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Johansson, Ingegerd
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Publications (10 of 257) Show all publications
Murphy, N., Achaintre, D., Zamora-Ros, R., Jenab, M., Boutron-Ruault, M.-C., Carbonnel, F., . . . Scalbert, A. (2018). A prospective evaluation of plasma polyphenol levels and colon cancer risk. International Journal of Cancer, 143(7), 1620-1631
Open this publication in new window or tab >>A prospective evaluation of plasma polyphenol levels and colon cancer risk
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2018 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 143, no 7, p. 1620-1631Article in journal (Refereed) Published
Abstract [en]

Polyphenols have been shown to exert biological activity in experimental models of colon cancer; however, human data linking specific polyphenols to colon cancer is limited. We assessed the relationship between pre-diagnostic plasma polyphenols and colon cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition study. Using high pressure liquid chromatography coupled to tandem mass spectrometry, we measured concentrations of 35 polyphenols in plasma from 809 incident colon cancer cases and 809 matched controls. We used multivariable adjusted conditional logistic regression models that included established colon cancer risk factors. The false discovery rate (qvalues ) was computed to control for multiple comparisons. All statistical tests were two-sided. After false discovery rate correction and in continuous log2 -transformed multivariable models, equol (odds ratio [OR] per log2 -value, 0.86, 95% confidence interval [95% CI] = 0.79-0.93; qvalue  = 0.01) and homovanillic acid (OR per log2 -value, 1.46, 95% CI = 1.16-1.84; qvalue  = 0.02) were associated with colon cancer risk. Comparing extreme fifths, equol concentrations were inversely associated with colon cancer risk (OR = 0.61, 95% CI = 0.41-0.91, ptrend  = 0.003), while homovanillic acid concentrations were positively associated with colon cancer development (OR = 1.72, 95% CI = 1.17-2.53, ptrend  < 0.0001). No heterogeneity for these associations was observed by sex and across other colon cancer risk factors. The remaining polyphenols were not associated with colon cancer risk. Higher equol concentrations were associated with lower risk, and higher homovanillic acid concentrations were associated with greater risk of colon cancer. These findings support a potential role for specific polyphenols in colon tumorigenesis.

Place, publisher, year, edition, pages
John Wiley & Sons, 2018
Keywords
EPIC, biomarkers, colon cancer, nested case-control study, polyphenols
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-151155 (URN)10.1002/ijc.31563 (DOI)000443392100008 ()29696648 (PubMedID)
Available from: 2018-08-29 Created: 2018-08-29 Last updated: 2018-10-25Bibliographically approved
Kindstedt, E., Johansson, L., Palmqvist, P., Koskinen Holm, C., Kokkonen, H., Johansson, I., . . . Lundberg, P. (2018). Association between marginal jawbone loss and the onset of rheumatoid arhtritis and relationship to plasma levels of RANKL. Arthritis & Rheumatology, 70(4), 508-515
Open this publication in new window or tab >>Association between marginal jawbone loss and the onset of rheumatoid arhtritis and relationship to plasma levels of RANKL
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2018 (English)In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 70, no 4, p. 508-515Article in journal (Refereed) Published
Abstract [en]

Objective: To investigate whether periodontitis, characterized by marginal jawbone loss, precedes the onset of symptoms of rheumatoid arthritis (RA), and to analyze plasma levels of RANKL (a cytokine that is crucial for bone resorption) and anti–citrullinated peptide antibodies (ACPAs) in presymptomatic individuals compared with matched referent controls.

Methods: Marginal jawbone loss was measured on dental radiographs of the premolar/molar regions in the jaws in 176 subjects, 93 of whom subsequently developed RA. Among these participating subjects, 46 had documented radiographs predating symptom onset, and 45 cases could be matched to controls, according to sex, age, and smoking status. Plasma RANKL concentrations were analyzed using enzyme‐linked immunosorbent assay. A receiver operating characteristic curve was used to define the cutoff value for RANKL positivity.

Results: Bone loss was significantly greater in presymptomatic subjects classified as never smokers compared with that in controls, and increasing levels of bone loss were associated with a higher risk of the subsequent development of RA (hazard ratio 1.03, 95% confidence interval 1.01–1.05). No association between jawbone loss and RA was observed in smokers. A significantly greater extent of marginal jawbone loss was detected in RANKL‐positive presymptomatic subjects, and even more pronounced jawbone loss was observed in those who were positive for both RANKL and ACPA.

Conclusion: Marginal jawbone loss preceded the clinical onset of RA symptoms, but this was observed only in nonsmokers. Moreover, marginal jawbone loss was significantly greater in RANKL‐positive presymptomatic subjects compared with RANKL‐negative presymptomatic subjects and was highest in presymptomatic subjects positive for both ACPA and RANKL.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2018
National Category
Rheumatology and Autoimmunity
Research subject
Medicine, rheumatology; Odontology
Identifiers
urn:nbn:se:umu:diva-146131 (URN)10.1002/art.40394 (DOI)000428697300005 ()29195021 (PubMedID)
Available from: 2018-04-03 Created: 2018-04-03 Last updated: 2018-08-07Bibliographically approved
Haworth, S., Shungin, D., van der Tas, J. T., Vucic, S., Medina-Gomez, C., Yakimov, V., . . . Timpson, N. J. (2018). Consortium-based genome-wide meta-analysis for childhood dental caries traits. Human Molecular Genetics, 27(17), 3113-3127
Open this publication in new window or tab >>Consortium-based genome-wide meta-analysis for childhood dental caries traits
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2018 (English)In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 27, no 17, p. 3113-3127Article in journal (Refereed) Published
Abstract [en]

Prior studies suggest dental caries traits in children and adolescents are partially heritable, but there has been no large-scale consortium genome-wide association study (GWAS) to date. We therefore performed GWAS for caries in participants aged 2.5-18.0 years from nine contributing centres. Phenotype definitions were created for the presence or absence of treated or untreated caries, stratified by primary and permanent dentition. All studies tested for association between caries and genotype dosage and the results were combined using fixed-effects meta-analysis. Analysis included up to 19 003 individuals (7530 affected) for primary teeth and 13 353 individuals (5875 affected) for permanent teeth. Evidence for association with caries status was observed at rs1594318-C for primary teeth [intronic within ALLC, odds ratio (OR) 0.85, effect allele frequency (EAF) 0.60, P 4.13e-8] and rs7738851-A (intronic within NEDD9, OR 1.28, EAF 0.85, P 1.63e-8) for permanent teeth. Consortium-wide estimated heritability of caries was low [h2 of 1% (95% CI: 0%: 7%) and 6% (95% CI 0%: 13%) for primary and permanent dentitions, respectively] compared with corresponding within-study estimates [h2 of 28% (95% CI: 9%: 48%) and 17% (95% CI: 2%: 31%)] or previously published estimates. This study was designed to identify common genetic variants with modest effects which are consistent across different populations. We found few single variants associated with caries status under these assumptions. Phenotypic heterogeneity between cohorts and limited statistical power will have contributed; these findings could also reflect complexity not captured by our study design, such as genetic effects which are conditional on environmental exposure.

Place, publisher, year, edition, pages
Oxford University Press, 2018
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-151020 (URN)10.1093/hmg/ddy237 (DOI)000444202300012 ()29931343 (PubMedID)
Available from: 2018-08-23 Created: 2018-08-23 Last updated: 2018-10-02Bibliographically approved
Huang, T., Ding, M., Bergholdt, H. K. M., Wang, T., Heianza, Y., Sun, D.-j., . . . Qi, L. (2018). Dairy Consumption and Body Mass Index Among Adults: Mendelian Randomization Analysis of 184802 Individuals from 25 Studies. Clinical Chemistry, 64(1), 183-191
Open this publication in new window or tab >>Dairy Consumption and Body Mass Index Among Adults: Mendelian Randomization Analysis of 184802 Individuals from 25 Studies
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2018 (English)In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 64, no 1, p. 183-191Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Associations between dairy intake and body mass index (BMI) have been inconsistently observed in epidemiological studies, and the causal relationship remains ill defined.

METHODS: We performed Mendelian randomization (MR) analysis using an established dairy intake-associated genetic polymorphism located upstream of the lactase gene (LCT-13910 C/T, rs4988235) as an instrumental variable (IV). Linear regression models were fitted to analyze associations between (a) dairy intake and BMI, (b) rs4988235 and dairy intake, and (c) rs4988235 and BMI in each study. The causal effect of dairy intake on BMI was quantified by IV estimators among 184802 participants from 25 studies.

RESULTS: Higher dairy intake was associated with higher BMI (β = 0.03 kg/m2 per serving/day; 95% CI, 0.00–0.06; P = 0.04), whereas the LCT genotype with 1 or 2 T allele was significantly associated with 0.20 (95% CI, 0.14–0.25) serving/day higher dairy intake (P = 3.15 × 10−12) and 0.12 (95% CI, 0.06–0.17) kg/m2 higher BMI (P = 2.11 × 10−5). MR analysis showed that the genetically determined higher dairy intake was significantly associated with higher BMI (β = 0.60 kg/m2 per serving/day; 95% CI, 0.27–0.92; P = 3.0 × 10−4).

CONCLUSIONS: The present study provides strong evidence to support a causal effect of higher dairy intake on increased BMI among adults.

National Category
Nutrition and Dietetics
Identifiers
urn:nbn:se:umu:diva-144092 (URN)10.1373/clinchem.2017.280701 (DOI)000419121500026 ()29187356 (PubMedID)
Available from: 2018-01-26 Created: 2018-01-26 Last updated: 2018-06-09Bibliographically approved
Johansson, I., Nilsson, L. M., Esberg, A., Jansson, J.-H. & Winkvist, A. (2018). Dairy intake revisited - associations between dairy intake and lifestyle related cardio-metabolic risk factors in a high milk consuming population. Nutrition Journal, 17, Article ID 110.
Open this publication in new window or tab >>Dairy intake revisited - associations between dairy intake and lifestyle related cardio-metabolic risk factors in a high milk consuming population
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2018 (English)In: Nutrition Journal, ISSN 1475-2891, E-ISSN 1475-2891, Vol. 17, article id 110Article in journal (Refereed) Published
Abstract [en]

Background: The association between milk and dairy intake and the incidence of cardiometabolic diseases, cancer and mortality has been evaluated in many studies, but these studies have had conflicting results with no clear conclusion on causal or confounding associations. The present study aims to further address this association by cross-sectional and longitudinal evaluation of the associations between exposure to various types of dairy products and metabolic risk markers among inhabitants in northern Sweden while taking other lifestyle factors into account.

Methods: Respondents in the Vasterbotten Intervention Programme with complete and plausible diet data between 1991 and 2016 were included, yielding 124,934 observations from 90,512 unique subjects. For longitudinal analysis, 27,682 participants with a visit 8-12years after the first visit were identified. All participants completed a validated Food Frequency Questionnaire. Metabolic risk markers, including body mass index (BMI), blood pressure, serum (S) cholesterol and triglycerides, and blood glucose, were measured. Participants were categorized into quintiles by intake of dairy products, and risk (odds ratios, OR) of undesirable levels of metabolic risk markers was assessed in multivariable logistic regression analyses. In longitudinal analyses, intake quintiles were related to desirable levels of metabolic risk markers at both visits or deterioration at follow-up using Cox regression analyses.

Results: The OR of being classified with an undesirable BMI decreased with increasing quintiles of total dairy, cheese and butter intake but increased with increasing non-fermented milk intake. The OR of being classified with an undesirable S-cholesterol level increased with increasing intake of total dairy, butter and high fat (3%) non-fermented milk, whereas an undesirable S-triglyceride level was inversely associated with cheese and butter intake in women. In longitudinal analyses, increasing butter intake was associated with deterioration of S-cholesterol and blood glucose levels, whereas increasing cheese intake was associated with a lower risk of deterioration of S-triglycerides.

Conclusions: Confounding factors likely contribute to the demonstrated association between dairy intake and mortality, and other medical conditions and analyses should be stratified by dairy type.

Place, publisher, year, edition, pages
BioMed Central, 2018
Keywords
Dairy products, Milk, Cheese, Butter, Fermented milk, Non-fermented milk, BMI, Serum lipids, Blood glucose, Blood pressure
National Category
Nutrition and Dietetics Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-154046 (URN)10.1186/s12937-018-0418-y (DOI)000451026300003 ()30466440 (PubMedID)
Funder
Forte, Swedish Research Council for Health, Working Life and WelfareSwedish Research Council
Available from: 2018-12-19 Created: 2018-12-19 Last updated: 2018-12-19Bibliographically approved
Naudin, S., Li, K., Jaouen, T., Assi, N., Kyrø, C., Tjønneland, A., . . . Ferrari, P. (2018). Lifetime and baseline alcohol intakes and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition study. International Journal of Cancer, 143(4), 801-812
Open this publication in new window or tab >>Lifetime and baseline alcohol intakes and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition study
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2018 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 143, no 4, p. 801-812Article in journal (Refereed) Published
Abstract [en]

Recent evidence suggested a weak relationship between alcohol consumption and pancreatic cancer (PC) risk. In our study, the association between lifetime and baseline alcohol intakes and the risk of PC was evaluated, including the type of alcoholic beverages and potential interaction with smoking. Within the European Prospective Investigation into Cancer and Nutrition (EPIC) study, 1,283 incident PC (57% women) were diagnosed from 476,106 cancer-free participants, followed up for 14 years. Amounts of lifetime and baseline alcohol were estimated through lifestyle and dietary questionnaires, respectively. Cox proportional hazard models with age as primary time variable were used to estimate PC hazard ratios (HR) and their 95% confidence interval (CI). Alcohol intake was positively associated with PC risk in men. Associations were mainly driven by extreme alcohol levels, with HRs comparing heavy drinkers (>60 g/day) to the reference category (0.1-4.9 g/day) equal to 1.77 (95% CI: 1.06, 2.95) and 1.63 (95% CI: 1.16, 2.29) for lifetime and baseline alcohol, respectively. Baseline alcohol intakes from beer (>40 g/day) and spirits/liquors (>10 g/day) showed HRs equal to 1.58 (95% CI: 1.07, 2.34) and 1.41 (95% CI: 1.03, 1.94), respectively, compared to the reference category (0.1-2.9 g/day). In women, HR estimates did not reach statistically significance. The alcohol and PC risk association was not modified by smoking status. Findings from a large prospective study suggest that baseline and lifetime alcohol intakes were positively associated with PC risk, with more apparent risk estimates for beer and spirits/liquors than wine intake.

National Category
Clinical Medicine
Identifiers
urn:nbn:se:umu:diva-146524 (URN)10.1002/ijc.31367 (DOI)000438203500009 ()29524225 (PubMedID)
Available from: 2018-04-11 Created: 2018-04-11 Last updated: 2018-09-19Bibliographically approved
Eriksson, L., Lif Holgerson, P., Esberg, A. & Johansson, I. (2018). Microbial complexes and caries in 17-year-olds with and without Streptococcus mutans. Journal of Dental Research, 97(3), 275-282
Open this publication in new window or tab >>Microbial complexes and caries in 17-year-olds with and without Streptococcus mutans
2018 (English)In: Journal of Dental Research, ISSN 0022-0345, E-ISSN 1544-0591, Vol. 97, no 3, p. 275-282Article in journal (Refereed) Published
Abstract [en]

Streptococcus mutans is a key bacterial species in the caries process, which affects >90% of the population worldwide. However, other acidogenic and aciduric/acidophilic species may contribute to disease development. In Sweden, a country with low prevalences of caries and S. mutans, a significant portion of caries-affected adolescents lack detectable levels of S. mutans. The objectives of the present study were 1) to characterize the tooth biofilm and saliva microbiota of adolescents with caries disease, with or without detectable S. mutans, from tooth biofilm and saliva samples and 2) to assess taxa clustering in the tooth biofilm and saliva samples and relate this information to caries status. For 17-y-old participants ( N = 154), enamel and dentin caries (the total number of present carious surfaces in the enamel and dentin) and caries experience (the number of decayed and filled tooth surfaces) were recorded, dental biofilm and saliva samples obtained, and information on medical and lifestyle habits collected. Multiplex 16S rDNA (V3-V4) sequencing of bacterial DNA was performed with the Illumina MiSeq platform. The Human Oral Microbiome Database and the ProbeSeq pipeline were used in the HOMI NGS procedure. In subjects with caries experience, high levels of S. mutans were associated with a few species and low levels with a panel of saccharolytic species. Present caries was similarly associated with a panel of saccharolytic species in subjects without S. mutans. Furthermore, tooth biofilm microbiota could be used to establish 4 clusters of subjects with different caries experiences. In particular, high levels of S. mutans were associated with the presence of a few influential species in multivariate modeling, including Scardovia wiggsiae. By contrast, a panel of less avid lactic acid-producing species was influential in patients with undetectable or low S. mutans levels in such modeling. These findings support a prominent role of S. mutans in infected adolescents but also the ecologic concept, especially in S. mutans-free subjects.

Place, publisher, year, edition, pages
Thousand oaks: Sage Publications, 2018
Keywords
microbiota, saliva, tooth biofilm, adolescents, 16S, high-throughput nucleotide sequencing
National Category
Dentistry
Identifiers
urn:nbn:se:umu:diva-139760 (URN)10.1177/0022034517731758 (DOI)000429319800005 ()28930642 (PubMedID)
Available from: 2017-09-21 Created: 2017-09-21 Last updated: 2018-06-09Bibliographically approved
Deschasaux, M., Huybrechts, I., Murphy, N., Julia, C., Hercberg, S., Srour, B., . . . Touvier, M. (2018). Nutritional quality of food as represented by the FSAm-NPS nutrient profiling system underlying the Nutri-Score label and cancer risk in Europe: results from the EPIC prospective cohort study. PLoS Medicine, 15(9), Article ID e1002651.
Open this publication in new window or tab >>Nutritional quality of food as represented by the FSAm-NPS nutrient profiling system underlying the Nutri-Score label and cancer risk in Europe: results from the EPIC prospective cohort study
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2018 (English)In: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 15, no 9, article id e1002651Article in journal (Refereed) Published
Abstract [en]

Background

Helping consumers make healthier food choices is a key issue for the prevention of cancer and other diseases. In many countries, political authorities are considering the implementation of a simplified labelling system to reflect the nutritional quality of food products. The Nutri-Score, a five-colour nutrition label, is derived from the Nutrient Profiling System of the British Food Standards Agency (modified version) (FSAm-NPS). How the consumption of foods with high/low FSAm-NPS relates to cancer risk has been studied in national/regional cohorts but has not been characterized in diverse European populations.

Methods and findings

This prospective analysis included 471,495 adults from the European Prospective Investigation into Cancer and Nutrition (EPIC, 1992-2014, median follow-up: 15.3 y), among whom there were 49,794 incident cancer cases (main locations: breast, n = 12,063; prostate, n = 6,745; colon-rectum, n = 5,806). Usual food intakes were assessed with standardized country-specific diet assessment methods. The FSAm-NPS was calculated for each food/beverage using their 100-g content in energy, sugar, saturated fatty acid, sodium, fibres, proteins, and fruits/vegetables/legumes/nuts. The FSAm-NPS scores of all food items usually consumed by a participant were averaged to obtain the individual FSAm-NPS Dietary Index (DI) scores. Multi-adjusted Cox proportional hazards models were computed. A higher FSAm-NPS DI score, reflecting a lower nutritional quality of the food consumed, was associated with a higher risk of total cancer (HRQ5 versus (Q1) = 1.07; 95% CI 1.03-1.10, P-trend < 0.001). Absolute cancer rates in those with high and low (quintiles 5 and 1) FSAm-NPS DI scores were 81.4 and 69.5 cases/10,000 person-years, respectively. Higher FSAm-NPS DI scores were specifically associated with higher risks of cancers of the colon-rectum, upper aerodigestive tract and stomach, lung for men, and liver and postmenopausal breast for women (all P < 0.05). The main study limitation is that it was based on an observational cohort using self-reported dietary data obtained through a single baseline food frequency questionnaire; thus, exposure misclassification and residual confounding cannot be ruled out.

Conclusions

In this large multinational European cohort, the consumption of food products with a higher FSAm-NPS score (lower nutritional quality) was associated with a higher risk of cancer. This supports the relevance of the FSAm-NPS as underlying nutrient profiling system for front-of-pack nutrition labels, as well as for other public health nutritional measures.

Place, publisher, year, edition, pages
Public Library Science, 2018
National Category
Nutrition and Dietetics
Identifiers
urn:nbn:se:umu:diva-153825 (URN)10.1371/journal.pmed.1002651 (DOI)000445914900004 ()30226842 (PubMedID)
Funder
Swedish Cancer SocietySwedish Research CouncilRegion SkåneVästerbotten County Council
Available from: 2018-12-11 Created: 2018-12-11 Last updated: 2018-12-11Bibliographically approved
Myte, R., Gylling, B., Häggström, J., Schneede, J., Löfgren-Burström, A., Huyghe, J. R., . . . Van Guelpen, B. (2018). One-carbon metabolism biomarkers and genetic variants in relation to colorectal cancer risk by KRAS and BRAF mutation status. PLoS ONE, 13(4), Article ID e0196233.
Open this publication in new window or tab >>One-carbon metabolism biomarkers and genetic variants in relation to colorectal cancer risk by KRAS and BRAF mutation status
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2018 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 4, article id e0196233Article in journal (Refereed) Published
Abstract [en]

Disturbances in one-carbon metabolism, intracellular reactions involved in nucleotide synthesis and methylation, likely increase the risk of colorectal cancer (CRC). However, results have been inconsistent. To explore whether this inconsistency could be explained by intertumoral heterogeneity, we evaluated a comprehensive panel of one-carbon metabolism biomarkers and some single nucleotide polymorphisms (SNPs) in relation to the risk of molecular subtypes of CRC defined by mutations in the KRAS and BRAF oncogenes. This nested case-control study included 488 CRC cases and 947 matched controls from two population-based cohorts in the Northern Sweden Health and Disease Study. We analyzed 14 biomarkers and 17 SNPs in prediagnostic blood and determined KRAS and BRAF mutation status in tumor tissue. In a multivariate network analysis, no variable displayed a strong association with the risk of specific CRC subtypes. A non-synonymous SNP in the CTH gene, rs1021737, had a stronger association compared with other variables. In subsequent univariate analyses, participants with variant rs1021737 genotype had a decreased risk of KRAS-mutated CRC (OR per allele = 0.72, 95% CI = 0.50, 1.05), and an increased risk of BRAF-mutated CRC (OR per allele = 1.56, 95% CI = 1.07, 2.30), with weak evidence for heterogeneity (Pheterogeneity = 0.01). This subtype-specific SNP association was not replicated in a case-case analysis of 533 CRC cases from The Cancer Genome Atlas (P = 0.85). In conclusion, we found no support for clear subtype-specific roles of one-carbon metabolism biomarkers and SNPs in CRC development, making differences in CRC molecular subtype distributions an unlikely explanation for the varying results on the role of one-carbon metabolism in CRC development across previous studies. Further investigation of the CTH gene in colorectal carcinogenesis with regards to KRAS and BRAF mutations or other molecular characteristics of the tumor may be warranted.

Place, publisher, year, edition, pages
Public Library of Science, 2018
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-147822 (URN)10.1371/journal.pone.0196233 (DOI)000430802400077 ()29694444 (PubMedID)
Available from: 2018-05-21 Created: 2018-05-21 Last updated: 2018-09-12Bibliographically approved
Gylling, B., Myte, R., Ulvik, A., Ueland, P. M., Midttun, Ø., Schneede, J., . . . Palmqvist, R. (2018). One-carbon metabolite ratios as functional B-vitamin markers and in relation to colorectal cancer risk. International Journal of Cancer
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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2018 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, , p. 68Article in journal (Other academic) Epub ahead of print
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, 2018. 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)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: 2019-01-18
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