Genetically Predicted Calorie Dietary Preference as a Causal Risk Factor for Multiple Cancer Types: Evidence from Mendelian Randomization

Background There is evidence that diet and nutrition are modifiable risk factors for several cancers. however, the causal impact of dietary calorie preference on cancer development remains uncertain. Methods In this study, data on dietary calorie preference were sourced from a large-scale genome-wide association study (GWAS) database of food liking, while information on 18 cancer types was obtained from Finger R9 database. Two-sample Mendelian randomization (MR) analysis was conducted to assess the causal effects of Calorie Dietary Liking on 18 types of cancers. The inverse variance weighting (IVW) method was the primary analytical approach, with significant correlations further examined using Egger regression, MR-PRESSO, and weighted median methods. Results Our analyses revealed that a genetically predicted preference for high-calorie diets significantly raised the risk of non-Hodgkin lymphoma (NHL) (OR = 1.75, P  = 0.006), non-small cell lung cancer (NSCLC) (OR = 1.39, P  = 0.001), hepatocellular carcinoma (HCC) (OR = 2.06, P  = 0.025), and gastric cancer (GC) (OR = 1.47, P  = 0.012). Further subgroup analyses confirmed that high-calorie foods, particularly cheese liking, were strongly linked to an elevated HCC risk (OR = 2.43, P  = 0.000), while deep-fried food liking were associated with increased NSCLC risk (OR = 1.26, P  = 0.005). Low-calorie dietary liking showed causal association with the risk of prostate cancer (PCa) (OR = 0.85, P  = 0.013). Conclusion This comprehensive MR analysis suggested that genetically predicted high-calorie food liking, as well as its subgroups, may be a risk factor in the development of NHL, NSCLC, HCC, and GC. A low-calorie diet may have a protective effect on the risk of PCa.