A Prospective Diet-Wide Association Study for Risk of Colorectal Cancer in EPIC

Nikos Papadimitriou, Emmanouil Bouras, Piet A van den Brandt, David C Muller, Areti Papadopoulou, Alicia K Heath, Elena Critselis, Marc J Gunter, Paolo Vineis, Pietro Ferrari, Elisabete Weiderpass, Heiner Boeing, Nadia Bastide, Melissa A Merritt, David S Lopez, Manuela M Bergmann, Aurora Perez-Cornago, Matthias Schulze, Guri Skeie, Bernard SrourAnne Kirstine Eriksen, Stina Boden, Ingegerd Johansson, Therese Haugdahl Nøst, Marco Lukic, Fulvio Ricceri, Ulrika Ericson, José María Huerta, Christina C Dahm, Claudia Agnoli, Pilar Exezarreta Amiano, Anne Tjønneland, Aurelio Barricarte Gurrea, Bas Bueno-de-Mesquita, Eva Ardanaz, Jonna Berntsson, Maria-Jose Sánchez, Rosario Tumino, Salvatore Panico, Verena Katzke, Paula Jakszyn, Giovanna Masala, Jeroen W G Derksen, J Ramón Quirós, Gianluca Severi, Amanda J Cross, Ellio Riboli, Ioanna Tzoulaki, Konstantinos K Tsilidis*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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BACKGROUND & AIMS: Evidence regarding the association of dietary exposures with colorectal cancer (CRC) risk is not consistent with a few exceptions. Therefore, we conducted a diet-wide association study (DWAS) in the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate the associations between several dietary exposures with CRC risk.

METHODS: The association of 92 food and nutrient intakes with CRC risk was assessed in 386,792 participants, 5069 of whom developed incident CRC. Correction for multiple comparisons was performed using the false discovery rate, and emerging associations were examined in the Netherlands Cohort Study (NLCS). Multiplicative gene-nutrient interactions were also tested in EPIC based on known CRC-associated loci.

RESULTS: In EPIC, alcohol, liquor/spirits, wine, beer/cider, soft drinks, and pork were positively associated with CRC, whereas milk, cheese, calcium, phosphorus, magnesium, potassium, riboflavin, vitamin B6, beta carotene, fruit, fiber, nonwhite bread, banana, and total protein intakes were inversely associated. Of these 20 associations, 13 were replicated in the NLCS, for which a meta-analysis was performed, namely alcohol (summary hazard ratio [HR] per 1-SD increment in intake: 1.07; 95% confidence interval [CI], 1.04-1.09), liquor/spirits (HR per 1-SD increment in intake, 1.04; 95% CI, 1.02-1.06), wine (HR per 1-SD increment in intake, 1.04; 95% CI, 1.02-1.07), beer/cider (HR per 1-SD increment in intake, 1.06; 95% CI, 1.04-1.08), milk (HR per 1-SD increment in intake, 0.95; 95% CI, 0.93-0.98), cheese (HR per 1-SD increment in intake, 0.96; 95% CI, 0.94-0.99), calcium (HR per 1-SD increment in intake, 0.93; 95% CI, 0.90-0.95), phosphorus (HR per 1-SD increment in intake, 0.92; 95% CI, 0.90-0.95), magnesium (HR per 1-SD increment in intake, 0.95; 95% CI, 0.92-0.98), potassium (HR per 1-SD increment in intake, 0.96; 95% CI, 0.94-0.99), riboflavin (HR per 1-SD increment in intake, 0.94; 95% CI, 0.92-0.97), beta carotene (HR per 1-SD increment in intake, 0.96; 95% CI, 0.93-0.98), and total protein (HR per 1-SD increment in intake, 0.94; 95% CI, 0.92-0.97). None of the gene-nutrient interactions were significant after adjustment for multiple comparisons.

CONCLUSIONS: Our findings confirm a positive association for alcohol and an inverse association for dairy products and calcium with CRC risk, and also suggest a lower risk at higher dietary intakes of phosphorus, magnesium, potassium, riboflavin, beta carotene, and total protein.

Original languageEnglish
Pages (from-to)864-873.e13
Number of pages23
JournalClinical gastroenterology and hepatology
Issue number4
Early online date24 Apr 2021
Publication statusPublished - Apr 2022

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