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BETA
van Guelpen, BethanyORCID iD iconorcid.org/0000-0002-9692-101x
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Publications (10 of 84) Show all publications
Mullee, A., Romaguera, D., Pearson-Stuttard, J., Viallon, V., Stepien, M., Freisling, H., . . . Murphy, N. (2019). Association Between Soft Drink Consumption and Mortality in 10 European Countries. JAMA Internal Medicine
Open this publication in new window or tab >>Association Between Soft Drink Consumption and Mortality in 10 European Countries
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2019 (English)In: JAMA Internal Medicine, ISSN 2168-6106, E-ISSN 2168-6114Article in journal (Refereed) Epub ahead of print
Abstract [en]

Importance: Soft drinks are frequently consumed, but whether this consumption is associated with mortality risk is unknown and has been understudied in European populations to date.

Objective: To examine the association between total, sugar-sweetened, and artificially sweetened soft drink consumption and subsequent total and cause-specific mortality.

Design, Setting, and Participants: This population-based cohort study involved participants (n = 451 743 of the full cohort) in the European Prospective Investigation into Cancer and Nutrition (EPIC), an ongoing, large multinational cohort of people from 10 European countries (Denmark, France, Germany, Greece, Italy, the Netherlands, Norway, Spain, Sweden, and the United Kingdom), with participants recruited between January 1, 1992, and December 31, 2000. Excluded participants were those who reported cancer, heart disease, stroke, or diabetes at baseline; those with implausible dietary intake data; and those with missing soft drink consumption or follow-up information. Data analyses were performed from February 1, 2018, to October 1, 2018.

Exposure: Consumption of total, sugar-sweetened, and artificially sweetened soft drinks.

Main Outcomes and Measures: Total mortality and cause-specific mortality. Hazard ratios (HRs) and 95% CIs were estimated using multivariable Cox proportional hazards regression models adjusted for other mortality risk factors.

Results: In total, 521 330 individuals were enrolled. Of this total, 451 743 (86.7%) were included in the study, with a mean (SD) age of 50.8 (9.8) years and with 321 081 women (71.1%). During a mean (range) follow-up of 16.4 (11.1 in Greece to 19.2 in France) years, 41 693 deaths occurred. Higher all-cause mortality was found among participants who consumed 2 or more glasses per day (vs consumers of <1 glass per month) of total soft drinks (hazard ratio [HR], 1.17; 95% CI, 1.11-1.22; P < .001), sugar-sweetened soft drinks (HR, 1.08; 95% CI, 1.01-1.16; P = .004), and artificially sweetened soft drinks (HR, 1.26; 95% CI, 1.16-1.35; P < .001). Positive associations were also observed between artificially sweetened soft drinks and deaths from circulatory diseases (≥2 glasses per day vs <1 glass per month; HR, 1.52; 95% CI, 1.30-1.78; P < .001) and between sugar-sweetened soft drinks and deaths from digestive diseases (≥1 glass per day vs <1 glass per month; HR, 1.59; 95% CI, 1.24-2.05; P < .001).

Conclusions and Relevance: This study found that consumption of total, sugar-sweetened, and artificially sweetened soft drinks was positively associated with all-cause deaths in this large European cohort; the results are supportive of public health campaigns aimed at limiting the consumption of soft drinks.

Place, publisher, year, edition, pages
American Medical Association (AMA), 2019
National Category
Dentistry Nutrition and Dietetics
Identifiers
urn:nbn:se:umu:diva-164265 (URN)10.1001/jamainternmed.2019.2478 (DOI)31479109 (PubMedID)2-s2.0-85071732581 (Scopus ID)
Available from: 2019-10-19 Created: 2019-10-19 Last updated: 2019-10-22
Myte, R., Sundkvist, A., van Guelpen, B. & Harlid, S. (2019). Circulating levels of inflammatory markers and DNA methylation, an analysis of repeated samples from a population based cohort. Epigenetics, 14(7), 649-659
Open this publication in new window or tab >>Circulating levels of inflammatory markers and DNA methylation, an analysis of repeated samples from a population based cohort
2019 (English)In: Epigenetics, ISSN 1559-2294, E-ISSN 1559-2308, Vol. 14, no 7, p. 649-659Article in journal (Refereed) Published
Abstract [en]

DNA methylation in blood may adapt to conditions affecting our health, such as inflammation, and multiple studies have identified differential DNA methylation related to smoking, obesity and various diseases. The purpose of this study was to evaluate previously reported, and explore possible new, associations between levels of inflammatory markers and DNA methylation in blood. We used a well-characterized study population consisting of 127 individuals, all of whom were participants in the population-based Vasterbotten Intervention Programme cohort and had provided two blood samples, ten years apart. Levels of CRP and 160 other proteins were measured in plasma, and DNA methylation levels (assessed using the 850K Illumina Infinium MethylationEPIC BeadChip) were measured in white blood cell DNA. Associations between CpG methylation and protein levels were estimated using linear mixed models. In the study we were able to confirm the direction for 85 of 102 previously reported protein-methylation associations. Depicting associations in a network allowed us to identify CpG sites with associations to multiple proteins, and ten CpG sites were each associated with three or more inflammatory markers. Furthermore, two genetic regions included nine additional unreported CpG sites that may represent trans-acting methylation sites. Our study supports a complex interaction between DNA methylation and circulating proteins involved in the inflammatory response. The notion of trans-acting methylation sites affecting, or being affected by, the expression of genes on completely different chromosomes should be taken into account when interpreting results from epigenome-wide association studies.

Place, publisher, year, edition, pages
Taylor & Francis, 2019
Keywords
DNA methylation, inflammation, biomarkers, C, reactive protein, colorectal cancer, risk factors, epigenetics, proteomics
National Category
Medical Genetics Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-160622 (URN)10.1080/15592294.2019.1603962 (DOI)000470485500001 ()31033411 (PubMedID)
Funder
Västerbotten County Council, VLL-547711Västerbotten County Council, VLL-680921Västerbotten County Council
Available from: 2019-06-20 Created: 2019-06-20 Last updated: 2019-06-20Bibliographically approved
Smith, T., Muller, D. C., Moons, K. G. M., Cross, A. J., Johansson, M., Ferrari, P., . . . Tzoulaki, I. (2019). 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, 68, 672-683
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
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2019 (English)In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 68, p. 672-683Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2019
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)000471830300013 ()29615487 (PubMedID)
Funder
NordForskSwedish Cancer SocietySwedish Research CouncilRegion SkåneVästerbotten County Council
Available from: 2018-04-06 Created: 2018-04-06 Last updated: 2019-07-10Bibliographically approved
Aglago, E. K., Huybrechts, I., Murphy, N., Casagrande, C., Nicolas, G., Pischon, T., . . . Gunter, M. J. (2019). Consumption of Fish and Long-chain n-3 Polyunsaturated Fatty Acids Is Associated With Reduced Risk of Colorectal Cancer in a Large European Cohort. Clinical Gastroenterology and Hepatology
Open this publication in new window or tab >>Consumption of Fish and Long-chain n-3 Polyunsaturated Fatty Acids Is Associated With Reduced Risk of Colorectal Cancer in a Large European Cohort
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2019 (English)In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714Article in journal (Refereed) In press
Abstract [en]

BACKGROUND & AIMS: There is an unclear association between intake of fish and long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFAs) and colorectal cancer (CRC). We examined the association between fish consumption, dietary and circulating levels of n-3 LC-PUFAs, and ratio of n-6:n-3 LC-PUFA with CRC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

METHODS: Dietary intake of fish (total, fatty/oily, lean/white) and n-3 LC-PUFA were estimated by food frequency questionnaires given to 521,324 participants in the EPIC study; among these, 6291 individuals developed CRC (median follow up, 14.9 years). Levels of phospholipid LC-PUFA were measured by gas chromatography in plasma samples from a sub-group of 461 CRC cases and 461 matched individuals without CRC (controls). Multivariable Cox proportional hazards and conditional logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs), respectively, with 95% CIs.

RESULTS: Total intake of fish (HR for quintile 5 vs 1, 0.88; 95% CI, 0.80-0.96; Ptrend = .005), fatty fish (HR for quintile 5 vs 1, 0.90; 95% CI, 0.82-0.98; Ptrend = .009), and lean fish (HR for quintile 5 vs 1, 0.91; 95% CI, 0.83-1.00; Ptrend = .016) were inversely associated with CRC incidence. Intake of total n-3 LC-PUFA (HR for quintile 5 vs 1, 0.86; 95% CI, 0.78-0.95; Ptrend = .010) was also associated with reduced risk of CRC, whereas dietary ratio of n-6:n-3 LC-PUFA was associated with increased risk of CRC (HR for quintile 5 vs 1, 1.31; 95% CI, 1.18-1.45; Ptrend < .001). Plasma levels of phospholipid n-3 LC-PUFA was not associated with overall CRC risk, but an inverse trend was observed for proximal compared with distal colon cancer (Pheterogeneity = .026).

CONCLUSIONS: In an analysis of dietary patterns of participants in the EPIC study, we found regular consumption of fish, at recommended levels, to be associated with a lower risk of CRC, possibly through exposure to n-3 LC-PUFA. Levels of n-3 LC-PUFA in plasma were not associated with CRC risk, but there may be differences in risk at different regions of the colon.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Epidemiologic, Omega 3, Seafood, Tumorigenesis
National Category
Nutrition and Dietetics
Identifiers
urn:nbn:se:umu:diva-162704 (URN)10.1016/j.cgh.2019.06.031 (DOI)31252190 (PubMedID)
Available from: 2019-08-26 Created: 2019-08-26 Last updated: 2019-10-10
Nilsson, L. M., Winkvist, A., Esberg, A., Jansson, J.-H., Wennberg, P., van Guelpen, B. & Johansson, I. (2019). Dairy Products and Cancer Risk in a Northern Sweden Population. Nutrition and Cancer
Open this publication in new window or tab >>Dairy Products and Cancer Risk in a Northern Sweden Population
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2019 (English)In: Nutrition and Cancer, ISSN 0163-5581, E-ISSN 1532-7914Article in journal (Refereed) Epub ahead of print
Abstract [en]

The role of dairy products in cancer is unclear. We assessed consumption of fermented milk, non-fermented milk, cheese, and butter, estimated from semi-quantitative food frequency questionnaires, in relation to prospective risk of breast, prostate, colorectal, smoking-, and obesity-related cancers in 101,235 subjects, including 12,552 cancer cases, in the population-based Northern Sweden Health and Disease Study. Most analyses (n = 20) rendered null results. In men, we observed an increased prostate cancer risk among high-consumers of cheese (hazard ratio (HR) for highest vs. lowest quintile (Q5-Q1), 1.11; 95% CI, 0.97-1.27; Ptrend = 0.013). In women, high-consumers of cheese had a decreased risk of overall cancer (HR Q5-Q1, 0.95; 95% CI, 0.88-1.04; Ptrend = 0.039), smoking-related (HR Q5-Q1, 0.84; 95% CI, 0.72-0.97; Ptrend ≤ 0.001), and colorectal cancers (HR Q5-Q1, 0.82; 95% CI, 0.63-1.07; Ptrend = 0.048). Butter yielded a weak decreased obesity-related cancer risk in women (HR Q5-Q1, 0.91; 95% CI, 0.81-1.02; Ptrend = 0.049). Fermented milk yielded HRs below zero in women, but with no clear linear associations. In conclusion, this study does not support any major adverse or beneficial effects of fermented milk, non-fermented milk, cheese, and butter in the diet from a cancer risk perspective.

Place, publisher, year, edition, pages
Taylor & Francis, 2019
Keywords
dairy products, milk, cheese, fermented milk, cancer
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-161682 (URN)10.1080/01635581.2019.1637441 (DOI)000476072800001 ()31298944 (PubMedID)2-s2.0-85068900342 (Scopus ID)
Available from: 2019-07-25 Created: 2019-07-25 Last updated: 2019-08-12
Huyghe, J. R., Bien, S. A., Harrison, T. A., Kang, H. M., Chen, S., Schmit, S. L., . . . Peters, U. (2019). Discovery of common and rare genetic risk variants for colorectal cancer. Nature Genetics, 51(1), 76-+
Open this publication in new window or tab >>Discovery of common and rare genetic risk variants for colorectal cancer
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2019 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 51, no 1, p. 76-+Article in journal (Refereed) Published
Abstract [en]

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 x 10(-8), bringing the number of known independent signals for CRC to similar to 100. New signals implicate lower-frequency variants, Kruppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019
National Category
Medical Genetics Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-155208 (URN)10.1038/s41588-018-0286-6 (DOI)000454108800015 ()30510241 (PubMedID)
Available from: 2019-01-15 Created: 2019-01-15 Last updated: 2019-01-15Bibliographically approved
Bien, S. A., Su, Y.-R., Conti, D. V., Harrison, T. A., Qu, C., Guo, X., . . . Peters, U. (2019). Genetic variant predictors of gene expression provide new insight into risk of colorectal cancer. Human Genetics, 138(4), 307-326
Open this publication in new window or tab >>Genetic variant predictors of gene expression provide new insight into risk of colorectal cancer
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2019 (English)In: Human Genetics, ISSN 0340-6717, E-ISSN 1432-1203, Vol. 138, no 4, p. 307-326Article in journal (Refereed) Published
Abstract [en]

Genome-wide association studies have reported 56 independently associated colorectal cancer (CRC) risk variants, most of which are non-coding and believed to exert their effects by modulating gene expression. The computational method PrediXcan uses cis-regulatory variant predictors to impute expression and perform gene-level association tests in GWAS without directly measured transcriptomes. In this study, we used reference datasets from colon (n=169) and whole blood (n=922) transcriptomes to test CRC association with genetically determined expression levels in a genome-wide analysis of 12,186 cases and 14,718 controls. Three novel associations were discovered from colon transverse models at FDR0.2 and further evaluated in an independent replication including 32,825 cases and 39,933 controls. After adjusting for multiple comparisons, we found statistically significant associations using colon transcriptome models with TRIM4 (discovery P=2.2x10(-4), replication P=0.01), and PYGL (discovery P=2.3x10(-4), replication P=6.7x10(-4)). Interestingly, both genes encode proteins that influence redox homeostasis and are related to cellular metabolic reprogramming in tumors, implicating a novel CRC pathway linked to cell growth and proliferation. Defining CRC risk regions as one megabase up- and downstream of one of the 56 independent risk variants, we defined 44 non-overlapping CRC-risk regions. Among these risk regions, we identified genes associated with CRC (P<0.05) in 34/44 CRC-risk regions. Importantly, CRC association was found for two genes in the previously reported 2q25 locus, CXCR1 and CXCR2, which are potential cancer therapeutic targets. These findings provide strong candidate genes to prioritize for subsequent laboratory follow-up of GWAS loci. This study is the first to implement PrediXcan in a large colorectal cancer study and findings highlight the utility of integrating transcriptome data in GWAS for discovery of, and biological insight into, risk loci.

Place, publisher, year, edition, pages
Springer, 2019
National Category
Medical Genetics
Identifiers
urn:nbn:se:umu:diva-159075 (URN)10.1007/s00439-019-01989-8 (DOI)000465974800002 ()30820706 (PubMedID)
Note

Correction: Bien, S.A., Su, YR., Conti, D.V. et al. Hum Gen. (2019) 138: 789. DOI: 10.1007/s00439-019-02030-8

Available from: 2019-05-20 Created: 2019-05-20 Last updated: 2019-08-07Bibliographically approved
Myte, R., Gylling, B., Häggström, J., Häggström, C., Zingmark, C., Löfgren Burström, A., . . . van Guelpen, B. (2019). Metabolic factors and the risk of colorectal cancer by KRAS and BRAF mutation status. International Journal of Cancer, 145(2), 327-337
Open this publication in new window or tab >>Metabolic factors and the risk of colorectal cancer by KRAS and BRAF mutation status
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2019 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 145, no 2, p. 327-337Article in journal (Refereed) Published
Abstract [en]

Factors related to energy metabolism and the metabolic syndrome, such as higher body mass index (BMI), blood glucose, or blood lipids, and blood pressure, are associated with an increased risk of colorectal cancer (CRC). However, CRC is a heterogeneous disease, developing through distinct pathways with differences in molecular characteristics and prognosis, and possibly also in risk factors. For subtypes defined by KRAS and BRAF mutation status, BMI is the only metabolic factor previously studied, with inconsistent findings. We investigated whether associations between BMI, blood glucose, blood lipids, and blood pressure and CRC risk differed by tumor KRAS and BRAF mutation status in 117,687 participants from two population-based cohorts within the Northern Sweden Health and Disease Study (NSHDS). Hazard ratios (HRs) for overall CRC and CRC subtypes by metabolic factors were estimated with Cox proportional hazards regression, using multiple imputation to handle missing exposure and tumor data. During a median follow-up of 15.6 years, we acquired 1,250 prospective CRC cases, of which 766 cases had complete baseline and molecular tumor data. Consistent with previous evidence, higher BMI, total cholesterol, triglyceride levels, and blood pressure were associated with an increased risk of overall CRC (HRs per 1 standard deviation increase: 1.07 to 1.12). These associations were similar regardless of CRC subtype by KRAS and BRAF mutation status (all pheterogeneity > 0.05). The same was true for subtypes based on microsatellite instability status. Poor metabolic health may therefore be a universal mechanism for colorectal cancer, acting across multiple developmental pathways.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019
Keywords
BRAF, KRAS, colorectal cancer, metabolic factors, microsatellite instability, risk factors
National Category
Cancer and Oncology Nutrition and Dietetics
Identifiers
urn:nbn:se:umu:diva-158782 (URN)10.1002/ijc.32104 (DOI)30613980 (PubMedID)2-s2.0-85060622510 (Scopus ID)
Note

Originally included in thesis in manuscript form with title [Metabolic factors and colorectal cancer risk by KRAS and BRAF mutation status]

Available from: 2019-05-08 Created: 2019-05-08 Last updated: 2019-06-11Bibliographically approved
Schmit, S. L., Edlund, C. K., Schumacher, F. R., Gong, J., Harrison, T. A., Huyghe, J. R., . . . Gruber, S. B. (2019). Novel Common Genetic Susceptibility Loci for Colorectal Cancer. Journal of the National Cancer Institute, 111(2), 146-157
Open this publication in new window or tab >>Novel Common Genetic Susceptibility Loci for Colorectal Cancer
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2019 (English)In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 111, no 2, p. 146-157Article in journal (Refereed) Published
Abstract [en]

Background: Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5x10(-8)) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk.

Methods: We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5x10(-8)) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided.

Results: The discovery GWAS identified 11 variants associated with CRC at P < 5x10(-8), of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0.

Conclusions: This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.

Place, publisher, year, edition, pages
Oxford University Press, 2019
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-159635 (URN)10.1093/jnci/djy099 (DOI)000467900500008 ()29917119 (PubMedID)
Available from: 2019-06-05 Created: 2019-06-05 Last updated: 2019-06-05Bibliographically approved
Gylling, B., Myte, R., Ulvik, A., Ueland, P. M., Midttun, Ø., Schneede, J., . . . Palmqvist, R. (2019). One-carbon metabolite ratios as functional B-vitamin markers and in relation to colorectal cancer risk. International Journal of Cancer, 144(5), 947-956
Open this publication in new window or tab >>One-carbon metabolite ratios as functional B-vitamin markers and in relation to colorectal cancer risk
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2019 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 144, no 5, p. 68p. 947-956Article in journal (Other academic) Published
Abstract [en]

Background: One-carbon metabolism biomarker are easily measured in plasma, but analyzing them one at a time in relation to disease does not take into account the interdependence of the many factors involved. The relative dynamics of major one-carbon metabolism branches can be assessed by relating the functional B-vitamin marker total homocysteine (tHcy) to transsulfuration (total cysteine) and methylation (creatinine) outputs.

Objective: We validated the ratios of tHcy to total cysteine (Hcy:Cys), tHcy to creatinine (Hcy:Cre), and tHcy to cysteine to creatinine (Hcy:Cys:Cre) as functional markers of B-vitamin status. We also calculated the associations of these ratios to colorectal cancer (CRC) risk.

Design: The relative contribution of potential confounders to the variance of the ratio-based B-vitamin markers was calculated by linear regression in a nested case-control study of 613 CRC cases and 1211 matched controls. Total B-vitamin status was represented by a summary score comprising Z-standardized plasma concentrations of folate, cobalamin, betaine, pyridoxal 5´-phosphate, and riboflavin. Associations with CRC risk were estimated using conditional logistic regression.

Results: The ratio-based B-vitamin markers all outperformed tHcy as markers of total B-vitamin status, in both CRC cases and controls. Associations with CRC risk were similar for the ratio-based B-vitamin markers and total B-vitamin status (approximately 25% lower risk for high versus low B-vitamin status).

Conclusions: Ratio-based B-vitamin markers were good predictors of total B-vitamin status, and displayed similar associations with CRC risk. Since tHcy and creatinine are routinely clinically analyzed, Hcy:Cre could be easily implemented in clinical practice to aid interpretation of tHcy results.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019. p. 68
Keywords
Biomarkers, colorectal cancer, metabolite ratios, B-vitamins, one-carbon metabolism
National Category
Clinical Laboratory Medicine
Research subject
Cancer Epidemiology
Identifiers
urn:nbn:se:umu:diva-142854 (URN)10.1002/ijc.31606 (DOI)000455041700003 ()29786139 (PubMedID)
Funder
Swedish Cancer Society, 12/501Swedish Cancer Society, 14/780
Note

Originally included in thesis in manuscript form

Available from: 2017-12-12 Created: 2017-12-12 Last updated: 2019-02-14Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-9692-101x

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