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- Cajuso, T, et al.
(author)
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Retrotransposon insertions can initiate colorectal cancer and are associated with poor survival
- 2019
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4022-
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Journal article (peer-reviewed)abstract
- Genomic instability pathways in colorectal cancer (CRC) have been extensively studied, but the role of retrotransposition in colorectal carcinogenesis remains poorly understood. Although retrotransposons are usually repressed, they become active in several human cancers, in particular those of the gastrointestinal tract. Here we characterize retrotransposon insertions in 202 colorectal tumor whole genomes and investigate their associations with molecular and clinical characteristics. We find highly variable retrotransposon activity among tumors and identify recurrent insertions in 15 known cancer genes. In approximately 1% of the cases we identify insertions in APC, likely to be tumor-initiating events. Insertions are positively associated with the CpG island methylator phenotype and the genomic fraction of allelic imbalance. Clinically, high number of insertions is independently associated with poor disease-specific survival.
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- Kemppainen, Nina, et al.
(author)
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Brain amyloid load and its associations with cognition and vascular risk factors in FINGER Study
- 2018
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In: Neurology. - 0028-3878 .- 1526-632X. ; 90:3, s. E206-E213
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Journal article (peer-reviewed)abstract
- Objective To investigate brain amyloid pathology in a dementia-risk population defined as cardiovascular risk factors, aging, and dementia risk (CAIDE) score of at least 6 but with normal cognition and to examine associations between brain amyloid load and cognitive performance and vascular risk factors.Methods A subgroup of 48 individuals from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) main study participated in brain C-11-Pittsburgh compound B (PiB)-PET imaging, brain MRI, and neuropsychological assessment at the beginning of the study. Lifestyle/vascular risk factors were determined as body mass index, blood pressure, total and low-density lipoprotein cholesterol, and glucose homeostasis model assessment. White matter lesions were visually rated from MRIs by a semiquantitative Fazekas score.Results Twenty participants (42%) had a positive PiB-PET on visual analysis. The PiB-positive group performed worse in executive functioning tests, included more participants with APOE epsilon 4 allele (50%), and showed slightly better glucose homeostasis compared to PiB-negative participants. PiB-positive and -negative participants did not differ significantly in other cognitive domain scores or other vascular risk factors. There was no significant difference in Fazekas score between the PiB groups.Conclusions The high percentage of PiB-positive participants provides evidence of a successful recruitment process of the at-risk population in the main FINGER intervention trial. The results suggest a possible association between early brain amyloid accumulation and decline in executive functions. APOE epsilon 4 was clearly associated with amyloid positivity, but no other risk factor was found to be associated with positive PiB-PET.
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- Morawska, L., et al.
(author)
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Indoor aerosols: from personal exposure to risk assessment
- 2013
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In: Indoor Air. - : Hindawi Limited. - 0905-6947. ; 23:6, s. 462-487
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Research review (peer-reviewed)abstract
- Motivated by growing considerations of the scale, severity, and risks associated with human exposure to indoor particulate matter, this work reviewed existing literature to: (i) identify state-of-the-art experimental techniques used for personal exposure assessment; (ii) compare exposure levels reported for domestic/school settings in different countries (excluding exposure to environmental tobacco smoke and particulate matter from biomass cooking in developing countries); (iii) assess the contribution of outdoor background vs indoor sources to personal exposure; and (iv) examine scientific understanding of the risks posed by personal exposure to indoor aerosols. Limited studies assessing integrated daily residential exposure to just one particle size fraction, ultrafine particles, show that the contribution of indoor sources ranged from 19% to 76%. This indicates a strong dependence on resident activities, source events and site specificity, and highlights the importance of indoor sources for total personal exposure. Further, it was assessed that 10-30% of the total burden of disease from particulate matter exposure was due to indoor-generated particles, signifying that indoor environments are likely to be a dominant environmental factor affecting human health. However, due to challenges associated with conducting epidemiological assessments, the role of indoor-generated particles has not been fully acknowledged, and improved exposure/risk assessment methods are still needed, together with a serious focus on exposure control.
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- Palin, K, et al.
(author)
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Contribution of allelic imbalance to colorectal cancer
- 2018
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 3664-
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Journal article (peer-reviewed)abstract
- Point mutations in cancer have been extensively studied but chromosomal gains and losses have been more challenging to interpret due to their unspecific nature. Here we examine high-resolution allelic imbalance (AI) landscape in 1699 colorectal cancers, 256 of which have been whole-genome sequenced (WGSed). The imbalances pinpoint 38 genes as plausible AI targets based on previous knowledge. Unbiased CRISPR-Cas9 knockout and activation screens identified in total 79 genes within AI peaks regulating cell growth. Genetic and functional data implicate loss of TP53 as a sufficient driver of AI. The WGS highlights an influence of copy number aberrations on the rate of detected somatic point mutations. Importantly, the data reveal several associations between AI target genes, suggesting a role for a network of lineage-determining transcription factors in colorectal tumorigenesis. Overall, the results unravel the contribution of AI in colorectal cancer and provide a plausible explanation why so few genes are commonly affected by point mutations in cancers.
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- Rumrich, I, et al.
(author)
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Effects of maternal smoking on body size and proportions at birth: a register-based cohort study of 1.4 million births
- 2020
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In: BMJ open. - : BMJ. - 2044-6055. ; 10:2, s. e033465-
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Journal article (peer-reviewed)abstract
- The aim of our work was to analyse the effect of maternal smoking on body size and body proportions of newborns when the mother had smoked only during the first trimester, in comparison with continued smoking after the first trimester. Furthermore, we have evaluated how growth restriction associated with maternal smoking contributes to changes in body proportions.DesignRegister-based cohort studySettingMaternal Exposure (MATEX) cohort identified from the Finnish Medical Birth Register.ParticipantsSingleton births without congenital anomalies and missing data (1.38 million) from 1 January 1991 to 31 December 2016.MethodsLogistic regression was used to quantify the effect of maternal smoking, stratified by the maternal smoking status.Outcome measuresBody proportions indicated by low brain-to-body ratio (defined as <10th percentile); high ponderal index and high head-to-length ratio (defined as >90th percentile); small body size for gestational age at birth (defined as weight, length or head circumference <10th percentile) and preterm birth (<37 weeks) and low birth weight (2500 g).ResultsContinued smoking after the first trimester was associated with high ponderal index (OR 1.26, 95% CI 1.23 to 1.28), low brain-to-body ratio (1.11, 1.07–1.15) and high head-to-length ratio (1.22, 1.19–1.26), corresponding with absolute risks of 22%, 10% and 19%, respectively). The effects were slightly lower when smoking had been quit during the first trimester. Similar effects were seen for the body size variables and low birth weight. Preterm birth was not associated with smoking only during first trimester.ConclusionsMaternal smoking, independent of smoking duration during pregnancy, was associated with abnormal body proportions resulting from larger reduction of length and head circumference in comparison to weight. The effects of having quit smoking during the first trimester and having continued smoking after the first trimester were similar, suggesting the importance of early pregnancy as a sensitive exposure window.
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- Rumrich, IK, et al.
(author)
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Smoking during pregnancy in Finland - Trends in the MATEX cohort
- 2019
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In: Scandinavian journal of public health. - : SAGE Publications. - 1651-1905 .- 1403-4948. ; 47:8, s. 890-898
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Journal article (peer-reviewed)abstract
- Aims: In Finland, smoking rates in the general population are decreasing due to increased awareness of the adverse effects and tightened tobacco legislation. However, previous studies have shown that smoking in pregnant Finnish women remained as high as in the general Finnish female population at around 15% in 2010. Our aim was to describe temporal and spatial trends in smoking behaviour, and determinants of changes in smoking behaviour between first and second pregnancy. Methods: Self-reported smoking from the Finnish Medical Birth Register covered the years 1991–2015 ( N=1,435,009). The association of maternal age and socioeconomic status with smoking rate was analysed. Spatial trends were assessed at municipality level. Results: The overall smoking rate during early pregnancy remained fairly stable at around 15% from 1991 to 2015, but increased in teenage and young women below 25 years of age. The mean smoking rate (36%) was higher in these age groups than in older pregnant women (11%). Through the study period the smoking rate remained higher in blue collar workers compared with higher socioeconomic groups. Between the first and second child, on average only 4% of women started to smoke and 41% quitted. Smoking rates developed less favourably in Eastern Finland. Conclusions: The observed increase in smoking rate during pregnancy in teenage and young women is concerning. Pregnancy is a trigger point for smoking cessation in a big fraction of pregnant women. More studies are needed to explain the opposite trends of smoking rates in Northern and Western Finland compared with Eastern Finland.
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- Tanja, S, et al.
(author)
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Air temperature triggers the recovery of evergreen boreal forest photosynthesis in spring
- 2003
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In: Global Change Biology. - : Wiley. - 1354-1013. ; 9:10, s. 1410-1426
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Journal article (peer-reviewed)abstract
- The timing of the commencement of photosynthesis (P-*) in spring is an important determinant of growing-season length and thus of the productivity of boreal forests. Although controlled experiments have shed light on environmental mechanisms triggering release from photoinhibition after winter, quantitative research for trees growing naturally in the field is scarce. In this study, we investigated the environmental cues initiating the spring recovery of boreal coniferous forest ecosystems under field conditions. We used meteorological data and above-canopy eddy covariance measurements of the net ecosystem CO2 exchange (NEE) from five field stations located in northern and southern Finland, northern and southern Sweden, and central Siberia. The within- and intersite variability for P-* was large, 30-60 days. Of the different climate variables examined, air temperature emerged as the best predictor for P-* in spring. We also found that 'soil thaw', defined as the time when near-surface soil temperature rapidly increases above 0degreesC, is not a useful criterion for P-*. In one case, photosynthesis commenced 1.5 months before soil temperatures increased significantly above 0degreesC. At most sites, we were able to determine a threshold for air-temperature-related variables, the exceeding of which was required for P-*. A 5-day running-average temperature (T-5) produced the best predictions, but a developmental-stage model (S) utilizing a modified temperature sum concept also worked well. But for both T-5 and S, the threshold values varied from site to site, perhaps reflecting genetic differences among the stands or climate-induced differences in the physiological state of trees in late winter/early spring. Only at the warmest site, in southern Sweden, could we obtain no threshold values for T-5 or S that could predict P-* reliably. This suggests that although air temperature appears to be a good predictor for P-* at high latitudes, there may be no unifying ecophysiological relationship applicable across the entire boreal zone.
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