Obesity, Central Adiposity, and Carcinogenesis: A Secondary Data Analysis of Cohort, Meta-Analytic, and Mendelian Randomization Evidence
Keywords:
Obesity; Carcinogenesis; Body mass index (BMI); Central adiposity; Waist circumference; Waist–hip ratio; Endometrial cancer; Colorectal cancer; Mendelian randomization; Secondary data analysis.Abstract
Background: Obesity is a growing global epidemic and an established determinant of several malignancies. While general adiposity measured by body mass index (BMI) is widely studied, emerging evidence highlights the independent role of central adiposity in carcinogenesis.
Methods: We conducted a secondary analysis of published large-scale cohort studies, systematic reviews, meta-analyses, and Mendelian randomization (MR) reports. Data were harmonized across studies, and effect estimates were synthesized for BMI, waist circumference (WC), and waist–hip ratio (WHR) in relation to incident cancers. Results were summarized in tables and visualized using forest plots, spline dose–response curves, central adiposity comparisons, population attributable fractions (PAFs), and MR scatter plots.
Results: Elevated BMI was consistently associated with increased risk of endometrial (HR ~1.58), kidney (HR ~1.22), liver (HR ~1.17), gallbladder (HR ~1.28), and colorectal cancer (HR ~1.11). Weaker but significant associations were observed for ovarian and postmenopausal breast cancer, whereas premenopausal breast cancer showed an inverse association. Central adiposity, measured by WC and WHR, predicted cancer risk beyond BMI, particularly for colorectal and postmenopausal breast cancers. Subgroup analyses revealed stronger associations in men for colorectal and liver cancer, and in postmenopausal women for breast cancer. Sensitivity analyses excluding early follow-up, smokers, and diabetic participants confirmed robustness of findings. PAFs suggested that obesity may account for ~35% of endometrial cancers and 6–12% of colorectal, kidney, liver, and breast cancers. MR analyses demonstrated that genetically proxied adiposity increases colorectal and endometrial cancer risk, supporting a causal relationship.
Conclusion: This secondary data synthesis confirms that both general and central adiposity are causally associated with elevated cancer risk, with sex- and site-specific heterogeneity. Obesity prevention and waist circumference reduction represent critical strategies for reducing the global cancer burden.
