Lifestyle Behaviors and Inflammatory Markers in Childhood Cancer Survivors: a systematic review
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Background: Survivors of childhood-, adolescent- and young adult (CAYA) cancers often face comorbidities such as cardiovascular disease and osteoporosis earlier than expected for their age. These observed effects have previously been linked to a cancer treatment-induced pro-inflammatory state. As these late effects can greatly impact mortality and quality of life, it is important to identify factors or interventions that can delay the onset of these diseases. Previous research has shown that a poor lifestyle is a modifiable risk factor for inflammation. Consequently, healthy lifestyle choices might counteract the inflammatory processes that underly the late effects in survivors. Aim: The aim of this systematic review was to give an overview of the evidence for the relationship between lifestyle behaviors and inflammatory markers in CAYA cancer survivors. Methods: For this systematic review, the database PubMed was searched for articles reporting lifestyle behaviors and inflammatory markers (acute phase proteins) in CAYA cancer survivors (0-25 years at diagnosis). Lifestyle behaviors were defined as dietary intake, physical activity, vitamin D levels or intake, alcohol intake, smoking and stress (therapy). Titles and abstracts were screened by two independent reviewers and eligible studies were selected for full-text review. From all included study, we extracted data concerning study methods, characteristics of participants and outcomes along with risk of bias. Results: In total, 722 studies were screened of which two studies were included in this review. The first study by Blair and colleagues was a randomized cross-over trial, investigating the effect of 4-week purple grape juice (pGJ) supplementation compared to 4-week clear apple juice (cAJ) supplementation on plasma inflammatory markers Myeloperoxidase (MPO) and high sensitivity C-reactive protein (hs-CRP) in survivors of various childhood cancers. There was no significant beneficial effect of pGJ- over cAJ supplementation on MPO (p=0.15) or hs-CRP (p=0.37) levels. The second study by Ketterl and colleagues had an observational cross-sectional design, investigating the inflammatory markers Interleukin (IL)-6 and tumor necrosis factor (TNF)-α, and body composition measures (percent fat mass (PFM) and total lean body mass (LBM)) in survivors of hematopoietic cell transplantation (HCT) compared to age- and sex-matched siblings. HCT survivors had significantly higher IL-6 levels (p<0.05) and approximately 5% higher PFM (p<0.005) compared to their siblings, irrespective of previous cancer treatment. Additionally, LBM was significantly lower in HCT survivors who had received Total Body Irradiation (TBI) (p<0.001). Discussion & Conclusion: The included studies suggested that although pGJ supplementation does not change inflammatory markers, low lean body mass or increased PFM might be associated with chronic inflammation and might therefore be a target for delaying late effects in childhood cancer survivors. In adult cancer survivors, lifestyle has already shown beneficial effects in inflammation and chronic diseases, which highlights the need for randomized trials investigating the relation between lifestyle, inflammation, and late effects in childhood cancer survivors.