Causal relationship of sugar-sweetened and sweet beverages with colorectal cancer: a Mendelian randomization study

Prospective cohort studies have suggested that sugar-sweetened beverages (SSBs) intake is significantly associated with the risk of colorectal cancer (CRC). However, it remains unclear whether this observed association was susceptible to potential confounding factors due to the long-term development process of CRC, and the risk of CRC associated with sweet beverages has rarely been reported. We aimed to investigate the association between SSBs/sweet beverages and CRC risk.

We performed two-sample Mendelian randomization (MR) analysis using independent genetic variants for SSBs and sweet beverages from a published genome-wide association study (GWAS). Summary statistics for instrument-outcome associations from two databases for malignant neoplasms of the colon and the rectum (FinnGen and UK Biobank). The inverse weighted method (IVW) meta-analysis was the main method used to estimate the relationship, and sensitivity analyses were performed with Cochran's Q test, leave-one-out analysis, MR-Egger regression, Steiger filtering, and the MR PRESSO test.

Genetically predicted SSBs intake was associated with a higher colonic malignant neoplasms risk (odds ratio (OR): 1.013; 95% confidence interval (CI) 1.001, 1.026; P = 0.036) in a combined sample size of 579,986 individuals (4029 cases). Such a significant causal effect of SSBs on rectal malignant neoplasms or sweet beverages on CRC was not observed.

Our findings corroborated a causal association between SSBs and colonic malignant neoplasms risk but did not support such a relationship in the analysis of the rectal malignant neoplasms nor the sweet beverage intake, which might be interpreted with caution and further confirmed.