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Plasma concentrations of gut hormones acyl ghrelin and peptide YY and subsequent risk of colorectal cancer and molecular tumor subtypes
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.ORCID iD: 0000-0002-8958-975x
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.ORCID iD: 0000-0002-4759-2643
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
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2023 (English)In: Cancer Prevention Research, ISSN 1940-6207, E-ISSN 1940-6215, Vol. 16, no 2, p. 75-87Article in journal (Refereed) Published
Abstract [en]

Obesity and metabolic dysfunction are implicated in colorectal cancer development. Appetite-regulating gut hormones might have a role in colorectal cancer risk. We investigated whether circulating levels of the gut hormones ghrelin (analyzed as acyl ghrelin) and Peptide YY (PYY) were associated with subsequent colorectal cancer risk, including clinical and molecular tumor subtypes. We also provide descriptive data on these hormones in relation to background participant characteristics and metabolic biomarkers. This population-based study included 1,010 matched case-control pairs with a median of 12.3 years of follow-up. Acyl ghrelin and PYY were measured by multiplex immunoassay. Data on KRAS and BRAF mutations and microsatellite instability (MSI) status were available for 704 and 708 cases, respectively. Conditional logistic regression models estimated association to colorectal cancer risk. Partial correlation and linear regression were used to investigate relationships between background and metabolic variables and variation in plasma gut hormone concentrations. Acyl ghrelin was not clearly associated with colorectal cancer risk (multivariable OR per 1 SD increase: 1.11; 95% CI, 1.00-1.23). Positive associations were observed for specific subtypes, in particular BRAF-mutated colorectal cancer and right-sided colon cancer, although with nonsignificant heterogeneity. PYY was not related to colorectal cancer risk (multivariable OR per 1 SD: 1.04; 95% CI, 0.95-1.14) or any tumor subtype. In the control participants, ghrelin was inversely correlated with BMI, and PYY was positively correlated with C-peptide and insulin levels. These findings provide limited support for a possible role for ghrelin in colorectal cancer development, primarily in specific anatomical and molecular tumor subtypes.

PREVENTION RELEVANCE: The findings of this study do not support a major role for the metabolic gut hormones ghrelin and PYY in colorectal cancer development but suggest the possibility of an involvement for ghrelin in specific tumor subtypes. Elucidating subtype-specific risk factors and mechanisms of carcinogenesis may have implications for precision prevention.

Place, publisher, year, edition, pages
American Association for Cancer Research , 2023. Vol. 16, no 2, p. 75-87
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:umu:diva-204740DOI: 10.1158/1940-6207.CAPR-22-0325ISI: 000928164800001PubMedID: 36367526Scopus ID: 2-s2.0-85147457884OAI: oai:DiVA.org:umu-204740DiVA, id: diva2:1738578
Funder
Region VästerbottenUmeå UniversitySwedish Cancer Society, 2017/ 581Swedish Cancer Society, 2014/780Swedish Cancer Society, 2012/0501Cancerforskningsfonden i Norrland, AMP 21-1039Cancerforskningsfonden i Norrland, AMP 20-1015Cancerforskningsfonden i Norrland, AMP 19-984Knut and Alice Wallenberg FoundationAvailable from: 2023-02-22 Created: 2023-02-22 Last updated: 2023-09-05Bibliographically approved

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Bodén, StinaHarbs, JustinSundkvist, AnneliMyte, RobinGylling, BjörnZingmark, CarlLöfgren Burström, AnnaPalmqvist, RichardHarlid, Sophiavan Guelpen, Bethany

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Bodén, StinaHarbs, JustinSundkvist, AnneliMyte, RobinGylling, BjörnZingmark, CarlLöfgren Burström, AnnaPalmqvist, RichardHarlid, Sophiavan Guelpen, Bethany
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