| 1. |
- Opstal-van Winden, Annemieke W. J., et al.
(författare)
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Searching for early breast cancer biomarkers by serum protein profiling of pre-diagnostic serum; a nested case-control study
- 2011
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Serum protein profiles have been investigated frequently to discover early biomarkers for breast cancer. So far, these studies used biological samples collected at or after diagnosis. This may limit these studies' value in the search for cancer biomarkers because of the often advanced tumor stage, and consequently risk of reverse causality. We present for the first time pre-diagnostic serum protein profiles in relation to breast cancer, using the Prospect-EPIC (European Prospective Investigation into Cancer and nutrition) cohort. Methods: In a nested case-control design we compared 68 women diagnosed with breast cancer within three years after enrollment, with 68 matched controls for differences in serum protein profiles. All samples were analyzed with SELDI-TOF MS (surface enhanced laser desorption/ionization time-of-flight mass spectrometry). In a subset of 20 case-control pairs, the serum proteome was identified and relatively quantified using isobaric Tags for Relative and Absolute Quantification (iTRAQ) and online two-dimensional nano-liquid chromatography coupled with tandem MS (2D-nanoLC-MS/MS). Results: Two SELDI-TOF MS peaks with m/z 3323 and 8939, which probably represent doubly charged apolipoprotein C-I and C3a des-arginine anaphylatoxin (C3a(desArg)), were higher in pre-diagnostic breast cancer serum (p = 0.02 and p = 0.06, respectively). With 2D-nanoLC-MS/MS, afamin, apolipoprotein E and isoform 1 of inter-alpha trypsin inhibitor heavy chain H4 (ITIH4) were found to be higher in pre-diagnostic breast cancer (p < 0.05), while alpha-2-macroglobulin and ceruloplasmin were lower (p < 0.05). C3a(desArg) and ITIH4 have previously been related to the presence of symptomatic and/or mammographically detectable breast cancer. Conclusions: We show that serum protein profiles are already altered up to three years before breast cancer detection.
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| 2. |
- Barregård, Lars, 1948, et al.
(författare)
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Human and Methodological Sources of Variability in the Measurement of Urinary 8-Oxo-7,8-dihydro-2 '-deoxyguanosine
- 2013
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Ingår i: Antioxidants and Redox Signaling. - : Mary Ann Liebert Inc. - 1523-0864 .- 1557-7716. ; 18:18, s. 2377-2391
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is a widely used biomarker of oxidative stress. However, variability between chromatographic and ELISA methods hampers interpretation of data, and this variability may increase should urine composition differ between individuals, leading to assay interference. Furthermore, optimal urine sampling conditions are not well defined. We performed inter-laboratory comparisons of 8-oxodG measurement between mass spectrometric-, electrochemical- and ELISA-based methods, using common within-technique calibrants to analyze 8-oxodG-spiked phosphate-buffered saline and urine samples. We also investigated human subject- and sample collection-related variables, as potential sources of variability. Results: Chromatographic assays showed high agreement across urines from different subjects, whereas ELISAs showed far more inter-laboratory variation and generally overestimated levels, compared to the chromatographic assays. Excretion rates in timed 'spot' samples showed strong correlations with 24 h excretion (the 'gold' standard) of urinary 8-oxodG (r(p) 0.67-0.90), although the associations were weaker for 8-oxodG adjusted for creatinine or specific gravity (SG). The within-individual excretion of 8-oxodG varied only moderately between days (CV 17% for 24 h excretion and 20% for first void, creatinine-corrected samples). Innovation: This is the first comprehensive study of both human and methodological factors influencing 8-oxodG measurement, providing key information for future studies with this important biomarker. Conclusion: ELISA variability is greater than chromatographic assay variability, and cannot determine absolute levels of 8-oxodG. Use of standardized calibrants greatly improves intra-technique agreement and, for the chromatographic assays, importantly allows integration of results for pooled analyses. If 24 h samples are not feasible, creatinine- or SG-adjusted first morning samples are recommended.
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| 3. |
- Lyngso, J., et al.
(författare)
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Menstrual cycle characteristics in fertile women from Greenland, Poland and Ukraine exposed to perfluorinated chemicals: a cross-sectional study
- 2014
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 29:2, s. 359-367
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Tidskriftsartikel (refereegranskat)abstract
- Does perfluorooctane sulfonate (PFOS) and perfluorooctanate (PFOA) exposure disrupt the menstrual cyclicity? The female reproductive system may be sensitive to PFOA exposure, with longer menstrual cycle length at higher exposure. PFOS and PFOA are persistent man-made chemicals. Experimental animal studies suggest they are reproductive toxicants but epidemiological findings are inconsistent. A cross-sectional study including 1623 pregnant women from the INUENDO cohort enrolled during antenatal care visits between June 2002 and May 2004 in Greenland, Poland and Ukraine. Information on menstrual cycle characteristics was obtained by questionnaires together with a blood sample from each pregnant woman. Serum concentrations of PFOS and PFOA were measured by liquid chromatography tandem mass spectrometry. Multiple imputations were performed to account for missing data. The association between PFOS/PFOA and menstrual cycle length (short cycle: 24 days, long cycle: 32 days) and irregularities (7 days in difference between cycles) was analyzed using logistic regression with tertiles of exposure. Estimates are given as adjusted odds ratios (ORs) with 95 confidence intervals (CIs). Higher exposure levels of PFOA were associated with longer menstrual cycles in pooled estimates of all three countries. Compared with women in the lowest exposure tertile, the adjusted OR of long cycles was 1.8 (95 CI: 1.0; 3.3) among women in the highest tertile of PFOA exposure. No significant associations were observed between PFOS exposure and menstrual cycle characteristics. However, we observed a tendency toward more irregular cycles with higher exposure to PFOS [OR 1.7 (95 CI: 0.8; 3.5)]. The overall response rate was 45.3 with considerable variation between countries (91.3 in Greenland, 69.1 in Poland and 26.3 in Ukraine). Possible limitations in our study include varying participation rates across countries; a selected study group overrepresenting the most fertile part of the population; retrospective information on menstrual cycle characteristics; the determination of cut-points for all three outcome variables; and lacking information on some determinants of menstrual cycle characteristics, such as stress, physical activity, chronic diseases and gynecological disorders, thus confounding cannot be excluded. The generalizability of the study results is restricted to fertile women who manage to conceive and women who do not use oral contraceptives when getting pregnant or within 2 months before getting pregnant. To our knowledge only one previous epidemiological study has addressed the possible association between perfluorinated chemical exposure and menstrual disturbances. Though pointing toward different disturbances in cyclicity, both studies suggest that exposure to PFOA may affect the female reproductive function. This study contributes to the limited knowledge on effects of exposure to PFOA and PFOS on female reproductive function and suggests that the female reproductive system may be affected by environmental exposure to PFOA. Supported by a scholarship from Aarhus University Research Foundation. The collection of questionnaire data and blood samples was part of the INUENDO project supported by The European Commission (Contract no. QLK4-CT-2001-00 202), . The Ukrainian part of the study was possible by a grant from INTAS (project 012 2205). Determination of PFOA and PFOS in serum was part of the CLEAR study () supported by the European Commissions 7th Framework Program (FP7-ENV-2008-1-226217). No conflict of interest declared.
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| 4. |
- Jönsson, Bo AG, et al.
(författare)
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Tidstrender för och halter av perfluorerade alkylsyror (PFAAs) i serum samt ftalatmetaboliter och alkylfenoler i urin hos unga svenska män och kvinnor– Resultat från den fjärde uppföljningsundersökningen år 2013
- 2014
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Bakgrund:Studier av tidstrender är viktiga för riskvärdering, för att följa resultat av interventioner och för åtgärder för att minska exponeringen. Studiens huvudsyfte har varit att undersöka halter och tidstrender för perfluorerade kemikalier i serum samt ftalatmetaboliter och alkylfenoler i urin hos unga män och kvinnor. För detta har vi tidigare valt att använda oss av mönstringsundersökningen, som de flesta svenska män hittills har genomgått vid omkring 18 års ålder. När mönstringen nu slopats har vi istället samlade in prover från gymnasieelever i den sista årskursen. Vi utökade även studien så både kvinnor och män nu studeras.Metoder:Unga personer från fem olika år har hittills studerats. År 2000 samlades serumprover från 274 mönstrande och urinprover från 234, år 2004 samlades serum- och urinprover från 200 mönstrande, år 2006 serumprover från 200 mönstrande och åren 2009-2010 (benämns som 2010 i den fortsatta rapporten) serumprover från 100 mönstrande och urinprover från 314 samt slutligen år 2013 serum och urinprover från 107 kvinnliga och 97 manliga gymnasieelever i tredje årskursen. I den nu aktuella uppföljningen analyserades 15 perfluorerade alkylsyror (PFAAs) i serum, 10 ftalatmetaboliter från fem olika ftalater, fyra alkylfenoler av vilka tre var bisfenoler samt triklosan i urin. Dessutom analyserades metaboliterna till pesticiderna klorpyrifos (triklorpyridinol ,TCP) och gruppen pyretroider (3-fenoxibensoesyra, 3-PBA) samt 1-hydroxypyren en biomarkör för PAH exponering i urin. Bisfenol A analyserades även i 258 urinprover från 2010. Samtliga analyser utfördes med vätskekromatografi kopplat till en tandem masspektrometer. Trender analyserades med Jonckheere-Terpstra testet och skillnader mellan grupper med Mann-Whitneys U test.Resultat:Halterna av de flesta PFAAs i serum verkade minska mellan 2010 och 2013. De kreatininjusterade halterna för MEP, MBP, MBzP och MEHP för åren 2000, 2004, 2010 och 2013 visade alla en sjunkande trend. Dessutom visade inte halterna av diisononylftalatmetaboliterna en ökande trend vilket hade förväntats från andra studier. Halterna av BPA verkade minska relativt kraftigt mellan 2010 och 2013 vilket så vitt vi vet är den första tidstenden för denna substans.
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| 5. |
- Jørgensen, Kristian T., et al.
(författare)
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Perfluoroalkyl substances and time to pregnancy in couples from Greenland, Poland and Ukraine
- 2014
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Ingår i: Environmental Health: A Global Access Science Source. - 1476-069X. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Perfluoroalkyl substances (PFAS) are suggested to affect human fecundity through longer time to pregnancy (TTP). We studied the relationship between four abundant PFAS and TTP in pregnant women from Greenland, Poland and Ukraine representing varying PFAS exposures and pregnancy planning behaviors. Methods: We measured serum levels of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonic acid (PFHxS) and perfluorononanoic acid (PFNA) in 938 women from Greenland (448 women), Poland (203 women) and Ukraine (287 women). PFAS exposure was assessed on a continuous logarithm transformed scale and in country-specific tertiles. We used Cox discrete-time models and logistic regression to estimate fecundability ratios (FRs) and infertility (TTP >13 months) odds ratios (ORs), respectively, and 95% confidence intervals (CI) according to PFAS levels. Adjusted analyses of the association between PFAS and TTP were done for each study population and in a pooled sample. Results: Higher PFNA levels were associated with longer TTP in the pooled sample (log-scale FR∈=∈0.80; 95% CI 0.69-0.94) and specifically in women from Greenland (log-scale FR∈=∈0.72; 95% CI 0.58-0.89). ORs for infertility were also increased in the pooled sample (log-scale OR∈=∈1.53; 95% CI 1.08-2.15) and in women from Greenland (log-scale OR∈=∈1.97; 95% CI 1.22-3.19). However, in a sensitivity analysis of primiparous women these associations could not be replicated. Associations with PFNA were weaker for women from Poland and Ukraine. PFOS, PFOA and PFHxS were not consistently associated with TTP. Conclusions: Findings do not provide consistent evidence that environmental exposure to PFAS is impairing female fecundity by delaying time taken to conceive.
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| 6. |
- Littorin, Margareta, et al.
(författare)
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Analyser av pesticider i urin hos skånska kvinnor 2010
- 2013
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Såväl allmänbefolkning som vissa yrkesarbetande grupper exponeras för kemiska bekämpningsmedel (BM), allmänbefolkningen främst genom födan. Analys av exponeringsbiomarkörer för BM i t ex urin ger ett tillförlitligt mått på den aktuella kroppsbelastningen och utgör ett gott komplement till andra sätt att uppskatta befolkningens exponering. Arbets- och miljömedicin och Avd för Arbets- och miljömedicin i Lund har med Naturvårdsverkets stöd tidigare undersökt halter av BM i dygns- alternativt morgonurin hos olika befolkningsgrupper i Skåne. Nu har rester av BM undersökts i morgonurinprov från 128 kvinnor (43-60 år) i Skåne. Medelålders kvinnor är en grupp som konsumerar förhållandevis mycket frukt och grönt, den livsmedelsgrupp som bidrar mest till exponeringen för BM. Deltagarna besvarade också enkäter med frågor om livsstil och fyllde i en matdagbok.Vi undersökte rester i urinen av fungiciderna mankozeb, prokloraz och tiabendazol, herbiciderna 2,4-diklorfenoxiättiksyra och 4-klor-2-metylfenoxiättiksyra, insekticiderna klorpyrifos och flera pyretroider samt retarderingsmedlen klormekvat och mepikvat. Analysmetodernas detektionsgränser var mellan 0,1 och 1,0 ng/mL.Samtliga biomarkörer kunde påvisas. Särskilt anmärkningsvärt var den utbredda exponeringen för retarderingsmedel, för mankozeb och klorpyrifos. Metaboliten TCP från klorpyrifos låg också förhållandevis högt i jämförelse med vuxna och barn i andra länder (USA, Costa Rica, Nicaragua). Vi fann högre halt av TCP hos vegetarianer.Olika biomarkörer för BM förekom i litet högre halter när kvinnorna konsumerat relativt mycket grönsaker, frukt/bär, spannmålsprodukter, salladsblad eller kaffe dagen innan urinprovet. Till exempel var resterna av tiabendazol högre hos de kvinnor som intagit citrusfrukter eller bananer dagen innan. Frukten behandlas i producentlandet med tiabendazol inför lagring och transport. Som vi sett i tidigare undersökta grupper var ETU-halterna i urinproven högre hos de som konsumerat vin före provet. Modersubstansen mankozeb används frekvent vid vinodling.De univariata jämförelserna mellan olika undergrupper ger indikationer på samband men djupare penetration av materialet behövs för säkra slutsatser. Med hänsyn till att många analyser gjorts finns också en risk för slumpmässiga fynd. Sammantaget utgör en biologisk övervakning som denna ändå en bas för fortsatt förståelse av bekämpningsmedlens roll för miljön och oss människor.
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| 7. |
- Mora, Ana M., et al.
(författare)
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Blood and hair manganese concentrations in pregnant women from the Infants' Environmental Health Study (ISA) in Costa Rica
- 2014
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 48:6, s. 3467-3476
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Tidskriftsartikel (refereegranskat)abstract
- Manganese (Mn), an essential nutrient, is a neurotoxicant at high concentrations. We measured Mn concentrations in repeated blood and hair samples collected from 449 pregnant women living near banana plantations with extensive aerial spraying of Mn-containing fungicide mancozeb in Costa Rica, and examined environmental and lifestyle factors associated with these biomarkers. Mean blood Mn and geometric mean hair Mn concentrations were 24.4 μg/L (8.9-56.3) and 1.8 μg/g (0.05-53.3), respectively. Blood Mn concentrations were positively associated with gestational age at sampling (β = 0.2; 95% CI: 0.1 to 0.2), number of household members (β = 0.4; 95% CI: 0.1 to 0.6), and living in a house made of permeable and difficult-to-clean materials (β = 2.6; 95% CI: 1.3 to 4.0); and inversely related to smoking (β = -3.1; 95% CI: -5.8 to -0.3). Hair Mn concentrations were inversely associated with gestational age at sampling (% change = 0.8; 95% CI: -1.6 to 0.0); and positively associated with living within 50 m of a plantation (% change = 42.1; 95% CI: 14.2 to 76.9) and Mn concentrations in drinking water (% change = 17.5; 95% CI: 12.2 to 22.8). Our findings suggest that pregnant women living near banana plantations aerially sprayed with mancozeb may be environmentally exposed to Mn.
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| 8. |
- Toft, Gunnar, et al.
(författare)
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Association between Pregnancy Loss and Urinary Phthalate Levels around the Time of Conception
- 2012
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Ingår i: Environmental Health Perspectives. - : Environmental Health Perspectives. - 1552-9924 .- 0091-6765. ; 120:3, s. 458-463
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Animal studies indicate that some phthalate metabolites may harm female reproductive function. OBJECTIVES: We assessed the associations between exposure to phthalate metabolites and pregnancy loss. METHODS: Using a previously established cohort of couples planning their first pregnancy, we analyzed four primary and two oxidized secondary phthalate metabolites in urine samples collected on day 10 after the first day of the last menstrual period before conception occurred (n = 128) and during the previous cycle (if any, is = 111). Subclinical embryonal loss was identified by repeated measurement of urinary human chorionic gonadotropin, and information on clinical spontaneous abortions was obtained by telephone interview with the mother. RESULTS: Pregnancy loss (n = 48) was increased among women with urinary concentration of monoethylhexyl phthalate (MEHP) in the upper tertile in the conception sample compared with women in the lowest tertile [adjusted odds ratio (OR) = 2.9; 95% confidence interval (CI): 1.1, 7.6]. The corresponding OR for subclinical embryonal loss (n = 32) was 40.7 (95% Cl: 4.5, 369.5). CONCLUSIONS: The phthalate metabolite MEHP was associated with higher occurrence of pregnancy loss. Because this is the first human study to show this association and the sample size is small, the findings need to be corroborated in independent studies.
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| 9. |
- Toft, G., et al.
(författare)
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Exposure to perfluorinated compounds and human semen quality in arctic and European populations
- 2012
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 27:8, s. 2532-2540
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Tidskriftsartikel (refereegranskat)abstract
- Perfluorinated compounds (PFCs) have been suspected to adversely affect human reproductive health. The aim of this study was to investigate the associations between PFC exposure and male semen quality. PFCs were measured in serum from 588 partners of pregnant women from Greenland, Poland and Ukraine who provided a semen sample, using liquid chromatography tandem mass spectrometry. Perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS) and perfluorononanoic acid (PFNA) could be detected in 97 of the samples. The associations between levels of these compounds and semen volume, sperm concentration, total sperm count, motility and morphology were assessed. Across countries, sperm concentration, total sperm count and semen volume were not consistently associated with PFOS, PFOA, PFHxS or PFNA levels. The proportion of morphologically normal cells was 35 lower [95 confidence interval (CI): 466) for the third tertile of PFOS exposure as compared with the first. A similar reduction was found in relation to increasing PFHxS levels. At the third PFOA exposure tertile, the percentage of motile spermatozoa was 19 (95 CI: 1 to 39) higher than in the first. The most robust finding in the present study was the negative associations between PFOS exposure and sperm morphology suggesting adverse effects of PFOS on semen quality, possibly due to interference with the endocrine activity or sperm membrane function. It cannot be excluded that this association and the positive association between PFOA and semen motility, which was not consistent across countries, might represent a chance finding due to the multiple statistical tests being performed.
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