Journal article
Proton Pump Inhibitor Use and Obesity-Associated Cancer in the Women's Health Initiative
Nutrition and cancer, Vol.75(1), pp.265-275
2023
DOI: 10.1080/01635581.2022.2108467
PMCID: PMC9772040
PMID: 35968582
Abstract
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 (
= 9186) nor risk of endometrial cancer (
= 1231). The risk of CRC (
= 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). The association of PPI use with CRC was apparent regardless of BMI or NSAID use, and was stronger with longer PPI duration (
= 0.006) and potency (
= 0.005). The findings that PPI use, but not H2RA use, demonstrate an inverse dose-response relationship with risk of CRC is consistent with preclinical data showing FASN inhibition prevents colon cancer progression and supports a role of PPI in CRC prevention.
Details
- Title: Subtitle
- Proton Pump Inhibitor Use and Obesity-Associated Cancer in the Women's Health Initiative
- Creators
- Tarah J Ballinger - Indiana UniversityZora Djuric - University of MichiganSagar Sardesai - The Ohio State UniversityKathleen M Hovey - State University of New YorkChris A Andrews - State University of New YorkTheodore M Brasky - The Ohio State UniversityJian Ting Zhang - University of ToledoThomas E Rohan - Albert Einstein College of MedicineNazmus Saquib - Sulaiman Al Rajhi CollegesAladdin H Shadyab - Human LongevityMichael Simon - The Barbara Ann Karmanos Cancer InstituteJean Wactawski-Wende - University of ToledoRobert Wallace - University of IowaIkuko Kato - The Barbara Ann Karmanos Cancer Institute
- Resource Type
- Journal article
- Publication Details
- Nutrition and cancer, Vol.75(1), pp.265-275
- DOI
- 10.1080/01635581.2022.2108467
- PMID
- 35968582
- PMCID
- PMC9772040
- NLM abbreviation
- Nutr Cancer
- ISSN
- 0163-5581
- eISSN
- 1532-7914
- Grant note
- N01WH32111 / WHI NIH HHS P30 CA082709 / NCI NIH HHS N01WH42129 / WHI NIH HHS N01WH32122 / WHI NIH HHS N01WH32108 / WHI NIH HHS N01WH32118 / NHLBI NIH HHS N01WH42107 / NHLBI NIH HHS P30 CA046592 / NCI NIH HHS N01WH32119 / WHI NIH HHS N01WH32115 / WHI NIH HHS N01WH32100 / WHI NIH HHS N01WH24152 / WHI NIH HHS N01WH32105 / NHLBI NIH HHS N01WH44221 / WHI NIH HHS N01WH22110 / WHI NIH HHS P30 CA022453 / NCI NIH HHS N01 WH32115 / WHI NIH HHS
- Language
- English
- Date published
- 2023
- Academic Unit
- Epidemiology; Injury Prevention Research Center; Internal Medicine
- Record Identifier
- 9984363644302771
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