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. 2022 Oct;41(10):2113-2123.
doi: 10.1016/j.clnu.2022.08.019. Epub 2022 Aug 25.

Coffee consumption and cancer risk: a Mendelian randomisation study

Paul Carter  1 , Shuai Yuan  2 , Siddhartha Kar  3 , Mathew Vithayathil  4 , Amy M Mason  5 , Stephen Burgess  6 , Susanna C Larsson  7
Affiliations

Coffee consumption and cancer risk: a Mendelian randomisation study

Paul Carter et al. Clin Nutr. 2022 Oct.

Abstract

Background: Coffee contains many bioactive chemicals and associations with cancer have been reported in observational studies. In this Mendelian randomisation (MR) study we investigated the causal associations of coffee consumption with a broad range of cancers.

Materials and methods: Twelve independent genetic variants proxied coffee consumption. Genetically-predicted risk of any cancer (59,647 cases) and 22 site-specific cancers was estimated in European-descent individuals in UK Biobank. Univariable and multivariable MR analyses were conducted.

Results: Genetically-predicted coffee consumption was not associated with risk of any cancer in the main analysis (OR 1.05, 95% CI 0.98-1.14, p = 0.183) but was associated with an increased risk of digestive system cancer (OR 1.28, 95% CI 1.09-1.51, p = 0.003), driven by a strong association with oesophageal cancer (OR 2.79, 95% CI 1.73-4.50, p = 2.5×10-5). This association was consistent after adjustment for genetically-predicted body mass index, smoking and alcohol consumption. There was no strong evidence supporting a causal relationship between genetically-predicted coffee consumption and the majority of cancers studied. However, genetically-predicted coffee consumption was associated with increased risk of multiple myeloma (OR 2.25, 95% CI 1.30-3.89, p = 0.004) and reduced ovarian cancer risk (OR 0.63, 95% CI 0.43-0.93, p = 0.020).

Conclusions: This MR study provides strong support for a causal association of coffee consumption with oesophageal cancer, but not for the majority of cancer types, and the underlying mechanisms require investigation.

Keywords: Cancer; Coffee; Mendelian randomization.

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Conflict of interest statement

Conflict of Interest The authors have no conflicts of interest.

Figures

Fig 1
Fig 1. Associations of genetic predisposition to coffee consumption with site-specific cancers.
Odds ratios are per 50% increase in coffee consumption. Results are obtained from the inverse-variance weighted median method with random-effects model. The I2 statistic quantifies the amount of heterogeneity among estimates based on individual SNPs. UKBB, UK Biobank; CI, confidence interval; OR, odds ratio.
Fig 2
Fig 2. Associations of genetic predisposition to coffee consumption with site-specific cancers with adjustment for BMI.
Odds ratios are per 50% increase in coffee consumption after adjustment for genetically predicted BMI. Results are obtained from the inverse-variance weighted median method with random-effects model. BMI, Body Mass Index; UKBB, UK Biobank; CI, confidence interval; OR, odds ratio.
Fig 3
Fig 3. Associations of genetic predisposition to coffee consumption with site-specific cancers with adjustment for smoking initiation.
Odds ratios are per 50% increase in coffee consumption after adjustment for genetic predisposition to smoking initiation. Results are obtained from the inverse-variance weighted median method with random-effects model. based on individual SNPs. UKBB, UK Biobank; CI, confidence interval; OR, odds ratio.
Fig 4
Fig 4. Associations of genetic predisposition to coffee consumption with site-specific cancers with adjustment for both BMI and smoking initiation.
Odds ratios are per 50% increase in coffee consumption after adjustment for genetic predisposition to BMI and smoking initiation. Results are obtained from the inverse-variance weighted median method with random-effects model. UKBB, UK Biobank; CI, confidence interval; OR, odds ratio.
Fig 5
Fig 5. Associations of genetic predisposition to coffee consumption with site-specific cancers with adjustment for alcohol consumption.
Odds ratios are per 50% increase in coffee consumption after adjustment for genetic predisposition to alcohol consumption. Results are obtained from the inverse-variance weighted median method with random-effects model.. UKBB, UK Biobank; CI, confidence interval; OR, odds ratio.
Fig 6
Fig 6. Associations of genetic predisposition to caffeine consumption with site-specific cancers.
Odds ratios are per 50% increase in caffeine consumption. Results are obtained from the inverse-variance weighted median method with fixed-effects model. UKBB, UK Biobank; CI, confidence interval; OR, odds ratio.
Fig 7
Fig 7. Scatter plots for Mendelian randomization analysis of coffee consumption and risk of oesophageal cancer
(A) associations in UK BioBank (B) associations in FinnGen. Horizontal axis: SNPs’ association with coffee consumption. Vertical axis: SNPs’ association with oeseophageal cancer.
See this image and copyright information in PMC

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