Mortality From Lymphohematopoietic Malignancies Among Workers in Formaldehyde Industries: The National Cancer Institute Cohort

Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Journal of the National Cancer Institute (Impact Factor: 12.58). 05/2009; 101(10):751-61. DOI: 10.1093/jnci/djp096
Source: PubMed

ABSTRACT Formaldehyde exposure is associated with leukemia in some epidemiological studies. In the National Cancer Institute's formaldehyde cohort, previously followed through December 31, 1979, and updated through December 31, 1994, formaldehyde exposure was associated with an increased risk for leukemia, particularly myeloid leukemia, that increased with peak and average intensity of exposure.
We extended follow-up through December 31, 2004 (median follow-up = 42 years), for 25 619 workers employed at one of 10 formaldehyde-using or formaldehyde-producing plants before 1966. We used Poisson regression to calculate relative risk (RR) estimates and 95% confidence intervals (CIs) to examine associations between quantitative formaldehyde exposure estimates (peak exposure, average intensity and cumulative exposure) and death from lymphohematopoietic malignancies. All statistical tests were two-sided and considered to be significant at P = .05.
When follow-up ended in 2004, there were statistically significant increased risks for the highest vs lowest peak formaldehyde exposure category (> or =4 parts per million [ppm] vs >0 to <2.0 ppm) and all lymphohematopoietic malignancies (RR = 1.37; 95% CI = 1.03 to 1.81, P trend = .02) and Hodgkin lymphoma (RR = 3.96; 95% CI = 1.31 to 12.02, P trend = .01). Statistically nonsignificant associations were observed for multiple myeloma (RR = 2.04; 95% CI = 1.01 to 4.12, P trend > .50), all leukemia (RR = 1.42; 95% CI = 0.92 to 2.18, P trend = .12), and myeloid leukemia (RR = 1.78; 95% CI = 0.87 to 3.64, P trend = .13). There was little evidence of association for any lymphohematopoietic malignancy with average intensity or cumulative exposure at the end of follow-up in 2004. However, disease associations varied over time. For peak exposure, the highest formaldehyde-related risks for myeloid leukemia occurred before 1980, but trend tests attained statistical significance in 1990 only. After the mid-1990s, the formaldehyde-related risk of myeloid leukemia declined.
Evaluation of risks over time suggests a possible link between formaldehyde exposure and lymphohematopoietic malignancies, particularly myeloid leukemia but also perhaps Hodgkin lymphoma and multiple myeloma. Observed patterns could be due to chance but are also consistent with a causal association within the relatively short induction-incubation periods characteristic of leukemogenesis. Further epidemiological study and exploration of potential molecular mechanisms are warranted.

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    • "According to another survey conducted by the National Toxicology Program of the United States, statistically significant increased risks (RR = 1.42, 95% CI = 0.92 to 2.18) were found for all lymphohematopoietic cancers combined, for leukemias combined, and for myeloid leukemia among persons occupationally exposed to any form of formaldehyde including formalin. Relative risks increased with increasing peak exposure [11]. To date, there is no epidemiological survey of various cancers in Bangladesh or the impact of this chronic exposure to carcinogens throughout the population reported. "
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    ABSTRACT: Here, we report the phase distribution of chronic myeloid leukemia (CML), defined based on the World Health Organization criteria, among 63 patients in Bangladesh. All patients were diagnosed based on complete blood count, bone marrow examination including bone marrow aspiration and reverse-transcriptase polymerase chain reaction (RT-PCR). Out of 63 patients, 42 were male and 21 were female. The mean age of the subjects was 37.4 years, with an age range of 17-60 years. The majority of patients (86%) were classified in the chronic phase (CP), 7 (11%) in the accelerated phase (AP) and two (3%) in blast crisis (BC). The most frequent patient age ranges were 21-30 years for CP, 41-50 years for AP and 41-50 years for BC. The Philadelphia chromosome was detected in 48 patients by RT-PCR. The mean total leukocyte counts, platelet counts, hemoglobin levels and marrow blast frequencies were 101 x 109/L, 409 x 109/L, 12.2 g/dl and 2.8% for CP; 121 x 109/L, 418 x 109/L, 8.7 g/dl and 15% for AP and 311 x 109/L, 396 x 109/L, 9.2 g/dl and 26% for BC, respectively. This study concluded that most CML patients in Bangladesh are from a younger age group (31-40 years). In addition, males were more commonly affected, although females were afflicted with this disease at a younger age.
    BMC Research Notes 03/2014; 7(1):142. DOI:10.1186/1756-0500-7-142
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    • "Since then, hundreds of reports have been published focusing on the health effects of formaldehyde inhalation exposure (IARC, 2012; NTP, 2011). Formaldehyde inhalation exposure has been associated with several detrimental health effects including increased risk of childhood asthma (McGwin et al., 2010), upper respiratory tract infections (Lyapina et al., 2004), nasopharyngeal cancer (Hauptmann et al., 2004), and leukemia (Beane Freeman et al., 2009). Formaldehyde is currently classified as a known human carcinogen by the International Agency for Research on Cancer (IARC, 2012) and the National Toxicology Program (NTP, 2011). "
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    ABSTRACT: MicroRNAs (miRNAs) are critical regulators of gene expression, yet much remains unknown regarding their changes resulting from environmental exposures as they influence cellular signaling across various tissues. We set out to investigate miRNA responses to formaldehyde, a critical air pollutant and known carcinogen that disrupts miRNA expression profiles. Rats were exposed by inhalation to either 0 or 2 ppm formaldehyde for 7 days, 28 days, or 28 days followed by a 7 day recovery. Genome-wide miRNA expression profiles were assessed within the nasal respiratory epithelium, circulating white blood cells (WBC), and bone marrow (BM). MiRNAs showed altered expression in the nose and WBC, but not the BM. Notably in the nose, miR-10b and members of the let-7 family, known nasopharyngeal carcinoma players, showed decreased expression. To integrate miRNA responses with transcriptional changes, genome-wide mRNA profiles were assessed in the nose and WBC. While formaldehyde-induced changes in miRNA and transcript expression were largely tissue-specific, pathway analyses revealed an enrichment of immune system/inflammation signaling in the nose and WBC. Specific to the nose was enrichment for apoptosis/proliferation signaling, involving let-7a, let-7c, and let-7f. Across all tissues and time points assessed, miRNAs were predicted to regulate between 7 and 35% of the transcriptional responses, and were suggested to play a role in signaling processes including immune/inflammation-related pathways. These data inform our current hypothesis that formaldehyde-induced inflammatory signals originating in the nose may drive WBC effects.
    Toxicological Sciences 12/2013; 138(1). DOI:10.1093/toxsci/kft267 · 3.85 Impact Factor
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    • "Both SMRs and RRs were estimated using EPICURE software [Preston et al., 1996] and all tests were two-sided at a 5% significance level. All metrics were considered as time-dependent lagged exposures, that is, ignoring the most recent exposure that occurred during a fixed time interval prior to each worker's end of follow-up, as was done for previous analyses from this cohort [Hauptmann et al., 2003, 2004; Beane Freeman et al., 2009]. We evaluated the effect of changing the lag interval (2–20 years) and found little consequence on point estimates. "
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    ABSTRACT: Formaldehyde, a widely used chemical, is considered a human carcinogen. We extended follow-up of the largest industrial cohort of workers in formaldehyde industries (n = 25,619) by 10 years through 2004. Standardized mortality ratios (SMRs) and rate ratios (RRs) were calculated for deaths from solid tumors using quantitative formaldehyde exposure estimates. During 998,239 person-years, 13,951 deaths occurred. With one additional death, previously observed excesses for nasopharyngeal cancer (n = 10) persisted for peak, average intensity and cumulative exposure; RRs in the highest exposure categories were 7.66 (95% CI: 0.94, 62.34), P-trend = 0.005, 11.54 (95% CI: 1.38, 96.81), P-trend = 0.09, and 2.94 (95% CI: 0.65, 13.28), P-trend = 0.06, respectively. For all cancer, solid tumors and lung cancer, SMRs among exposed workers were elevated, but internal analyses revealed no positive associations with formaldehyde exposure. Consistent with previous analyses of this cohort, this update continues to suggest a link between formaldehyde exposure and nasopharyngeal cancer. Am. J. Ind. Med. 2013. © 2013 Wiley Periodicals, Inc.
    American Journal of Industrial Medicine 09/2013; 56(9). DOI:10.1002/ajim.22214 · 1.74 Impact Factor
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