biostudies-literatureBallinger TJNHLBI NIH HHSNCI NIH HHSNational Institutes of HealthNIHWHI NIH HHS265-275https://www.ebi.ac.uk/biostudies/studies/S-EPMC9772040biostudies-literatureUnknown75(1)Proton pump inhibitors (PPIs) have off-target activity on fatty acid synthase (FASN), a critical enzyme in energy balance and cancer growth. We evaluated risk of common obesity-related cancers: breast, colorectal (CRC), and endometrial, with use of PPI and histamine-2 receptor antagonists (H2RA) in 124,931 postmenopausal women enrolled in the Women's Health Initiative. Incident cancer cases were physician-adjudicated. Cox proportional hazards models were used to estimate multivariable hazard ratios (HR) and 95% confidence intervals (CI) for cancer incidence after year 3. There were 7956 PPI ever users and 9398 H2RA only users. Ever use of either PPI or H2RA was not associated with risk of breast cancer (<i>n</i> = 9186) nor risk of endometrial cancer (<i>n</i> = 1231). The risk of CRC (<i>Nutrition and cancerProton Pump Inhibitor Use and Obesity-Associated Cancer in the Women's Health Initiative.PMC977204032118-32119N01WH32100N01WH32122N01WH4212944221N01WH4210732111-13N01WH32105N01WH32108N01WH442213212224152P30 CA086862P30CA046592P30 CA08270932105-6P30 CA02245332108-9N01WH32111P30 CA046592N01WH32115N01 WH3211542107-26P30CA082709,N01WH32118N01WH32119N01WH2415232100-232115N01WH22110P30CA02245342129-32Simon MWactawski-Wende JSardesai SSaquib NZhang JTRohan TEWallace RKato IDjuric ZHovey KMBrasky TMBallinger TJShadyab AHAndrews CAfalseProton Pump Inhibitor Use and Obesity-Associated Cancer in the Women's Health Initiative.Proton pump inhibitors (PPIs) have off-target activity on fatty acid synthase (FASN), a critical enzyme in energy balance and cancer growth. We evaluated risk of common obesity-related cancers: breast, colorectal (CRC), and endometrial, with use of PPI and histamine-2 receptor antagonists (H2RA) in 124,931 postmenopausal women enrolled in the Women's Health Initiative. Incident cancer cases were physician-adjudicated. Cox proportional hazards models were used to estimate multivariable hazard ratios (HR) and 95% confidence intervals (CI) for cancer incidence after year 3. There were 7956 PPI ever users and 9398 H2RA only users. Ever use of either PPI or H2RA was not associated with risk of breast cancer (<i>n</i> = 9186) nor risk of endometrial cancer (<i>n</i> = 1231). The risk of CRC (<i>2023-01-01T00:00:00Z20232025-04-04T14:13:01.994Z2025-04-04T14:13:01.994ZS-EPMC97720403596858210.1080/01635581.2022.2108467