Northern Finland Laboratory Center NordLab

Oulu, Finland

Northern Finland Laboratory Center NordLab

Oulu, Finland
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Mendola P.,National Health Research Institute | Wallace M.,National Health Research Institute | Liu D.,National Health Research Institute | Robledo C.,National Health Research Institute | And 5 more authors.
Environmental Research | Year: 2016

Maternal asthma and air pollutants have been independently associated with preeclampsia but rarely studied together. Our objective was to comprehensively evaluate preeclampsia risk based on the interaction of maternal asthma and air pollutants. Preeclampsia and asthma diagnoses, demographic and clinical data came from electronic medical records for 210,508 singleton deliveries. Modified Community Multiscale Air Quality models estimated preconception, first and second trimester and whole pregnancy exposure to: particulate matter (PM)<2.5 and <10 µm, ozone, nitrogen oxides (NOx), sulfur dioxide (SO2) and carbon monoxide (CO); PM2.5 constituents; volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs). Asthma-pollutant interaction adjusted relative risks (RR) and 95% confidence intervals (CI) for preeclampsia were calculated by interquartile range for criteria pollutants and high exposure (≥75th percentile) for PAHs and VOCs. Asthmatics had higher risk associated with first trimester NOx and SO2 and whole pregnancy elemental carbon (EC) exposure than non-asthmatics, but only EC significantly increased risk (RR=1.11, CI:1.03–1.21). Asthmatics also had a 10% increased risk associated with second trimester CO. Significant interactions were observed for nearly all VOCs and asthmatics had higher risk during all time windows for benzene, ethylbenzene, m-xylene, o-xylene, p-xylene and toluene while most PAHs did not increase risk. © 2016

Mannisto T.,Northern Finland Laboratory Center NordLab | Mannisto T.,University of Oulu | Mannisto T.,Finnish National Institute for Health and Welfare | Sherman S.,The Emmes Corporation | Ying Q.,Texas A&M University
Annals of Epidemiology | Year: 2017

Purpose In this case-crossover study, we investigated the odds of having a labor/delivery with cardiovascular event (i.e., ischemic heart disease, stroke, heart failure, cardiac arrest/failure, and other or unspecified cardiovascular events) associated with acute exposure to common air pollutants. Methods We selected 680 women with singleton pregnancy and cardiovascular events at labor/delivery from 12 U.S. clinical sites (2002–2008). Exposures to six criteria air pollutants, six particulate constituents, and 26 air toxics were obtained using modified Community Multiscale Air Quality models. Conditional logistic regression models calculated the odds ratio (OR) and 95% confidence intervals (CI) comparing exposures during the day of delivery, the week before delivery, and each of the days of the week before delivery to two control periods before and after. Results An interquartile range increase in particulate matter (PM) ≤2.5 microns and nitric oxide exposures during the week before delivery was associated with an 11% (OR 1.11, 95% CI: 1.01–1.23) and 21% (OR 1.21, 95% CI: 1.04–1.42) increased cardiovascular events odds, respectively. These pollutants, sulfur dioxide, carbon monoxide, PM ≤ 10 microns, and some PM constituents showed associations with event odds for days 0, 1, 5, and 6 before delivery. Inverse associations were observed for O3 and some PM constituents as well as air toxics. Conclusions Cardiovascular events at labor/delivery merit more attention in relation to air pollution. © 2017

Ikaheimo T.M.,University of Oulu | Jaakkola K.,University of Oulu | Jaakkola K.,Finnish Defence Forces | Jokelainen J.,University of Oulu | And 6 more authors.
Viruses | Year: 2016

Both temperature and humidity may independently or jointly contribute to the risk of human rhinovirus (HRV) infections, either through altered survival and spread of viruses in the environment or due to changes in host susceptibility. This study examined the relationship between short-term variations in temperature and humidity and the risk of HRV infections in a subarctic climate. We conducted a case-crossover study among conscripts (n = 892) seeking medical attention due to respiratory symptoms during their military training and identified 147 HRV cases by real-time PCR. An average temperature, a decline in daily ambient temperature and absolute humidity (AH) during the three preceding days of the onset (hazard period) and two reference periods (a week prior and after the onset) were obtained. The average daily temperature preceding HRV infections was –9.9 ± 4.9 °C and the average AH was 2.2 ± 0.9 g/m3. An average (odds ratios (OR) 1.07 (95% confidence interval (CI) 1.00–1.15)) and maximal (OR 1.08 (1.01–1.17)) change in temperature increased the risk of HRV infections by 8% per 1 _C decrease. An average (OR 1.20 (CI 1.03–1.40)) and maximal decrease (OR 1.13 (CI 0.96–1.34)) in AH increased the risk of HRV infection by 13% and 20% per 0.5 g/m3 decrease. A higher average temperature during the three preceding days was positively associated with HRV infections (OR 1.07 (CI 1.00–1.15)). A decrease rather than low temperature and humidity per se during the preceding few days increases the risk of HRV infections in a cold climate. The information is applicable to populations residing in cold climates for appropriate personal protection and prevention of adverse health effects. © 2016 by the authors; licensee MDPI, Basel, Switzerland.

Mantere T.,University of Oulu | Mantere T.,Northern Finland Laboratory Center NordLab | Haanpaa M.,University of Oulu | Haanpaa M.,Northern Finland Laboratory Center NordLab | And 21 more authors.
Clinical Genetics | Year: 2015

Mutations in downstream Fanconi anemia (FA) pathway genes, BRCA2, PALB2, BRIP1 and RAD51C, explain part of the hereditary breast cancer susceptibility, but the contribution of other FA genes has remained questionable. Due to FA's rarity, the finding of recurrent deleterious FA mutations among breast cancer families is challenging. The use of founder populations, such as the Finns, could provide some advantage in this. Here, we have resolved complementation groups and causative mutations of five FA patients, representing the first mutation confirmed FA cases in Finland. These patients belonged to complementation groups FA-A (n=3), FA-G (n=1) and FA-I (n=1). The prevalence of the six FA causing mutations was then studied in breast (n=1840) and prostate (n=565) cancer cohorts, and in matched controls (n=1176 females, n=469 males). All mutations were recurrent, but no significant association with cancer susceptibility was observed for any: the prevalence of FANCI c.2957_2969del and c.3041G>A mutations was even highest in healthy males (1.7%). This strengthens the exclusive role of downstream genes in cancer predisposition. From a clinical point of view, current results provide fundamental information of the mutations to be tested first in all suspected FA cases in Finland. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd 88 1 July 2015 10.1111/cge.12447 SHORT REPORT SHORT REPORTS © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

PubMed | Hannover Medical School, Pomeranian Medical University, Finnish Institute of Occupational Health, Copenhagen University and 12 more.
Type: Journal Article | Journal: Breast cancer research : BCR | Year: 2016

P.I157T is a CHEK2 missense mutation associated with a modest increase in breast cancer risk. Previously, another CHEK2 mutation, the protein truncating c.1100delC has been associated with poor prognosis of breast cancer patients. Here, we have investigated patient survival and characteristics of breast tumors of germ line p.I157T carriers.We included in the analyses 26,801 European female breast cancer patients from 15 studies participating in the Breast Cancer Association Consortium. We analyzed the association between p.I157T and the clinico-pathological breast cancer characteristics by comparing the p.I157T carrier tumors to non-carrier and c.1100delC carrier tumors. Similarly, we investigated the p.I157T associated risk of early death, breast cancer-associated death, distant metastasis, locoregional relapse and second breast cancer using Cox proportional hazards models. Additionally, we explored the p.I157T-associated genomic gene expression profile using data from breast tumors of 183 Finnish female breast cancer patients (ten p.I157T carriers) (GEO: GSE24450). Differential gene expression analysis was performed using a moderated t test. Functional enrichment was investigated using the DAVID functional annotation tool and gene set enrichment analysis (GSEA). The tumors were classified into molecular subtypes according to the St Gallen 2013 criteria and the PAM50 gene expression signature.P.I157T was not associated with increased risk of early death, breast cancer-associated death or distant metastasis relapse, and there was a significant difference in prognosis associated with the two CHEK2 mutations, p.I157T and c.1100delC. Furthermore, p.I157T was associated with lobular histological type and clinico-pathological markers of good prognosis, such as ER and PR expression, low TP53 expression and low grade. Gene expression analysis suggested luminal A to be the most common subtype for p.I157T carriers and CDH1 (cadherin 1) target genes to be significantly enriched among genes, whose expression differed between p.I157T and non-carrier tumors.Our analyses suggest that there are fundamental differences in breast tumors of CHEK2:p.I157T and c.1100delC carriers. The poor prognosis associated with c.1100delC cannot be generalized to other CHEK2 mutations.

PubMed | Karolinska Institutet, University of Cologne, Instituto Oncologico Veneto Iov Irccs Instituto Of Ricovero E Cura A Carattere Scientifico, Rutgers Cancer Institute of New Jersey and 126 more.
Type: | Journal: Nature communications | Year: 2016

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 10(-20)), ER-negative BC (P=1.1 10(-13)), BRCA1-associated BC (P=7.7 10(-16)) and triple negative BC (P-diff=2 10(-5)). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 10(-3)) and ABHD8 (P<2 10(-3)). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.

Komulainen-Ebrahim J.,University of Oulu | Saastamoinen E.,University of Oulu | Rahikkala E.,University of Oulu | Helander H.,University of Oulu | And 5 more authors.
Neuropediatrics | Year: 2017

Background Methionine synthase deficiency is a rare inborn error of intracellular cobalamin metabolism caused by mutations in the MTR (5-methyltetrahydrofolate-homocysteine S-methyltransferase) gene, resulting in megaloblastic anemia and neurologic symptoms. Methods and Results We describe for the first time a homozygous MTR gene c.3518C > T (p.P1173L) mutation in a patient with severe megaloblastic anemia, developmental delay, and drug-resistant seizures associated with hyperhomocysteinemia and hypomethioninemia. Methionine synthase activity was only 9% of the reference value, and MTR protein expression was decreased in the fibroblasts of the patient. The clinical features of our patient are similar to previously published patients with the complementation type G disorder of methionine synthase deficiency with the exception of drug-resistant seizures. However, intramuscular injections of hydroxocobalamin (OHCbl) in conjunction with betaine and folic acid provided verified clinical and electrophysiological treatment response. Conclusion This study emphasizes the importance of early diagnosis of patients having neurologic symptoms due to methionine synthase deficiency where early treatment has significant effects on the clinical outcome of the patients. Elevated level of plasma homocysteine together with low methionine in plasma amino acid analysis should raise a suspicion of remethylation disorder. Copyright © 2017, Georg Thieme Verlag KG. All rights reserved.

Mendola P.,National Health Research Institute | Wallace M.,National Health Research Institute | Hwang B.S.,National Health Research Institute | Liu D.,National Health Research Institute | And 8 more authors.
Journal of Allergy and Clinical Immunology | Year: 2016

Background: Ambient air pollutants may increase preterm birth (PTB) risk, but critical exposure windows are uncertain. The interaction of asthma and pollutant exposure is rarely studied. Objective: We sought to assess the interaction of maternal asthma and air pollutant exposures in relation to PTB risk. Methods: Electronic medical records for 223,502 US deliveries were linked with modified Community Multiscale Air Quality model outputs. Logistic regression with generalized estimating equations estimated the odds ratio and 95% CIs for PTB on the basis of the interaction of maternal asthma and particulate matter with aerodynamic diameter of less than 2.5 microns and particulate matter with aerodynamic diameter of less than 10 microns, ozone (O3), nitrogen oxides (NOx), sulfur dioxide (SO2), and carbon monoxide (CO) per interquartile range. For each gestational week 23 to 36, exposures among women who delivered were compared with those remaining pregnant. Three-month preconception, whole pregnancy, weeks 1 to 28, and the last 6 weeks of gestation averages were also evaluated. Results: On assessing PTB by gestational week, we found that significant asthma interactions were sporadic before 30 weeks but more common during weeks 34 to 36, with higher risk among mothers with asthma for NOx, CO, and SO2 exposure and an inverse association with O3 in week 34. Odds of PTB were significantly higher among women with asthma for CO and NOx exposure preconception and early in pregnancy. In the last 6 weeks of pregnancy, PTB risk associated with particulate matter with aerodynamic diameter of less than 10 microns was higher among women with asthma. Conclusions: Mothers with asthma may experience a higher risk for PTB after exposure to traffic-related pollutants such as CO and NOx, particularly for exposures 3-months preconception and in the early weeks of pregnancy. © 2016.

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