Pilot Study on Malnutrition and DNA Damage in Patients with Newly Diagnosed Gastrointestinal Tumors: Is DNA Damage Reversible by Early Individualized Nutritional Support?

Background And Aims: Nutritional support (NS) in patients with malignancies and malnutrition improves outcome and treatment tolerance. The underlying mechanisms are not completely understood. We aimed to investigate for the first time the influence of an early individualized NS in newly diagnosed patients with gastrointestinal/hepato-pancreatic malignancies and malnutrition on DNA damage, oxidative stress and subclinical inflammation.

Methods: This prospective case-control study included 43 patients with newly diagnosed malignancies and malnutrition. At baseline (F0), we documented patients' data, oncological diagnosis, comorbidities, alcohol/ nicotine consume. Nutritional parameters, DNA damage [histone-variant H2AX phosphorylated on the 139-serine residue (γ-H2AX) foci/cell], oxidative status, subclinical inflammation were measured. During diagnostic workup, patients received an individualized NS, and got a follow-up before the start of treatment (F1), (n=21). Healthy controls (n=21) were included for comparison of DNA damage at baseline.

Results: γ-H2AX-values at baseline were higher than in controls (p<0.001) and higher than after the NS at F1 (p=0.011). Patients with severe gastrointestinal symptoms (SGS) had higher baseline foci compared to patients with mild gastrointestinal symptoms (MGS) at F0 (p<0.001) and showed a stronger decrease of DNA damage under NS (p=0.002). Laboratory data were stable, with tendential reduction in oxidative stress, without progression of subclinical inflammation. The number of γ-H2AX foci did not differ among patients divided by sex, age, nicotine or alcohol intake or the presence of distant metastases.

Conclusion: Increased baseline DNA damage in patients with newly diagnosed tumors and malnutrition decreased under pretherapeutic NS, independent of other known genotoxic factors. This contributes towards understanding the positive effects of early NS in cancer management.