Circulating metabolome landscape in Lynch syndrome

Tiina A Jokela; Jari E Karppinen; Minta Kärkkäinen; Jukka-Pekka Mecklin; Simon Walker; Toni T Seppälä; Eija K Laakkonen

doi:10.1186/s40170-024-00331-9

Circulating metabolome landscape in Lynch syndrome

Cancer Metab. 2024 Feb 5;12(1):4. doi: 10.1186/s40170-024-00331-9.

Authors

Tiina A Jokela¹, Jari E Karppinen^{2

3}, Minta Kärkkäinen², Jukka-Pekka Mecklin^{4

5}, Simon Walker⁵, Toni T Seppälä^{6

7

8

9}, Eija K Laakkonen²

Affiliations

¹ Gerontology Research Center and Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland. tiina.a.jokela@jyu.fi.
² Gerontology Research Center and Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland.
³ Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
⁴ Department of Surgery, The Wellbeing Services County of Central Finland, Jyväskylä, Finland.
⁵ Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland.
⁶ Department of Clinical Medicine, Faculty of Medicine and Health Technology, University of Tampere, Tampere, Finland.
⁷ Applied Tumor Genomics Research Program, Research Programs Unit, University of Helsinki, Helsinki, Finland.
⁸ Department of Abdominal Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
⁹ Department of Gastroenterology and Alimentary Tract Surgery and TAYS Cancer Centre, Tampere University Hospital, Tampere, Finland.

Abstract

Circulating metabolites systemically reflect cellular processes and can modulate the tissue microenvironment in complex ways, potentially impacting cancer initiation processes. Genetic background increases cancer risk in individuals with Lynch syndrome; however, not all carriers develop cancer. Various lifestyle factors can influence Lynch syndrome cancer risk, and lifestyle choices actively shape systemic metabolism, with circulating metabolites potentially serving as the mechanical link between lifestyle and cancer risk. This study aims to characterize the circulating metabolome of Lynch syndrome carriers, shedding light on the energy metabolism status in this cancer predisposition syndrome.This study consists of a three-group cross-sectional analysis to compare the circulating metabolome of cancer-free Lynch syndrome carriers, sporadic colorectal cancer (CRC) patients, and healthy non-carrier controls. We detected elevated levels of circulating cholesterol, lipids, and lipoproteins in LS carriers. Furthermore, we unveiled that Lynch syndrome carriers and CRC patients displayed similar alterations compared to healthy non-carriers in circulating amino acid and ketone body profiles. Overall, cancer-free Lynch syndrome carriers showed a unique circulating metabolome landscape.This study provides valuable insights into the systemic metabolic landscape of Lynch syndrome individuals. The findings hint at shared metabolic patterns between cancer-free Lynch syndrome carriers and CRC patients.

Keywords: Cholesterol metabolism; Circulating amino acids; DNA mismatch repair deficiency; GlycA; Hereditary cancer; Ketone bodies; Lipid metabolism; Metabolomic biomarkers.

Abstract

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