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van Guelpen, BethanyORCID iD iconorcid.org/0000-0002-9692-101X
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Publications (10 of 160) Show all publications
Rontogianni, M. O., Bouras, E., Aglago, E. K., Freisling, H., Murphy, N., Cotterchio, M., . . . Tsilidis, K. K. (2024). Allometric versus traditional body-shape indices and risk of colorectal cancer: a Mendelian randomization analysis. International Journal of Obesity
Open this publication in new window or tab >>Allometric versus traditional body-shape indices and risk of colorectal cancer: a Mendelian randomization analysis
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2024 (English)In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497Article in journal (Refereed) Epub ahead of print
Abstract [en]

Background: Traditional body-shape indices such as Waist Circumference (WC), Hip Circumference (HC), and Waist-to-Hip Ratio (WHR) are associated with colorectal cancer (CRC) risk, but are correlated with Body Mass Index (BMI), and adjustment for BMI introduces a strong correlation with height. Thus, new allometric indices have been developed, namely A Body Shape Index (ABSI), Hip Index (HI), and Waist-to-Hip Index (WHI), which are uncorrelated with weight and height; these have also been associated with CRC risk in observational studies, but information from Mendelian randomization (MR) studies is missing.

Methods: We used two-sample MR to examine potential causal cancer site- and sex-specific associations of the genetically-predicted allometric body-shape indices with CRC risk, and compared them with BMI-adjusted traditional body-shape indices, and BMI. Data were obtained from UK Biobank and the GIANT consortium, and from GECCO, CORECT and CCFR consortia.

Results: WHI was positively associated with CRC in men (OR per SD: 1.20, 95% CI: 1.03–1.39) and in women (1.15, 1.06–1.24), and similarly for colon and rectal cancer. ABSI was positively associated with colon and rectal cancer in men (1.27, 1.03–1.57; and 1.40, 1.10–1.77, respectively), and with colon cancer in women (1.20, 1.07–1.35). There was little evidence for association between HI and colon or rectal cancer. The BMI-adjusted WHR and HC showed similar associations to WHI and HI, whereas WC showed similar associations to ABSI only in women.

Conclusions: This large MR study provides strong evidence for a potential causal positive association of the allometric indices ABSI and WHI with CRC in both sexes, thus establishing the association between abdominal fat and CRC without the limitations of the traditional waist size indices and independently of BMI. Among the BMI-adjusted traditional indices, WHR and HC provided equivalent associations with WHI and HI, while differences were observed between WC and ABSI.

Place, publisher, year, edition, pages
Springer Nature, 2024
National Category
Cancer and Oncology Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-220884 (URN)10.1038/s41366-024-01479-6 (DOI)001155394800003 ()38297030 (PubMedID)2-s2.0-85183703929 (Scopus ID)
Funder
NIH (National Institutes of Health)
Available from: 2024-02-14 Created: 2024-02-14 Last updated: 2024-02-14
Harewood, R., Rothwell, J. A., Bešević, J., Viallon, V., Achaintre, D., Gicquiau, A., . . . Gunter, M. J. (2024). Association between pre-diagnostic circulating lipid metabolites and colorectal cancer risk: a nested case–control study in the European Prospective Investigation into Cancer and Nutrition (EPIC). EBioMedicine, 101, Article ID 105024.
Open this publication in new window or tab >>Association between pre-diagnostic circulating lipid metabolites and colorectal cancer risk: a nested case–control study in the European Prospective Investigation into Cancer and Nutrition (EPIC)
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2024 (English)In: EBioMedicine, E-ISSN 2352-3964, Vol. 101, article id 105024Article in journal (Refereed) Published
Abstract [en]

Background: Altered lipid metabolism is a hallmark of cancer development. However, the role of specific lipid metabolites in colorectal cancer development is uncertain.

Methods: In a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined associations between pre-diagnostic circulating concentrations of 97 lipid metabolites (acylcarnitines, glycerophospholipids and sphingolipids) and colorectal cancer risk. Circulating lipids were measured using targeted mass spectrometry in 1591 incident colorectal cancer cases (55% women) and 1591 matched controls. Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between concentrations of individual lipid metabolites and metabolite patterns with colorectal cancer risk.

Findings: Of the 97 assayed lipids, 24 were inversely associated (nominally p < 0.05) with colorectal cancer risk. Hydroxysphingomyelin (SM (OH)) C22:2 (ORper doubling 0.60, 95% CI 0.47–0.77) and acylakyl-phosphatidylcholine (PC ae) C34:3 (ORper doubling 0.71, 95% CI 0.59–0.87) remained associated after multiple comparisons correction. These associations were unaltered after excluding the first 5 years of follow-up after blood collection and were consistent according to sex, age at diagnosis, BMI, and colorectal subsite. Two lipid patterns, one including 26 phosphatidylcholines and all sphingolipids, and another 30 phosphatidylcholines, were weakly inversely associated with colorectal cancer.

Interpretation: Elevated pre-diagnostic circulating levels of SM (OH) C22:2 and PC ae C34:3 and lipid patterns including phosphatidylcholines and sphingolipids were associated with lower colorectal cancer risk. This study may provide insight into potential links between specific lipids and colorectal cancer development. Additional prospective studies are needed to validate the observed associations. Funding: World Cancer Research Fund (reference: 2013/1002); European Commission (FP7: BBMRI-LPC; reference: 313010).

Place, publisher, year, edition, pages
Elsevier, 2024
Keywords
Acylcarnitines, Colorectal cancer, Glycerophospholipids, Lipids, Metabolomics, Sphingolipids
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-222579 (URN)10.1016/j.ebiom.2024.105024 (DOI)38412638 (PubMedID)2-s2.0-85187658965 (Scopus ID)
Funder
World Cancer Research Fund International, 2013/1002EU, FP7, Seventh Framework Programme, 313010
Available from: 2024-04-08 Created: 2024-04-08 Last updated: 2024-04-12Bibliographically approved
Papadimitriou, N., Qu, C., Harrison, T. A., Bever, A. M., Martin, R. M., Tsilidis, K. K., . . . Murphy, N. (2024). Body size and risk of colorectal cancer molecular defined subtypes and pathways: mendelian randomization analyses. EBioMedicine, 101, Article ID 105010.
Open this publication in new window or tab >>Body size and risk of colorectal cancer molecular defined subtypes and pathways: mendelian randomization analyses
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2024 (English)In: EBioMedicine, E-ISSN 2352-3964, Vol. 101, article id 105010Article in journal (Refereed) Published
Abstract [en]

Background: Obesity has been positively associated with most molecular subtypes of colorectal cancer (CRC); however, the magnitude and the causality of these associations is uncertain.

Methods: We used Mendelian randomization (MR) to examine potential causal relationships between body size traits (body mass index [BMI], waist circumference, and body fat percentage) with risks of Jass classification types and individual subtypes of CRC (microsatellite instability [MSI] status, CpG island methylator phenotype [CIMP] status, BRAF and KRAS mutations). Summary data on tumour markers were obtained from two genetic consortia (CCFR, GECCO).

Findings: A 1-standard deviation (SD:5.1 kg/m2) increment in BMI levels was found to increase risks of Jass type 1MSI-high,CIMP-high,BRAF-mutated,KRAS-wildtype (odds ratio [OR]: 2.14, 95% confidence interval [CI]: 1.46, 3.13; p-value = 9 × 10−5) and Jass type 2non-MSI-high,CIMP-high,BRAF-mutated,KRAS-wildtype CRC (OR: 2.20, 95% CI: 1.26, 3.86; p-value = 0.005). The magnitude of these associations was stronger compared with Jass type 4non-MSI-high,CIMP-low/negative,BRAF-wildtype,KRAS-wildtype CRC (p-differences: 0.03 and 0.04, respectively). A 1-SD (SD:13.4 cm) increment in waist circumference increased risk of Jass type 3non-MSI-high,CIMP-low/negative,BRAF-wildtype,KRAS-mutated (OR 1.73, 95% CI: 1.34, 2.25; p-value = 9 × 10−5) that was stronger compared with Jass type 4 CRC (p-difference: 0.03). A higher body fat percentage (SD:8.5%) increased risk of Jass type 1 CRC (OR: 2.59, 95% CI: 1.49, 4.48; p-value = 0.001), which was greater than Jass type 4 CRC (p-difference: 0.03).

Interpretation: Body size was more strongly linked to the serrated (Jass types 1 and 2) and alternate (Jass type 3) pathways of colorectal carcinogenesis in comparison to the traditional pathway (Jass type 4).

Funding: Cancer Research UK, National Institute for Health Research, Medical Research Council, National Institutes of Health, National Cancer Institute, American Institute for Cancer Research, Brigham and Women's Hospital, Prevent Cancer Foundation, Victorian Cancer Agency, Swedish Research Council, Swedish Cancer Society, Region Västerbotten, Knut and Alice Wallenberg Foundation, Lion's Cancer Research Foundation, Insamlingsstiftelsen, Umeå University. Full funding details are provided in acknowledgements.

Place, publisher, year, edition, pages
Elsevier, 2024
Keywords
Colorectal cancer, Mendelian randomization, Molecular subtypes, Obesity
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-222809 (URN)10.1016/j.ebiom.2024.105010 (DOI)38350331 (PubMedID)2-s2.0-85184797654 (Scopus ID)
Funder
Swedish Research Council, VR 2017-00650Swedish Research Council, VR 2017-01737Knut and Alice Wallenberg Foundation, VLL-765961
Available from: 2024-04-11 Created: 2024-04-11 Last updated: 2024-04-11Bibliographically approved
Bodén, S., Zheng, R., Ribbenstedt, A., Landberg, R., Harlid, S., Vidman, L., . . . Brunius, C. (2024). Dietary patterns, untargeted metabolite profiles and their association with colorectal cancer risk. Scientific Reports, 14(1), Article ID 2244.
Open this publication in new window or tab >>Dietary patterns, untargeted metabolite profiles and their association with colorectal cancer risk
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2024 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 14, no 1, article id 2244Article in journal (Refereed) Published
Abstract [en]

We investigated data-driven and hypothesis-driven dietary patterns and their association to plasma metabolite profiles and subsequent colorectal cancer (CRC) risk in 680 CRC cases and individually matched controls. Dietary patterns were identified from combined exploratory/confirmatory factor analysis. We assessed association to LC–MS metabolic profiles by random forest regression and to CRC risk by multivariable conditional logistic regression. Principal component analysis was used on metabolite features selected to reflect dietary exposures. Component scores were associated to CRC risk and dietary exposures using partial Spearman correlation. We identified 12 data-driven dietary patterns, of which a breakfast food pattern showed an inverse association with CRC risk (OR per standard deviation increase 0.89, 95% CI 0.80–1.00, p = 0.04). This pattern was also inversely associated with risk of distal colon cancer (0.75, 0.61–0.96, p = 0.01) and was more pronounced in women (0.69, 0.49–0.96, p = 0.03). Associations between meat, fast-food, fruit soup/rice patterns and CRC risk were modified by tumor location in women. Alcohol as well as fruit and vegetables associated with metabolite profiles (Q2 0.22 and 0.26, respectively). One metabolite reflecting alcohol intake associated with increased CRC risk, whereas three metabolites reflecting fiber, wholegrain, and fruit and vegetables associated with decreased CRC risk.

Place, publisher, year, edition, pages
Springer Nature, 2024
National Category
Nutrition and Dietetics Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-220475 (URN)10.1038/s41598-023-50567-6 (DOI)001152222400046 ()38278865 (PubMedID)2-s2.0-85183347182 (Scopus ID)
Funder
Swedish Cancer SocietySwedish Research CouncilRegion VästerbottenIngaBritt and Arne Lundberg’s Research Foundation
Available from: 2024-02-16 Created: 2024-02-16 Last updated: 2024-02-16Bibliographically approved
Thomas, C. E., Georgeson, P., Qu, C., Steinfelder, R. S., Buchanan, D. D., Song, M., . . . Phipps, A. I. (2024). Epidemiologic factors in relation to colorectal cancer risk and survival by genotoxic colibactin mutational signature. Cancer Epidemiology, Biomarkers and Prevention, 33(4), 534-546
Open this publication in new window or tab >>Epidemiologic factors in relation to colorectal cancer risk and survival by genotoxic colibactin mutational signature
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2024 (English)In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 33, no 4, p. 534-546Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The genotoxin colibactin causes a tumor single-base substitution (SBS) mutational signature, SBS88. It is unknown whether epidemiologic factors' association with colorectal cancer risk and survival differs by SBS88.

METHODS: Within the Genetic Epidemiology of Colorectal Cancer Consortium and Colon Cancer Family Registry, we measured SBS88 in 4,308 microsatellite stable/microsatellite instability low tumors. Associations of epidemiologic factors with colorectal cancer risk by SBS88 were assessed using multinomial regression (N = 4,308 cases, 14,192 controls; cohort-only cases N = 1,911), and with colorectal cancer-specific survival using Cox proportional hazards regression (N = 3,465 cases).

RESULTS: 392 (9%) tumors were SBS88 positive. Among all cases, the highest quartile of fruit intake was associated with lower risk of SBS88-positive colorectal cancer than SBS88-negative colorectal cancer [odds ratio (OR) = 0.53, 95% confidence interval (CI) 0.37-0.76; OR = 0.75, 95% CI 0.66-0.85, respectively, Pheterogeneity = 0.047]. Among cohort studies, associations of body mass index (BMI), alcohol, and fruit intake with colorectal cancer risk differed by SBS88. BMI ≥30 kg/m2 was associated with worse colorectal cancer-specific survival among those SBS88-positive [hazard ratio (HR) = 3.40, 95% CI 1.47-7.84], but not among those SBS88-negative (HR = 0.97, 95% CI 0.78-1.21, Pheterogeneity = 0.066).

CONCLUSIONS: Most epidemiologic factors did not differ by SBS88 for colorectal cancer risk or survival. Higher BMI may be associated with worse colorectal cancer-specific survival among those SBS88-positive; however, validation is needed in samples with whole-genome or whole-exome sequencing available.

IMPACT: This study highlights the importance of identification of tumor phenotypes related to colorectal cancer and understanding potential heterogeneity for risk and survival.

Place, publisher, year, edition, pages
American Association For Cancer Research (AACR), 2024
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-223486 (URN)10.1158/1055-9965.EPI-23-0600 (DOI)001201762900002 ()38252034 (PubMedID)2-s2.0-85189863522 (Scopus ID)
Funder
Swedish Cancer Society
Available from: 2024-04-19 Created: 2024-04-19 Last updated: 2024-04-19Bibliographically approved
Tian, Y., Lin, Y., Qu, C., Arndt, V., Baurley, J. W., Berndt, S. I., . . . Chang-Claude, J. (2024). Genetic risk impacts the association of menopausal hormone therapy with colorectal cancer risk. British Journal of Cancer
Open this publication in new window or tab >>Genetic risk impacts the association of menopausal hormone therapy with colorectal cancer risk
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2024 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827Article in journal (Refereed) Epub ahead of print
Abstract [en]

Background: Menopausal hormone therapy (MHT), a common treatment to relieve symptoms of menopause, is associated with a lower risk of colorectal cancer (CRC). To inform CRC risk prediction and MHT risk-benefit assessment, we aimed to evaluate the joint association of a polygenic risk score (PRS) for CRC and MHT on CRC risk.

Methods: We used data from 28,486 postmenopausal women (11,519 cases and 16,967 controls) of European descent. A PRS based on 141 CRC-associated genetic variants was modeled as a categorical variable in quartiles. Multiplicative interaction between PRS and MHT use was evaluated using logistic regression. Additive interaction was measured using the relative excess risk due to interaction (RERI). 30-year cumulative risks of CRC for 50-year-old women according to MHT use and PRS were calculated.

Results: The reduction in odds ratios by MHT use was larger in women within the highest quartile of PRS compared to that in women within the lowest quartile of PRS (p-value = 2.7 × 10−8). At the highest quartile of PRS, the 30-year CRC risk was statistically significantly lower for women taking any MHT than for women not taking any MHT, 3.7% (3.3%–4.0%) vs 6.1% (5.7%–6.5%) (difference 2.4%, P-value = 1.83 × 10−14); these differences were also statistically significant but smaller in magnitude in the lowest PRS quartile, 1.6% (1.4%–1.8%) vs 2.2% (1.9%–2.4%) (difference 0.6%, P-value = 1.01 × 10−3), indicating 4 times greater reduction in absolute risk associated with any MHT use in the highest compared to the lowest quartile of genetic CRC risk.

Conclusions: MHT use has a greater impact on the reduction of CRC risk for women at higher genetic risk. These findings have implications for the development of risk prediction models for CRC and potentially for the consideration of genetic information in the risk-benefit assessment of MHT use.

Place, publisher, year, edition, pages
Springer Nature, 2024
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-223079 (URN)10.1038/s41416-024-02638-2 (DOI)001195111400001 ()38561434 (PubMedID)2-s2.0-85189134864 (Scopus ID)
Funder
NIH (National Institutes of Health)
Available from: 2024-04-17 Created: 2024-04-17 Last updated: 2024-04-17
Aglago, E. K., Kim, A., Lin, Y., Qu, C., Evangelou, M., Ren, Y., . . . Campbell, P. T. (2023). A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk. Cancer Research, 83(15), 2572-2583
Open this publication in new window or tab >>A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk
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2023 (English)In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 83, no 15, p. 2572-2583Article in journal (Refereed) Published
Abstract [en]

Colorectal cancer risk can be impacted by genetic, environmental, and lifestyle factors, including diet and obesity. Gene-environment interactions (G × E) can provide biological insights into the effects of obesity on colorectal cancer risk. Here, we assessed potential genome-wide G × E interactions between body mass index (BMI) and common SNPs for colorectal cancer risk using data from 36,415 colorectal cancer cases and 48,451 controls from three international colorectal cancer consortia (CCFR, CORECT, and GECCO). The G × E tests included the conventional logistic regression using multiplicative terms (one degree of freedom, 1DF test), the two-step EDGE method, and the joint 3DF test, each of which is powerful for detecting G × E interactions under specific conditions. BMI was associated with higher colorectal cancer risk. The two-step approach revealed a statistically significant G×BMI interaction located within the Formin 1/Gremlin 1 (FMN1/GREM1) gene region (rs58349661). This SNP was also identified by the 3DF test, with a suggestive statistical significance in the 1DF test. Among participants with the CC genotype of rs58349661, overweight and obesity categories were associated with higher colorectal cancer risk, whereas null associations were observed across BMI categories in those with the TT genotype. Using data from three large international consortia, this study discovered a locus in the FMN1/GREM1 gene region that interacts with BMI on the association with colorectal cancer risk. Further studies should examine the potential mechanisms through which this locus modifies the etiologic link between obesity and colorectal cancer.

SIGNIFICANCE: This gene-environment interaction analysis revealed a genetic locus in FMN1/GREM1 that interacts with body mass index in colorectal cancer risk, suggesting potential implications for precision prevention strategies.

Place, publisher, year, edition, pages
American Association For Cancer Research (AACR), 2023
National Category
Medical Genetics
Identifiers
urn:nbn:se:umu:diva-212758 (URN)10.1158/0008-5472.CAN-22-3713 (DOI)37249599 (PubMedID)2-s2.0-85166391630 (Scopus ID)
Available from: 2023-08-10 Created: 2023-08-10 Last updated: 2023-08-10Bibliographically approved
Harbs, J., Rinaldi, S., Keski-Rahkonen, P., Liu, X., Palmqvist, R., van Guelpen, B. & Harlid, S. (2023). An epigenome-wide analysis of sex hormone levels and DNA methylation in male blood samples. Epigenetics, 18(1), Article ID 2196759.
Open this publication in new window or tab >>An epigenome-wide analysis of sex hormone levels and DNA methylation in male blood samples
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2023 (English)In: Epigenetics, ISSN 1559-2294, E-ISSN 1559-2308, Vol. 18, no 1, article id 2196759Article in journal (Refereed) Published
Abstract [en]

Endogenous sex hormones and DNA methylation both play important roles in various diseases. However, their interplay is largely unknown. A deeper understanding of their interrelationships could provide new insights into the pathology of disease development. We, therefore, investigated associations between circulating sex hormones, sex hormone binding globulin (SHBG), and DNA methylation in blood, using samples from 77 men (65 with repeated samples), from the population-based Northern Sweden Health and Disease Study (NSHDS). DNA methylation was measured in buffy coat using the Infinium Methylation EPIC BeadChip (Illumina). Sex hormone (oestradiol, oestrone, testosterone, androstenedione, dehydroepiandrosterone, and progesterone) and SHBG concentrations were measured in plasma using a high-performance liquid chromatography tandem mass spectrometry (LC/MS-MS) method and an enzyme-linked immunoassay, respectively. Associations between sex hormones, SHBG, and DNA methylation were estimated using both linear regression and mixed-effects models. Additionally, we used the comb-p method to identify differentially methylated regions based on nearby P values. We identified one novel CpG site (cg14319657), at which DNA methylation was associated with dehydroepiandrosterone, surpassing a genome-wide significance level. In addition, more than 40 differentially methylated regions were associated with levels of sex hormones and SHBG and several of these mapped to genes involved in hormone-related diseases. Our findings support a relationship between circulating sex hormones and DNA methylation and suggest that further investigation is warranted, both for validation, further exploration and to gain a deeper understanding of the mechanisms and potential consequences for health and disease.

Place, publisher, year, edition, pages
Taylor & Francis Group, 2023
Keywords
Sex hormones, sex hormone binding globulin, DNA methylation, men, NSHDS
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-205420 (URN)10.1080/15592294.2023.2196759 (DOI)000961068800001 ()36994855 (PubMedID)2-s2.0-85151198554 (Scopus ID)
Funder
Cancerforskningsfonden i Norrland, AMP 17-866Cancerforskningsfonden i Norrland, AMP 17-856Cancerforskningsfonden i Norrland, AMP 18-915Cancerforskningsfonden i Norrland, AMP 19-967Region Västerbotten, VLL-547711Region Västerbotten, VLL-680921Region Västerbotten, VLL58269Umeå University
Note

Originally included in thesis in manuscript form. 

Available from: 2023-03-06 Created: 2023-03-06 Last updated: 2023-09-05Bibliographically approved
Renman, D., van Guelpen, B., Anderson, F., Axelsson, J., Riklund, K., Strigård, K., . . . Gylling, B. (2023). Association of pre-diagnostic physical exercise and peri-diagnostic body composition with mortality in non-metastatic colorectal cancer. International Journal of Colorectal Disease, 38(1), Article ID 239.
Open this publication in new window or tab >>Association of pre-diagnostic physical exercise and peri-diagnostic body composition with mortality in non-metastatic colorectal cancer
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2023 (English)In: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 38, no 1, article id 239Article in journal (Refereed) Published
Abstract [en]

Purpose: Sarcopenia and myosteatosis, quantified via computed tomography (CT), are associated with poor colorectal cancer outcomes. These body composition estimates can be influenced by physical exercise. We explored the correlation between pre-diagnostic physical exercise, body composition close to diagnosis, and the combined prognosis impact of these factors.

Methods: We studied 519 stage I–III colorectal cancer (CRC) cases diagnosed 2000–2016 with pre-diagnostic self-reported recreational physical exercise data collected in the prospective, population-based Northern Sweden Health and Disease Study, and CT-estimated skeletal muscle index (SMI) or skeletal muscle density (SMD). Risk estimates were calculated by multivariable logistic regression and Cox proportional hazards models.

Results: No association was seen between low pre-diagnostic physical exercise and sarcopenia/myosteatosis in the multivariable model adjusted for age, sex, educational level, tumor stage, and tumor location. In multivariable Cox regression models, the combination of low pre-diagnostic physical exercise and either sarcopenia or myosteatosis at the time of diagnosis was associated with cancer-specific mortality compared to the reference group of high physical exercise combined with no sarcopenia/myosteatosis (adjusted HR 1.94 95% CI 1.00–3.76 for sarcopenia and adjusted HR 2.39 95% CI 1.16–4.94 for myosteatosis).

Conclusions: The combined presence of low pre-diagnostic physical exercise and sarcopenia or myosteatosis was associated with increased CRC-specific mortality. Despite the positive effect on prognosis, physical exercise did not alter body composition estimates at diagnosis, which could indicate attenuation from other factors.

Place, publisher, year, edition, pages
Springer Nature, 2023
Keywords
Colorectal cancer, Exercise, Myosteatosis, Physical activity, Sarcopenia
National Category
Cancer and Oncology Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-215081 (URN)10.1007/s00384-023-04536-0 (DOI)37755537 (PubMedID)2-s2.0-85172659066 (Scopus ID)
Funder
Cancerforskningsfonden i Norrland, AMP 20-999Visare Norr, 967732Region Västerbotten, ALF RV-968855Region Västerbotten, ALF RV-982739
Available from: 2023-10-13 Created: 2023-10-13 Last updated: 2024-02-08Bibliographically approved
Rothwell, J. A., Bešević, J., Dimou, N., Breeur, M., Murphy, N., Jenab, M., . . . Gunter, M. J. (2023). Circulating amino acid levels and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition and UK Biobank cohorts. BMC Medicine, 21(1), Article ID 80.
Open this publication in new window or tab >>Circulating amino acid levels and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition and UK Biobank cohorts
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2023 (English)In: BMC Medicine, E-ISSN 1741-7015, Vol. 21, no 1, article id 80Article in journal (Refereed) Published
Abstract [en]

Background: Amino acid metabolism is dysregulated in colorectal cancer patients; however, it is not clear whether pre-diagnostic levels of amino acids are associated with subsequent risk of colorectal cancer. We investigated circulating levels of amino acids in relation to colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) and UK Biobank cohorts.

Methods: Concentrations of 13-21 amino acids were determined in baseline fasting plasma or serum samples in 654 incident colorectal cancer cases and 654 matched controls in EPIC. Amino acids associated with colorectal cancer risk following adjustment for the false discovery rate (FDR) were then tested for associations in the UK Biobank, for which measurements of 9 amino acids were available in 111,323 participants, of which 1221 were incident colorectal cancer cases.

Results: Histidine levels were inversely associated with colorectal cancer risk in EPIC (odds ratio [OR] 0.80 per standard deviation [SD], 95% confidence interval [CI] 0.69–0.92, FDR P-value=0.03) and in UK Biobank (HR 0.93 per SD, 95% CI 0.87–0.99, P-value=0.03). Glutamine levels were borderline inversely associated with colorectal cancer risk in EPIC (OR 0.85 per SD, 95% CI 0.75–0.97, FDR P-value=0.08) and similarly in UK Biobank (HR 0.95, 95% CI 0.89–1.01, P=0.09) In both cohorts, associations changed only minimally when cases diagnosed within 2 or 5 years of follow-up were excluded.

Conclusions: Higher circulating levels of histidine were associated with a lower risk of colorectal cancer in two large prospective cohorts. Further research to ascertain the role of histidine metabolism and potentially that of glutamine in colorectal cancer development is warranted.

Place, publisher, year, edition, pages
BioMed Central (BMC), 2023
Keywords
Amino acids, Colorectal cancer, Glutamine, Histidine
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-205643 (URN)10.1186/s12916-023-02739-4 (DOI)000940903600001 ()36855092 (PubMedID)2-s2.0-85149153333 (Scopus ID)
Available from: 2023-03-14 Created: 2023-03-14 Last updated: 2023-09-05Bibliographically approved
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Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-9692-101X

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