Yunyang Deng1, Junjie Huang1, Martin Chi Sang Wong2,3,4. 1. The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, 999077, China. 2. The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, 999077, China. wong_martin@cuhk.edu.hk. 3. School of Public Health, The Chinese Academy of Medical Sciences and the Peking Union Medical College, Beijing, 100000, China. wong_martin@cuhk.edu.hk. 4. School of Public Health, Peking University, Beijing, 100000, China. wong_martin@cuhk.edu.hk.
Abstract
PURPOSE: Previous observational studies have shown that alcohol and coffee were associated with colorectal cancer (CRC) risk, but the causal relationships have not been adequately explored. This study aimed to assess the potential causal associations of alcohol and coffee with CRC risk using Mendelian randomization (MR) analyses in an East Asian population. METHODS: Publicly available summary-level genome-wide association studies data on ever/never alcohol drinker (n = 165,084), alcohol consumption (n = 58,610), coffee consumption (n = 152,634), and CRC (7062 cases and 195,745 controls) were obtained from the BioBank Japan (BBJ). Single-nucleotide polymorphisms (SNPs) that were significantly related to the exposures were identified as instrumental variables. Five, two, and six SNPs were used for ever/never alcohol drinkers, alcohol consumption, and coffee consumption, respectively. The inverse variance weighted method was used as the main MR method to calculate the odds ratios (ORs) and 95% confidence intervals (95% CIs) of CRC risk per one-unit change in exposures. RESULTS: Genetically predicted ever/never alcohol drinkers (OR: 1.08; 95% CI 1.06, 1.11; P < 0.001) and alcohol consumption (OR: 1.39; 95% CI 1.21, 1.60; P < 0.001) were positively associated with CRC risk. Conversely, genetically predicted coffee consumption was inversely related to CRC risk, with an OR (95% CI) of 0.80 (0.64, 0.99) (P = 0.037). CONCLUSION: Genetically predicted alcohol use and consumption were risk factors for CRC while genetically predicted coffee consumption was a protective factor. Our findings highlight the effectiveness of keeping healthy dietary habits to prevent CRC. Further studies with more valid SNPs and CRC cases are needed. Validation of our findings is also recommended.
PURPOSE: Previous observational studies have shown that alcohol and coffee were associated with colorectal cancer (CRC) risk, but the causal relationships have not been adequately explored. This study aimed to assess the potential causal associations of alcohol and coffee with CRC risk using Mendelian randomization (MR) analyses in an East Asian population. METHODS: Publicly available summary-level genome-wide association studies data on ever/never alcohol drinker (n = 165,084), alcohol consumption (n = 58,610), coffee consumption (n = 152,634), and CRC (7062 cases and 195,745 controls) were obtained from the BioBank Japan (BBJ). Single-nucleotide polymorphisms (SNPs) that were significantly related to the exposures were identified as instrumental variables. Five, two, and six SNPs were used for ever/never alcohol drinkers, alcohol consumption, and coffee consumption, respectively. The inverse variance weighted method was used as the main MR method to calculate the odds ratios (ORs) and 95% confidence intervals (95% CIs) of CRC risk per one-unit change in exposures. RESULTS: Genetically predicted ever/never alcohol drinkers (OR: 1.08; 95% CI 1.06, 1.11; P < 0.001) and alcohol consumption (OR: 1.39; 95% CI 1.21, 1.60; P < 0.001) were positively associated with CRC risk. Conversely, genetically predicted coffee consumption was inversely related to CRC risk, with an OR (95% CI) of 0.80 (0.64, 0.99) (P = 0.037). CONCLUSION: Genetically predicted alcohol use and consumption were risk factors for CRC while genetically predicted coffee consumption was a protective factor. Our findings highlight the effectiveness of keeping healthy dietary habits to prevent CRC. Further studies with more valid SNPs and CRC cases are needed. Validation of our findings is also recommended.
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