The relationship between vegetable/fruit consumption and gallbladder/bile duct cancer: A population-based cohort study in Japan

Int J Cancer. 2017 Mar 1;140(5):1009-1019. doi: 10.1002/ijc.30492. Epub 2016 Nov 29.


Vegetable and fruit consumption may have a protective effect against several types of cancers. However, the effect on biliary cancers is unclear. We investigated the association of vegetable/fruit consumption with the risks of gallbladder cancer (GBC), intrahepatic bile duct cancer (IHBDC) and extrahepatic bile duct cancer (EHBDC) in a population-based prospective cohort study in Japan. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using the Cox proportional hazard model, and the exposure level was categorized into quartiles, with the lowest group used as the reference. A total of 80,371 people aged 45 to 74 years were enrolled between 1995 and 1999, and followed up for 1,158,632 person-years until 2012, during which 133 GBC, 99 IHBDC, and 161 EHBDC cases were identified. Increased consumption of total vegetable and fruit was significantly associated with a decreased risk of EHBDC (HR = 0.49; 95% CI: 0.29-0.81 for the highest group; p trend = 0.005). From the analysis of relevant nutrients, significantly decreased risk of EHBDC was associated with folate and insoluble fiber (HR = 0.48, 0.53; 95% CI: 0.28-0.85, 0.31-0.88 for the highest group; p trend = 0.010, 0.023; respectively), and a significant trend of decreased EHBDC risk associated with vitamin C was observed (p trend = 0.029). No decreased risk of GBC and IHBDC was found. Our findings suggest that increased vegetable/fruit consumption may decrease a risk of EHBDC, and folate, vitamin C, and insoluble fiber might be key contributors to the observed protective effect.

Keywords: JPHC; Japanese; extrahepatic bile duct cancer; fruit; gallbladder cancer; intrahepatic bile duct cancer; prospective study; vegetable.

MeSH terms

  • Adult
  • Alcohol Drinking / epidemiology
  • Ascorbic Acid
  • Bile Duct Neoplasms / epidemiology*
  • Bile Duct Neoplasms / prevention & control
  • Carcinoma / epidemiology*
  • Carcinoma / prevention & control
  • Cholelithiasis / epidemiology
  • Comorbidity
  • Diabetes Mellitus / epidemiology
  • Diet*
  • Dietary Fiber
  • Female
  • Folic Acid
  • Follow-Up Studies
  • Fruit*
  • Gallbladder Neoplasms / epidemiology*
  • Gallbladder Neoplasms / prevention & control
  • Hepatitis, Viral, Human / epidemiology
  • Humans
  • Japan / epidemiology
  • Life Style
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Prospective Studies
  • Smoking / epidemiology
  • Surveys and Questionnaires
  • Vegetables*


  • Dietary Fiber
  • Folic Acid
  • Ascorbic Acid