Gallstones and incident colorectal cancer in a large pan-European cohort study

Heather A. Ward, Neil Murphy, Elisabete Weiderpass, Michael F. Leitzmann, Elom Aglago, Marc J. Gunter, Heinz Freisling, Mazda Jenab, Marie Christine Boutron-Ruault, Gianluca Severi, Franck Carbonnel, Tilman Kühn, Rudolf Kaaks, Heiner Boeing, Anne Tjønneland, Anja Olsen, Kim Overvad, Susana Merino, Raul Zamora-Ros, Miguel Rodríguez-BarrancoMiren Dorronsoro, Maria Dolores Chirlaque, Aurelio Barricarte, Aurora Perez-Cornago, Antonia Trichopoulou, Christina Bamia, Pagona Lagiou, Giovanna Masala, Sara Grioni, Rosario Tumino, Carlotta Sacerdote, Amalia Mattiello, Bas Bueno-de-Mesquita, Roel Vermeulen, Carla Van Gils, Hanna Nyström, Martin Rutegård, Dagfinn Aune, Elio Riboli, Amanda J. Cross

Research output: Contribution to journalArticlepeer-review


Gallstones, a common gastrointestinal condition, can lead to several digestive complications and can result in inflammation. Risk factors for gallstones include obesity, diabetes, smoking and physical inactivity, all of which are known risk factors for colorectal cancer (CRC), as is inflammation. However, it is unclear whether gallstones are a risk factor for CRC. We examined the association between history of gallstones and CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a prospective cohort of over half a million participants from ten European countries. History of gallstones was assessed at baseline using a self-reported questionnaire. The analytic cohort included 334,986 participants; a history of gallstones was reported by 3,917 men and 19,836 women, and incident CRC was diagnosed among 1,832 men and 2,178 women (mean follow-up: 13.6 years). Hazard ratios (HR) and 95% confidence intervals (CI) for the association between gallstones and CRC were estimated using Cox proportional hazards regression models, stratified by sex, study centre and age at recruitment. The models were adjusted for body mass index, diabetes, alcohol intake and physical activity. A positive, marginally significant association was detected between gallstones and CRC among women in multivariable analyses (HR = 1.14, 95%CI 0.99–1.31, p = 0.077). The relationship between gallstones and CRC among men was inverse but not significant (HR = 0.81, 95%CI 0.63–1.04, p = 0.10). Additional adjustment for details of reproductive history or waist circumference yielded minimal changes to the observed associations. Further research is required to confirm the nature of the association between gallstones and CRC by sex.

Original languageEnglish
Pages (from-to)1510-1516
Number of pages7
JournalInternational Journal of Cancer
Issue number6
Publication statusPublished - Sep 15 2019


  • cohort
  • colorectal cancer
  • EPIC
  • Gallstones

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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