Contributing effects of sarcopenia on cancer occurrence: novel evidence based on NHANES 1999-2020 and two-sample mendelian randomization study.

BACKGROUND: Sarcopenia is associated with worse prognosis in patients with cancer, and patients with cancer usually have poor muscle condition. However, it is still not clear whether sarcopenia contributes to cancer occurrence. METHODS: This study utilized data from the National Health and Nutrition Examination Survey (NHANES) 1999-2020 to assess the relationship between sarcopenia and cancer. Key sarcopenia indicators, including lean mass measurements and sarcopenia diagnosed by European Working Group on Sarcopenia in Older People (EWGSOP) or Foundation for the National Institutes of Health (FNIH) criteria, were analyzed using quantile logistic regression models. A two-sample Mendelian Randomization (MR) approach was employed to explore the causal link between sarcopenia and cancer, leveraging genetic variants as instrumental variables. RESULTS: We found that after adjusting covariates, left arm lean mass, left leg lean mass and appendicular lean mass (ALM) were found to have significant negative influences on the occurrence of overall-cancer types, particularly in individuals over 40 years old. Sarcopenia (FNIH) significantly increased the risk of overall-cancer types, especially colon, ovarian, and uterine cancers. Smooth curve fitting showed that cancer incidence decreased with increasing muscle mass. MR analysis confirmed that ALM and whole body lean mass (WBLM) had causally negative effects on cancer, while grip strength and sarcopenia (by EWGSOP/FNIH criteria) demonstrated significant causal effects on specific cancer types, including lymphoid hematopoietic cancer, lymphoid leukemia, and breast cancer. CONCLUSION: Sarcopenia significantly impacts the incidence of various cancers and may causally contribute to cancer development. Managing sarcopenia could potentially benefit cancer prevention and treatment strategies.