Abstract 2318: Waist circumference and the risk of cancer: Two-sample mendelian randomization

Abstract Background: The normal range of waist circumference for Asians is less than 90 cm for men and less than 85 cm for women, according to the Korean Society for the Study of Obesity (KSSO) guidelines. While observational studies have suggested an association between obesity and cancer, the causality of obesity in cancer development is not fully established. A two-sample Mendelian randomization (MR) analysis was used to assess whether a genetic predisposition index for waist circumference (WC) was associated with overall cancer and 10 site-specific cancer risk.While observational studies have suggested an association between obesity and cancer, the causality of obesity in cancer development is not fully established. A two-sample Mendelian randomization (MR) analysis was used to assess whether a genetic predisposition index for waist circumference (WC) was associated with overall cancer and 10 site-specific cancer risk. Methods: The MR method can assess potential causal relationships in various diseases. Summary-level data for WC were extracted from The Korean Cancer Prevention Study-II (KCPS-II) Biobank, and summary-level data for cancer were extracted from The Korean Genome Epidemiology Study (KoGES). Results: There was no causal relationship between WC and total cancer, but a positive correlation was found in colorectal cancer and thyroid cancer (total cancer OR=1.009, 95% CI=0.995-1.023; colorectal cancer OR=1.051, 95% CI=1.011-1.091; thyroid cancer OR=1.037, 95% CI=1.006-1.068). In cervical cancer and prostate cancer, protective results were shown for WC (cervical cancer OR=0.943, 95% CI=0.891-0.998; prostate cancer OR=0.874, 95% CI=0.766-0.998). Conclusion: The evidence supporting a causal relationship between WC and cancer was limited. Genetically predicted WC was positively correlated with colorectal cancer and thyroid cancer. The current study found causal detrimental effects of WC on several cancers. We propose to strengthen cancer screening in patients with large WC to enable early detection of cancer. Citation Format: Su Hyun Lee, Sun Ha Jee, Yoon-Jung Choi. Waist circumference and the risk of cancer: Two-sample mendelian randomization [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2318.