umu.sePublications
Change search
Link to record
Permanent link

Direct link
BETA
Alternative names
Publications (10 of 22) Show all publications
Smith, T., Muller, D. C., Moons, K. G., Cross, A. J., Johansson, M., Ferrari, P., . . . Tzoulaki, I. (2018). Comparison of prognostic models to predict the occurrence of colorectal cancer in asymptomatic individuals: a systematic literature review and external validation in the EPIC and UK Biobank prospective cohort studies.. Gut, Article ID gutjnl-2017-315730.
Open this publication in new window or tab >>Comparison of prognostic models to predict the occurrence of colorectal cancer in asymptomatic individuals: a systematic literature review and external validation in the EPIC and UK Biobank prospective cohort studies.
Show others...
2018 (English)In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, article id gutjnl-2017-315730Article in journal (Refereed) Epub ahead of print
Abstract [en]

OBJECTIVE: To systematically identify and validate published colorectal cancer risk prediction models that do not require invasive testing in two large population-based prospective cohorts.

DESIGN: Models were identified through an update of a published systematic review and validated in the European Prospective Investigation into Cancer and Nutrition (EPIC) and the UK Biobank. The performance of the models to predict the occurrence of colorectal cancer within 5 or 10 years after study enrolment was assessed by discrimination (C-statistic) and calibration (plots of observed vs predicted probability).

RESULTS: The systematic review and its update identified 16 models from 8 publications (8 colorectal, 5 colon and 3 rectal). The number of participants included in each model validation ranged from 41 587 to 396 515, and the number of cases ranged from 115 to 1781. Eligible and ineligible participants across the models were largely comparable. Calibration of the models, where assessable, was very good and further improved by recalibration. The C-statistics of the models were largely similar between validation cohorts with the highest values achieved being 0.70 (95% CI 0.68 to 0.72) in the UK Biobank and 0.71 (95% CI 0.67 to 0.74) in EPIC.

CONCLUSION: Several of these non-invasive models exhibited good calibration and discrimination within both external validation populations and are therefore potentially suitable candidates for the facilitation of risk stratification in population-based colorectal screening programmes. Future work should both evaluate this potential, through modelling and impact studies, and ascertain if further enhancement in their performance can be obtained.

Keywords
cancer prevention, colorectal cancer, colorectal cancer screening, epidemiology, medical statistics
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-146375 (URN)10.1136/gutjnl-2017-315730 (DOI)29615487 (PubMedID)
Available from: 2018-04-06 Created: 2018-04-06 Last updated: 2018-06-09
Perrier, F., Novoloaca, A., Ambatipudi, S., Baglietto, L., Ghantous, A., Perduca, V., . . . Ferrari, P. (2018). Identifying and correcting epigenetics measurements for systematic sources of variation. Clinical Epigenetics, 10, Article ID 38.
Open this publication in new window or tab >>Identifying and correcting epigenetics measurements for systematic sources of variation
Show others...
2018 (English)In: Clinical Epigenetics, E-ISSN 1868-7083, Vol. 10, article id 38Article in journal (Refereed) Published
Abstract [en]

Background: Methylation measures quantified by microarray techniques can be affected by systematic variation due to the technical processing of samples, which may compromise the accuracy of the measurement process and contribute to bias the estimate of the association under investigation. The quantification of the contribution of the systematic source of variation is challenging in datasets characterized by hundreds of thousands of features.In this study, we introduce a method previously developed for the analysis of metabolomics data to evaluate the performance of existing normalizing techniques to correct for unwanted variation. Illumina Infinium HumanMethylation450K was used to acquire methylation levels in over 421,000 CpG sites for 902 study participants of a case-control study on breast cancer nested within the EPIC cohort. The principal component partial R-square (PC-PR2) analysis was used to identify and quantify the variability attributable to potential systematic sources of variation. Three correcting techniques, namely ComBat, surrogate variables analysis (SVA) and a linear regression model to compute residuals were applied. The impact of each correcting method on the association between smoking status and DNA methylation levels was evaluated, and results were compared with findings from a large meta-analysis.

Results:  A sizeable proportion of systematic variability due to variables expressing 'batch' and 'sample position' within 'chip' was identified, with values of the partial R-2 statistics equal to 9.5 and 11.4% of total variation, respectively. After application of ComBat or the residuals' methods, the contribution was 1.3 and 0.2%, respectively. The SVA technique resulted in a reduced variability due to 'batch' (1.3%) and 'sample position' (0.6%), and in a diminished variability attributable to 'chip' within a batch (0.9%). After ComBat or the residuals' corrections, a larger number of significant sites (k = 600 and k = 427, respectively) were associated to smoking status than the SVA correction (k = 96).

Conclusions: The three correction methods removed systematic variation in DNA methylation data, as assessed by the PC-PR2, which lent itself as a useful tool to explore variability in large dimension data. SVA produced more conservative findings than ComBat in the association between smoking and DNA methylation.

Place, publisher, year, edition, pages
London: BioMed Central, 2018
Keywords
Epigenetics, Methylation, Normalization, PC-PR2, Smoking status
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-146374 (URN)10.1186/s13148-018-0471-6 (DOI)000428271200001 ()29588806 (PubMedID)
Available from: 2018-04-06 Created: 2018-04-06 Last updated: 2018-08-07Bibliographically approved
Sundkvist, A., Myte, R., Palmqvist, R., Harlid, S. & van Guelpen, B. (2018). Plasma ghrelin is probably not a useful biomarker for risk prediction or early detection of colorectal cancer [Letter to the editor]. Gut
Open this publication in new window or tab >>Plasma ghrelin is probably not a useful biomarker for risk prediction or early detection of colorectal cancer
Show others...
2018 (English)In: Gut, ISSN 0017-5749, E-ISSN 1468-3288Article in journal, Letter (Refereed) Epub ahead of print
Keywords
cancer, colorectal cancer, epidemiology, gastrointestinal hormones
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-146376 (URN)10.1136/gutjnl-2018-316110 (DOI)29491131 (PubMedID)
Available from: 2018-04-06 Created: 2018-04-06 Last updated: 2018-08-10
Sundkvist, A., Myte, R., Bodén, S., Enroth, S., Gyllensten, U., Harlid, S. & van Guelpen, B. (2018). Targeted plasma proteomics identifies a novel, robust association between cornulin and Swedish moist snuff. Scientific Reports, 8(1), Article ID 2320.
Open this publication in new window or tab >>Targeted plasma proteomics identifies a novel, robust association between cornulin and Swedish moist snuff
Show others...
2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, no 1, article id 2320Article in journal (Refereed) Published
Abstract [en]

Lifestyle behaviors are believed to influence the body's inflammatory state. Chronic low-grade inflammation contributes to the development of major non-communicable diseases such as diabetes, cardiovascular disease and cancer. Inflammation may thus be an important link between lifestyle and disease. We evaluated self-reported physical activity, tobacco use and alcohol consumption in relation to plasma levels of 160 validated inflammatory and cancer biomarkers. The study included 138 participants from a population-based cohort, all with repeated sampling of plasma and data ten years apart, allowing consideration of both intra- and inter-individual variation. Of 17 relationships identified, the strongest was an independent, positive association between cornulin (CRNN) and Swedish moist snuff (snus) use. We replicated the finding in a second cohort of 501 individuals, in which a dose-response relationship was also observed. Snus explained approximately one fifth of the variance in CRNN levels in both sample sets (18% and 23%). In conclusion, we identified a novel, independent, dose-dependent association between CRNN and snus use. Further study is warranted, to evaluate the performance of CRNN as a potential snus biomarker. The putative importance of lifestyle behaviors on a wide range of protein biomarkers illustrates the need for more personalized biomarker cut-offs.

Place, publisher, year, edition, pages
London: Nature Publishing Group, 2018
National Category
Public Health, Global Health, Social Medicine and Epidemiology Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-145046 (URN)10.1038/s41598-018-20794-3 (DOI)29396534 (PubMedID)
Available from: 2018-02-19 Created: 2018-02-19 Last updated: 2018-06-09Bibliographically approved
Wilson, L. E., Harlid, S., Xu, Z., Sandler, D. P. & Taylor, J. A. (2017). An epigenome-wide study of body mass index and DNA methylation in blood using participants from the Sister Study cohort. International Journal of Obesity, 41(1), 194-199
Open this publication in new window or tab >>An epigenome-wide study of body mass index and DNA methylation in blood using participants from the Sister Study cohort
Show others...
2017 (English)In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 41, no 1, p. 194-199Article in journal (Refereed) Published
Abstract [en]

BACKGROUND/OBJECTIVES: The relationship between obesity and chronic disease risk is well-established; the underlying biological mechanisms driving this risk increase may include obesity-related epigenetic modifications. To explore this hypothesis, we conducted a genome-wide analysis of DNA methylation and body mass index (BMI) using data from a subset of women in the Sister Study.

SUBJECTS/METHODS: The Sister Study is a cohort of 50 884 US women who had a sister with breast cancer but were free of breast cancer themselves at enrollment. Study participants completed examinations which included measurements of height and weight, and provided blood samples. Blood DNA methylation data generated with the Illumina Infinium HumanMethylation27 BeadChip array covering 27,589 CpG sites was available for 871 women from a prior study of breast cancer and DNA methylation. To identify differentially methylated CpG sites associated with BMI, we analyzed this methylation data using robust linear regression with adjustment for age and case status. For those CpGs passing the false discovery rate significance level, we examined the association in a replication set comprised of a non-overlapping group of 187 women from the Sister Study who had DNA methylation data generated using the Infinium HumanMethylation450 BeadChip array. Analysis of this expanded 450 K array identified additional BMI-associated sites which were investigated with targeted pyrosequencing.

RESULTS: Four CpG sites reached genome-wide significance (false discovery rate (FDR) q<0.05) in the discovery set and associations for all four were significant at strict Bonferroni correction in the replication set. An additional 23 sites passed FDR in the replication set and five were replicated by pyrosequencing in the discovery set. Several of the genes identified including ANGPT4, RORC, SOCS3, FSD2, XYLT1, ABCG1, STK39, ASB2 and CRHR2 have been linked to obesity and obesity-related chronic diseases.

CONCLUSIONS: Our findings support the hypothesis that obesity-related epigenetic differences are detectable in blood and may be related to risk of chronic disease.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-132605 (URN)10.1038/ijo.2016.184 (DOI)000394143100026 ()27773939 (PubMedID)
Available from: 2017-03-17 Created: 2017-03-17 Last updated: 2018-06-09Bibliographically approved
Harlid, S., Myte, R. & Van Guelpen, B. (2017). Replication of Epigenome-wide Associations Related to Body Mass Index Using the Infinium MethylationEPIC BeadChip on Repeated Samples. Paper presented at Annual Meeting of the International-Genetic-Epidemiology-Society (IGES), SEP 09-11, 2017, Queens Coll, Cambridge, ENGLAND. Genetic Epidemiology, 41(7), 680-680
Open this publication in new window or tab >>Replication of Epigenome-wide Associations Related to Body Mass Index Using the Infinium MethylationEPIC BeadChip on Repeated Samples
2017 (English)In: Genetic Epidemiology, ISSN 0741-0395, E-ISSN 1098-2272, Vol. 41, no 7, p. 680-680Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
John Wiley & Sons, 2017
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-141468 (URN)000413035000103 ()
Conference
Annual Meeting of the International-Genetic-Epidemiology-Society (IGES), SEP 09-11, 2017, Queens Coll, Cambridge, ENGLAND
Note

Meeting Abstract: 101

Available from: 2017-11-21 Created: 2017-11-21 Last updated: 2018-06-09Bibliographically approved
Harlid, S., Adgent, M., Jefferson, W. N., Panduri, V., Umbach, D. M., Xu, Z., . . . Taylor, J. A. (2017). Soy formula and epigenetic modifications: analysis of vaginal epithelial cells from infant girls in the IFED study. Journal of Environmental Health Perspectives, 125(3), 447-452
Open this publication in new window or tab >>Soy formula and epigenetic modifications: analysis of vaginal epithelial cells from infant girls in the IFED study
Show others...
2017 (English)In: Journal of Environmental Health Perspectives, ISSN 0091-6765, E-ISSN 1552-9924, Vol. 125, no 3, p. 447-452Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Early-life exposure to estrogenic compounds affects the development of the reproductive system in rodent models and humans. Soy products, which contain phytoestrogens such as genistein, are one source of exposure in infants fed soy formula, and they result in high serum concentrations.

OBJECTIVES: Our goal was to determine whether soy exposure is associated with differential DNA methylation in vaginal cells from soy-fed infant girls.

METHODS: Using the Illumina HumanMethylation450 BeadChip, we evaluated epigenome-wide DNA methylation in vaginal cells from four soy formula-fed and six cow formula-fed girls from the Infant Feeding and Early Development (IFED) study. Using pyrosequencing we followed up the two most differentially methylated sites in 214 vaginal cell samples serially collected between birth and 9 months of age from 50 girls (28 soy formula-fed and 22 cow formula-fed). With a mouse model, we examined the effect of neonatal exposure to genistein on gene specific mRNA levels in vaginal tissue.

RESULTS: The epigenome-wide scan suggested differences in methylation between soy formula-fed and cow formula-fed infants at three CpGs in the gene proline rich 5 like (PRR5L) (p < 10(4)). Pyrosequencing of the two feeding groups found that methylation levels progressively diverged with age, with pointwise differences becoming statistically significant after 126 days. Genistein-exposed mice showed a 50% decrease in vaginal Prr5l mRNA levels compared to controls.

CONCLUSIONS: Girls fed soy formula have altered DNA methylation in vaginal cell DNA which may be associated with decreased expression of an estrogen-responsive gene.

National Category
Pharmacology and Toxicology Occupational Health and Environmental Health
Identifiers
urn:nbn:se:umu:diva-132604 (URN)10.1289/EHP428 (DOI)000395714400027 ()27539829 (PubMedID)
Available from: 2017-03-17 Created: 2017-03-17 Last updated: 2018-06-09Bibliographically approved
Harlid, S., Myte, R. & Van Guelpen, B. (2017). The metabolic syndrome, inflammation, and colorectal cancer risk: an evaluation of large panels of plasma protein markers using erepeated, prediagnostic samples. Mediators of Inflammation, Article ID 4803156.
Open this publication in new window or tab >>The metabolic syndrome, inflammation, and colorectal cancer risk: an evaluation of large panels of plasma protein markers using erepeated, prediagnostic samples
2017 (English)In: Mediators of Inflammation, ISSN 0962-9351, E-ISSN 1466-1861, article id 4803156Article in journal (Refereed) Published
Abstract [en]

Metabolic syndrome (MetS), a set of metabolic risk factors including obesity, dysglycemia, and dyslipidemia, is associated with increased colorectal cancer (CRC) risk. A putative biological mechanism is chronic, low-grade inflammation, both a feature of MetS and a CRC risk factor. However, excess body fat also induces a proinflammatory state and increases CRC risk. In order to explore the relationship between MetS, body size, inflammation, and CRC, we studied large panels of inflammatory and cancer biomarkers. We included 138 participants from the Vasterbotten Intervention Programme with repeated sampling occasions, 10 years apart. Plasma samples were analyzed for 178 protein markers by proximity extension assay. To identify associations between plasma protein levels and MetS components, linear mixed models were fitted for each protein. Twelve proteins were associated with at least one MetS component, six of which were associated with MetS score. MetS alone was not related to any protein. Instead, BMI displayed by far the strongest associations with the biomarkers. One of the 12 MetS score-related proteins (FGF-21), also associated with BMI, was associated with an increased CRC risk (OR 1.71, 95% CI 1.19-2.47). We conclude that overweight and obesity, acting through both inflammation and other mechanisms, likely explain the MetS-CRC connection.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-133677 (URN)10.1155/2017/4803156 (DOI)000397878000001 ()
Available from: 2017-04-20 Created: 2017-04-20 Last updated: 2018-06-09Bibliographically approved
Harlid, S., Myte, R. & van Guelpen, B. (2017). The metabolic syndrome, inflammation and colorectal cancer risk: an evaluation of large panels of plasma protein markers using repeated, pre-diagnostic samples. Mediators of Inflammation, Article ID 4803156.
Open this publication in new window or tab >>The metabolic syndrome, inflammation and colorectal cancer risk: an evaluation of large panels of plasma protein markers using repeated, pre-diagnostic samples
2017 (English)In: Mediators of Inflammation, article id 4803156Article in journal (Refereed) Published
Abstract [en]

Metabolic syndrome (MetS), a set of metabolic risk factors including obesity, dysglycemia, and dyslipidemia, is associated with increased colorectal cancer (CRC) risk. A putative biological mechanism is chronic, low-grade inflammation, both a feature of MetS and a CRC risk factor. However, excess body fat also induces a proinflammatory state and increases CRC risk. In order to explore the relationship between MetS, body size, inflammation, and CRC, we studied large panels of inflammatory and cancer biomarkers. We included 138 participants from the Västerbotten Intervention Programme with repeated sampling occasions, 10 years apart. Plasma samples were analyzed for 178 protein markers by proximity extension assay. To identify associations between plasma protein levels and MetS components, linear mixed models were fitted for each protein. Twelve proteins were associated with at least one MetS component, six of which were associated with MetS score. MetS alone was not related to any protein. Instead, BMI displayed by far the strongest associations with the biomarkers. One of the 12 MetS score-related proteins (FGF-21), also associated with BMI, was associated with an increased CRC risk (OR 1.71, 95% CI 1.19–2.47). We conclude that overweight and obesity, acting through both inflammation and other mechanisms, likely explain the MetS-CRC connection.

Place, publisher, year, edition, pages
Hindawi Publishing Corporation, 2017
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-134167 (URN)10.1155/2017/4803156 (DOI)
Funder
Swedish Society of MedicineSwedish Cancer SocietyVästerbotten County Council
Available from: 2018-02-19 Created: 2018-02-19 Last updated: 2018-10-15Bibliographically approved
Markunas, C. A., Wilcox, A. J., Xu, Z., Joubert, B. R., Harlid, S., Panduri, V., . . . Taylor, J. A. (2016). Maternal Age at Delivery Is Associated with an Epigenetic Signature in Both Newborns and Adults. PLoS ONE, 11(7), Article ID e0156361.
Open this publication in new window or tab >>Maternal Age at Delivery Is Associated with an Epigenetic Signature in Both Newborns and Adults
Show others...
2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 7, article id e0156361Article in journal (Refereed) Published
Abstract [en]

Offspring of older mothers are at increased risk of adverse birth outcomes, childhood cancers, type 1 diabetes, and neurodevelopmental disorders. The underlying biologic mechanisms for most of these associations remain obscure. One possibility is that maternal aging may produce lasting changes in the epigenetic features of a child's DNA. To test this, we explored the association of mothers' age at pregnancy with methylation in her offspring, using blood samples from 890 Norwegian newborns and measuring DNA methylation at more than 450,000 CpG sites across the genome. We examined replication of a maternal-age finding in an independent group of 1062 Norwegian newborns, and then in 200 US middle-aged women. Older maternal age was significantly associated with reduced methylation at four adjacent CpGs near the 2nd exon of KLHL35 in newborns (p-values ranging from 3x10-6 to 8x10-7). These associations were replicated in the independent set of newborns, and replicated again in women 40 to 60 years after their birth. This study provides the first example of parental age permanently affecting the epigenetic profile of offspring. While the specific functions of the affected gene are unknown, this finding opens the possibility that a mother's age at pregnancy could affect her child's health through epigenetic mechanisms.

National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-132603 (URN)10.1371/journal.pone.0156361 (DOI)27383059 (PubMedID)
Available from: 2017-03-17 Created: 2017-03-17 Last updated: 2018-06-09Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-8540-6891

Search in DiVA

Show all publications