Affiliation:
1. Seoul National University College of Medicine
2. Seoul National University Graduate School
Abstract
Abstract
Background
Effects of confounders on associations between diet and colorectal cancer (CRC) in observational studies can be minimized in Mendelian randomization (MR) approach. This study aimed to investigate observational and genetically predicted associations between dietary intake and CRC using one-sample MR.
Methods
Using genetic data of over 93 million variants, we performed a genome-wide association study to find genomic risk loci associated with dietary intake in participants from the UK Biobank. Then we calculated genetic risk scores of diet-related variants and used them as instrumental variables in the two-stage least square MR framework to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for associations. We also performed observational analyses using age as a time-scale in Cox proportional hazard models.
Results
Allele scores were calculated from 399 genetic variants associated with the consumption of of red meat, processed meat, poultry, fish, milk, cheese, fruits, vegetables, coffee, tea, and alcohol in participants from the UK Biobank. In MR analysis, genetically predicted fruit intake was significantly associated with a 21% decreased risk of CRC (HR = 0.79, 95% CI = 0.66–0.95), and there was a marginally inverse association between vegetable intake and CRC (HR = 0.85, 95% CI = 0.71–1.02). Weaker associations were observed in multivariable analysis, with HRs (95% CIs) of 0.99 (0.98–1.01) and 0.99 (0.98-1.00) per increment of daily servings of fruits and vegetables, respectively.
Conclusion
Dietary habits were attributable to genetic variations, which can be used as instrumental variables in the MR framework. Our study supported a causal relationship between fruit intake and a decreased risk of CRC and suggested an effective strategy of consuming fruits in the primary prevention of CRC.
Publisher
Research Square Platform LLC
Reference55 articles.
1. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries;Sung H;CA Cancer J Clin,2021
2. The World Cancer Research Fund/American Institute for Cancer Research third Expert report on diet, nutrition, physical activity, and cancer: impact and future directions;Clinton SK;J Nutr,2020
3. From genome-wide association studies to Mendelian randomization: novel opportunities for understanding cardiovascular disease causality, pathogenesis, prevention, and treatment;Benn M;Cardiovasc Res,2018
4. Applying Mendelian randomization to appraise causality in relationships between nutrition and cancer;Wade KH;Cancer Causes Control,2022
5. Systematic review of Mendelian randomization studies on risk of cancer;Markozannes G;BMC Med,2022