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

**Authors:** Zheng Xu, Xiaoru Luo, Wuliang Diao, Xinlinzi Tang, Yue Zhang, Jiahao Wang, Zichao Jiang, Ting Lei

PMC · DOI: 10.1093/oncolo/oyaf369 · 2025-11-05

## TL;DR

This study finds that sarcopenia, or muscle loss, is linked to a higher risk of developing certain cancers and may play a causal role in cancer development.

## Contribution

The study provides novel evidence using NHANES data and Mendelian randomization to show a causal link between sarcopenia and cancer occurrence.

## Key findings

- Lower lean mass and sarcopenia were associated with increased cancer risk, especially in individuals over 40.
- Mendelian randomization confirmed a causal negative effect of appendicular lean mass on overall cancer types.
- Sarcopenia was specifically linked to higher risks of colon, ovarian, uterine, and certain blood cancers.

## Abstract

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.

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.

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.

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.

Graphical Abstract

## Linked entities

- **Diseases:** cancer (MONDO:0004992), colon cancer (MONDO:0002032), ovarian cancer (MONDO:0005140), uterine cancer (MONDO:0002715), lymphoid leukemia (MONDO:0005402), breast cancer (MONDO:0004989)

## Full-text entities

- **Diseases:** lymphoid leukemia (MESH:D007945), breast cancer (MESH:D001943), muscle condition (MESH:D009135), cancer (MESH:D009369), Sarcopenia (MESH:D055948), muscle (MESH:D019042), colon, ovarian, and uterine cancers (MESH:D010051)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12628308/full.md

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Source: https://tomesphere.com/paper/PMC12628308