Coffee consumption and cancer risk: a Mendelian randomisation study

Paul Carter; Shuai Yuan; Siddhartha Kar; Mathew Vithayathil; Amy M. Mason; Stephen  Burgess; Susanna C.  Larsson

doi:10.1016/j.clnu.2022.08.019

Coffee consumption and cancer risk: a Mendelian randomisation study

Paul Carter
, Shuai Yuan
, Siddhartha Kar
, Mathew Vithayathil
, Amy M. Mason
, Stephen Burgess
, Susanna C. Larsson^*

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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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.

Original language	English
Pages (from-to)	2113-2123
Number of pages	11
Journal	Clinical Nutrition
Volume	41
Issue number	10
DOIs	https://doi.org/10.1016/j.clnu.2022.08.019
Publication status	Published - 24 Aug 2022

Bibliographical note

Funding Information:
This study was supported by a research grant from the Swedish Cancer Society (Cancerfonden). SCL reports grants from the Swedish Cancer Society (Cancerfonden), the Swedish Research Council for Health, Working Life and Welfare (Forte) and the Swedish Research Council (Vetenskapsrådet) during the conduct of the study. PC reports support from a Clinical Research Training Grant from the British Heart Foundation . SK reports support from a Cancer Research UK programme grant, the Integrative Cancer Epidemiology Programme ( C18281/A19169 ) and a Junior Research Fellowship from Homerton College, Cambridge. SB reports support from a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society ( 204623/Z/16/Z ).

Publisher Copyright:
© 2022 The Author(s)

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@article{4ccd69b3be2f42a49db8ca88a2aae622,

title = "Coffee consumption and cancer risk: a Mendelian randomisation study",

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{\textendash}1.14, p = 0.183) but was associated with an increased risk of digestive system cancer (OR 1.28, 95\% CI 1.09{\textendash}1.51, p = 0.003), driven by a strong association with oesophageal cancer (OR 2.79, 95\% CI 1.73{\textendash}4.50, p = 2.5{\texttimes}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{\textendash}3.89, p = 0.004) and reduced ovarian cancer risk (OR 0.63, 95\% CI 0.43{\textendash}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.",

author = "Paul Carter and Shuai Yuan and Siddhartha Kar and Mathew Vithayathil and Mason, \{Amy M.\} and Stephen Burgess and Larsson, \{Susanna C.\}",

note = "Funding Information: This study was supported by a research grant from the Swedish Cancer Society (Cancerfonden). SCL reports grants from the Swedish Cancer Society (Cancerfonden), the Swedish Research Council for Health, Working Life and Welfare (Forte) and the Swedish Research Council (Vetenskapsr{\aa}det) during the conduct of the study. PC reports support from a Clinical Research Training Grant from the British Heart Foundation . SK reports support from a Cancer Research UK programme grant, the Integrative Cancer Epidemiology Programme ( C18281/A19169 ) and a Junior Research Fellowship from Homerton College, Cambridge. SB reports support from a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society ( 204623/Z/16/Z ). Publisher Copyright: {\textcopyright} 2022 The Author(s)",

year = "2022",

month = aug,

day = "24",

doi = "10.1016/j.clnu.2022.08.019",

language = "English",

volume = "41",

pages = "2113--2123",

journal = "Clinical Nutrition",

issn = "0261-5614",

publisher = "Churchill Livingstone",

number = "10",

}

TY - JOUR

T1 - Coffee consumption and cancer risk

T2 - a Mendelian randomisation study

AU - Carter, Paul

AU - Yuan, Shuai

AU - Kar, Siddhartha

AU - Vithayathil, Mathew

AU - Mason, Amy M.

AU - Burgess, Stephen

AU - Larsson, Susanna C.

N1 - Funding Information: This study was supported by a research grant from the Swedish Cancer Society (Cancerfonden). SCL reports grants from the Swedish Cancer Society (Cancerfonden), the Swedish Research Council for Health, Working Life and Welfare (Forte) and the Swedish Research Council (Vetenskapsrådet) during the conduct of the study. PC reports support from a Clinical Research Training Grant from the British Heart Foundation . SK reports support from a Cancer Research UK programme grant, the Integrative Cancer Epidemiology Programme ( C18281/A19169 ) and a Junior Research Fellowship from Homerton College, Cambridge. SB reports support from a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society ( 204623/Z/16/Z ). Publisher Copyright: © 2022 The Author(s)

PY - 2022/8/24

Y1 - 2022/8/24

N2 - 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.

AB - 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.

U2 - 10.1016/j.clnu.2022.08.019

DO - 10.1016/j.clnu.2022.08.019

M3 - Article (Academic Journal)

C2 - 36067583

SN - 0261-5614

VL - 41

SP - 2113

EP - 2123

JO - Clinical Nutrition

JF - Clinical Nutrition

IS - 10

ER -

Coffee consumption and cancer risk: a Mendelian randomisation study

Abstract

Bibliographical note

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