Acrylamide, a probable human carcinogen, is formed in several foods during high-temperature processing. So far, epidemiological studies have not shown any association between human cancer risk and dietary exposure to acrylamide. The purpose of this study was to conduct a nested case control study within a prospective cohort study on the association between breast cancer and exposure to acrylamide using biomarkers. N-terminal hemoglobin adduct levels of acrylamide and its genotoxic metabolite, glycidamide in red blood cells were analyzed (by LC/MS/MS) as biomarkers of exposure on 374 breast cancer cases and 374 controls from a cohort of postmenopausal women. The adduct levels of acrylamide and glycidamide were similar in cases and controls, with smokers having much higher levels (approximately 3 times) than nonsmokers. No association was seen between acrylamide-hemoglobin levels and breast cancer risk neither unadjusted nor adjusted for the potential confounders HRT duration, parity, BMI, alcohol intake and education. After adjustment for smoking behavior, however, a positive association was seen between acrylamide-hemoglobin levels and estrogen receptor positive breast cancer with an estimated incidence rate ratio (95% CI) of 2.7 (1.1-6.6) per 10-fold increase in acrylamide-hemoglobin level. A weak association between glycidamide hemoglobin levels and incidence of estrogen receptor positive breast cancer was also found, this association, however, entirely disappeared when acrylamide and glycidamide hemoglobin levels were mutually adjusted.
Acrylamide exposure measured by food frequency questionnaire and hemoglobin adduct levels and prostate cancer risk in the Cancer of the Prostate in Sweden Study.
Acrylamide, a probable human carcinogen, is formed during the cooking of many commonly consumed foods. Data are scant on whether dietary acrylamide represents an important cancer risk in humans. We studied the association between acrylamide and prostate cancer risk using 2 measures of acrylamide exposure: intake from a food frequency questionnaire (FFQ) and acrylamide adducts to hemoglobin. We also studied the correlation between these 2 exposure measures. We used data from the population-based case-control study Cancer of the Prostate in Sweden (CAPS). Dietary data was available for 1,499 cases and 1,118 controls. Hemoglobin adducts of acrylamide were measured in blood samples from a subset of 170 cases and 161 controls. We calculated odds ratios (ORs) for the risk of prostate cancer in high versus low quantiles of acrylamide exposure using logistic regression. The correlation between FFQ acrylamide intake and acrylamide adducts in non-smokers was 0.25 (95% confidence interval: 0.14-0.35), adjusted for age, region, energy intake, and laboratory batch. Among controls the correlation was 0.35 (95% CI: 0.21-0.48); among cases it was 0.15 (95% CI: 0.00-0.30). The OR of prostate cancer for the highest versus lowest quartile of acrylamide adducts was 0.93 (95% CI: 0.47-1.85, p-value for trend = 0.98). For FFQ acrylamide, the OR of prostate cancer for the highest versus lowest quintile was 0.97 (95% CI: 0.75-1.27, p trend = 0.67). No significant associations were found between acrylamide exposure and risk of prostate cancer by stage, grade, or PSA level. Acrylamide adducts to hemoglobin and FFQ-measured acrylamide intake were moderately correlated. Neither measure of acrylamide exposure-hemoglobin adducts or FFQ-was associated with risk of prostate cancer.
Our purpose was to investigate whether alcohol (ethanol) consumption could have an influence on the metabolism of acrylamide to glycidamide in humans exposed to acrylamide through food. We studied a subsample from a population-based case-control study of prostate cancer in Sweden (CAPS). Questionnaire data for alcohol intake estimates was compared to the ratio of hemoglobin-adduct levels for acrylamide and glycidamide, used as a measure of individual differences in metabolism. Data from 161 non-smoking men were processed with regard to the influence of alcohol on the metabolism of acrylamide to glycidamide. A negative, linear trend of glycidamide-adduct to acrylamide-adduct-level ratios with increasing alcohol intake was observed and the strongest association (p-value for trend=0.02) was obtained in the group of men with the lowest adduct levels (47 pmol/g globin) when alcohol intake was stratified by acrylamide-adduct levels. The observed trend is likely due to a competitive effect between ethanol and acrylamide as both are substrates for cytochrome P450 2E1. Our results, strongly indicating that ethanol influence metabolism of acrylamide to glycidamide, partly explain earlier observations of only low to moderate associations between questionnaire data on dietary acrylamide intake and hemoglobin-adduct levels.
BACKGROUND: The purpose of this study was to determine the incidence, risk factors and prognostic impact of anaemia and thrombocytopenia in patients with bone metastases (BM) from prostate cancer. METHODS: Retrospective cohort study including 51 consecutive patients treated at a community hospital. Twenty-nine patients (57%) received taxotere after diagnosis of BM. RESULTS: Haemoglobin (Hb)
Department of Oncology, University of Tampere and Tampere University Hospital, B.O.X. 607, FIN 33101, Tampere, Finland. Pirkko-Liisa.Kellokumpu-Lehtinen@uta.fi
Anaemia is very frequently diagnosed among cancer patients. Use of erythropoietins has proved to be effective in reducing the need of transfusions and enhancing patients' quality of life, but may also have detrimental effects in treating nonanemic asymptomatic patients. We assessed the frequency of anaemia and the frequency with which it was diagnosed and treated in different types of solid tumours treated at outpatient chemotherapy policlinics.
During the study period, altogether 733 consecutive subjects received chemotherapy at the five Finnish University Hospitals. Their data were collected. The physician who was responsible for the chemotherapy treatment was unaware of the survey. The response to anaemia (treated or not, the modality of treatment) were established from patients records; 69% were females, mean age was 61 years (range, 24-92).
The median haemoglobin level was 12.7 g/dL (range, 8.9-15.5 g/dL). About one third of the patients (200/733, 27%) had a value less than 12 g/dL. In only 15% of these cases was there any documentation of response or a possible treatment option for anaemia. On the other hand, only 12% of all patients (N=91) had a haemoglobin value less than 11 g/dL. However, in most of them anaemia had not been considered; in only 25% of cases was an active treatment option selected.
According to our survey, anaemia was less common in our patients than in the European Cancer Anaemia Survey. Only a minority of chemotherapy patients receiving their treatments as outpatients would need active treatment for their anaemia.
Department of Materials and Environmental Chemistry, Environmental Chemistry Unit, Arrhenius Laboratory, Stockholm University, SE-106 91 Stockholm, Sweden.
The knowledge about fetal exposure to acrylamide/glycidamide from the maternal exposure through food is limited. Acrylamide, glycidamide, and ethylene oxide are electrophiles and form adducts with hemoglobin (Hb), which could be used for in vivo dose measurement. In this study, a method for analysis of Hb adducts by liquid chromatography-mass spectrometry, the adduct FIRE procedure, was applied to measurements of adducts from these compounds in maternal blood samples (n = 87) and umbilical cord blood samples (n = 219). The adduct levels from the three compounds, acrylamide, glycidamide, and ethylene oxide, were increased in tobacco smokers. Highly significant correlations were found between cord and maternal blood with regard to measured adduct levels of the three compounds. The mean cord/maternal hemoglobin adduct level ratios were 0.48 (range 0.27-0.86) for acrylamide, 0.38 (range 0.20-0.73) for glycidamide, and 0.43 (range 0.17-1.34) for ethylene oxide. In vitro studies with acrylamide and glycidamide showed a lower (0.38-0.48) rate of adduct formation with Hb in cord blood than with Hb in maternal blood, which is compatible with the structural differences in fetal and adult Hb. Together, these results indicate a similar life span of fetal and maternal erythrocytes. The results showed that the in vivo dose in fetal and maternal blood is about the same and that the placenta gives negligible protection of the fetus to exposure from the investigated compounds. A trend of higher levels of the measured adducts in cord blood with gestational age was observed, which may reflect the gestational age-related change of the cord blood Hb composition toward a higher content of adult Hb. The results suggest that the Hb adduct levels measured in cord blood reflect the exposure to the fetus during the third trimester. The evaluation of the new analytical method showed that it is suitable for monitoring of background exposures of the investigated electrophilic compounds in large population studies.
Anemia and iron deficiency in inflammatory bowel disease: an open, prospective, observational study on diagnosis, treatment with ferric carboxymaltose and quality of life.
Iron deficiency and anemia are being increasingly recognized as a complication of inflammatory bowel disease (IBD). The aim of this study was to observe, in a non-interventional way, how Swedish gastroenterologists adhere to guidelines in IBD outpatients treated with intravenous ferric carboxymaltose (FCM), and the result of treatment.
Altogether 394 IBD patients (Crohn's disease (CD) 60%, ulcerative colitis (UC) 40%) from 14 centers were included. Group A (n = 216) was observed from November 2008 and group B (n = 178) from March 2010. Time of observation ranged from 12 to 29 months.
S-Ferritin (?mol/l) and transferrin saturation (T-Sat; %) were recorded at baseline in 62% and 50% in group A. Median values for Hb, ferritin and T-Sat at baseline were 111 g/l, 10 ?mol/l and10%, respectively, and 134 g/l, 121 ?mol/l and 20% after iron treatment (p
To investigate detectability of anemia, its clinical and pathophysiological features in patients with diabetic nephropathy (DN).
The trial included 1020 patients with type 1 and 2 diabetes mellitus (DM). DN was diagnosed in 50% of them. Incidence of anemia was compared in 92 DN patients in type 1 DM and in 230 patients with chronic glomerulonephritis (CGN). Concentration of erythropoietin (EP) in blood serum was measured in 94 DN patients in type 1 and 2 DM.
Anemia develops in type 1 and 2 DM patients free of DN and unaffected renal filtration function (glomerular filtration rate--GFR > 60 ml/min 1.73 m2) was 23.3 and 18.3%, respectively. In DN patients incidence rate of anemia depended on GFR and increased with growing severity of renal failure reaching 85.7% in GFR
Anemia in early rheumatoid arthritis is associated with interleukin 6-mediated bone marrow suppression, but has no effect on disease course or mortality.
OBJECTIVE: Anemia of chronic disease (ACD) is the most common extraarticular manifestation of rheumatoid arthritis (RA), but there is limited information on the cause and consequences of ACD. We investigated the prevalence, relation with proinflammatory cytokines, and effect on disease outcome of ACD in patients with RA. METHODS: The presence of anemia was analyzed in a cohort of 111 consecutive patients with early RA. Anemia was related to markers of erythropoiesis and inflammation [clinically and by levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum interleukin 1beta (IL-1beta), IL-2, IL-6, IL-8, and tumor necrosis factor-alpha]. The frequency of various disease outcomes during the mean followup of 74 months was compared between ACD and nonanemic patients. RESULTS: ACD was present in 25% during the first year of disease. ACD was associated with higher CRP (45 vs 22 g/l; p = 0.04) and ESR levels (54 vs 33 mm/h; p = 0.002). Hemoglobin levels were inversely correlated with serum erythropoietin (p = 0.003) in univariate analysis, but in multivariate analysis only ESR (p = 0.005) and IL-6 (p = 0.056) remained as independent predictors of hemoglobin levels. Presence of ACD was not associated with later development of disease manifestations or mortality. CONCLUSION: While ACD affected 25% of patients with RA early in the disease course, this had no influence on disease outcome including mortality during the following 6 years. The association between IL-6 and ACD suggests that IL-6-mediated bone marrow suppression is the main mechanism for development of ACD in RA.
Previous results [(1988) Arct. Med. Res. 47, 83-88] have shown that hemoglobin from reindeer is characterized by a low overall heat of oxygenation. This particular aspect has been investigated further in a series of precise oxygen equilibrium experiments. The results obtained show a peculiar dependence of the temperature effect on the fractional saturation of hemoglobin with oxygen, which could be regarded as a very interesting case of molecular adaptation to extreme environmental conditions.
