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.
|Original language||English (US)|
|Number of pages||1|
|Journal||Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology|
|State||Published - Jul 1 2022|
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