostasis in both groups with LTP-A, with potential integrity breaches in patients with LTP-A that might explain their distinct inflammatory signatures. Differential regulation in patients with LTP-A and those with NSAID-LTP-A of the IFN-γ pathway, IgG receptors, and ADORA3 might provide the pathogenic basis of their distinct responses.

Dataset Information

Nonsteroidal anti-inflammatory drug and acetaminophen use and risk of adult myeloid leukemia.

Publications

Nonsteroidal anti-inflammatory drug and acetaminophen use and risk of adult myeloid leukemia.

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