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Proton Pump Inhibitor Use and Obesity-Associated Cancer in the Women's Health Initiative

Tarah J Ballinger1, Zora Djuric2, Sagar Sardesai3

  • 1Department of Medicine, Indiana University School of Medicine, Indianapolis, IN.

Nutrition and Cancer
|August 15, 2022
PubMed

Insights

Proton pump inhibitors (PPIs) may lower colorectal cancer (CRC) risk, unlike H2RAs. This study in postmenopausal women suggests PPIs could play a role in CRC prevention, potentially via FASN inhibition.

Area of Science:

  • Oncology
  • Gastroenterology
  • Pharmacology

Background:

  • Proton pump inhibitors (PPIs) interact with fatty acid synthase (FASN), an enzyme implicated in cancer growth and energy metabolism.
  • Obesity-related cancers, including breast, colorectal (CRC), and endometrial cancers, pose a significant health concern.

Purpose of the Study:

  • To investigate the association between the use of PPIs and histamine-2 receptor antagonists (H2RAs) and the risk of developing common obesity-related cancers.
  • To explore potential differences in cancer risk between PPI and H2RA users, considering FASN inhibition as a possible mechanism.

Main Methods:

  • A cohort of 124,931 postmenopausal women from the Women's Health Initiative was analyzed.
  • Physician-adjudicated incident cancer cases were identified.
  • Cox proportional hazards models were employed to estimate hazard ratios (HR) and 95% confidence intervals (CI) for cancer incidence, adjusting for relevant covariates.

Main Results:

  • PPI use was associated with a significantly lower risk of colorectal cancer (CRC) (HR = 0.75, 95% CI = 0.61-0.92).
  • H2RA use was not associated with a significant change in CRC risk (HR = 1.13, 95% CI = 0.97-1.31).
  • No significant association was found between PPI or H2RA use and the risk of breast or endometrial cancer.

Conclusions:

  • PPI use, but not H2RA use, demonstrated a reduced risk of colorectal cancer, with a dose-response relationship observed.
  • These findings align with preclinical data suggesting FASN inhibition by PPIs may prevent colon cancer progression.
  • The study supports a potential role for PPIs in the prevention of colorectal cancer.

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