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

T. J. Ballinger, Z. Djuric, S. Sardesai, K. Hovey, C. Andrews, T. M. Braskey, T. E. Rohan, N. Saquib, A. H. Shadyab, M. Simon, J. Wactawski-Wende, R. Wallace, I. Kato

Research output: Contribution to journalArticlepeer-review

Abstract

PURPOSE: Proton pump inhibitors (PPIs) inhibit fatty acid synthase (FAS), a critical enzyme in lipogenesis, energy balance, and cancer cell survival. We aimed to evaluate the association of PPI use with incidence of common obesity- related cancers in women: postmenopausal breast, colorectal, and endometrial cancers. METHODS: Our study included 124,931 postmenopausal who were enrolled in the Women's Health Initiative (WHI) observational study and clinical trials, and had responded to a year 3 follow-up assessment. We examined prescription and over the counter use of PPI and/or histamine 2 receptor antagonists (H2RA) at baseline and year 3, to isolate potential effects of FAS inhibition by PPI rather than simply acid suppression. Incident cancer cases were physician-adjudicated. Cox proportional hazard regression models were used to estimate multivariable hazard ratios (HR) and 95% confidence intervals (CI) for associations between PPI and/or H2RA use and cancer incidence after year 3. RESULTS: There were 7956 PPI ever users (with or without H2RA use) and 9398 H2RA only users. PPI or H2RA use was not associated with risk of breast cancer (n=9186 cases), compared to women who did not use either agent (HR 1.01, 95% CI 0.93-1.10 and HR 0.95 95% CI 0.87-1.03, respectively). The incidence of colorectal cancer (n=2280) was significantly lower in PPI users (HR 0.75, 95% CI 0.61-0.92), but not in H2RA users (HR 1.13, 95% CI 0.97-1.31). This association was strengthened with increasing duration (p=0.006) and potency (p=0.005) of PPI use and held regardless of BMI or NSAID use. PPI or H2RA use was not associated with endometrial cancer (n=1231) (HR 0.81, 95% CI 0.61-1.07 and HR 1.13, 95% CI 0.91-1.40, respectively), but showed a trend in decreased risk with increasing PPI potency (P=0.048). CONCLUSIONS: Among postmenopausal women, PPI use, but not H2RA use, demonstrated an inverse, dose-responsive association with colorectal cancer incidence. This was consistent with preclinical data that FAS inhibition prevents colon cancer progression and supports further investigation of this commonly used medication as a cancer preventive agent. PPI use was not associated with incidence of breast or endometrial cancer.

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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