Are proton pump inhibitors associated with postmenopausal malignancies?

USA: A new study published in Cancer Epidemiology Biomarkers & Prevention suggests that proton pump inhibitors (PPIs) usage did not contribute to increased risk of breast or endometrial cancer and was found to have an inverse, dose-responsive relationship with colorectal cancer risk in postmenopausal women.

Proton pump inhibitors work by inhibiting fatty acid synthase (FAS), an enzyme that is essential for lipogenesis, energy balance, and cancer cell viability. T J Ballinger and colleagues undertook this study to assess the relationship between PPI usage and the risk of three prevalent obesity-related malignancies in women: colorectal, postmenopausal breast, and endometrial cancer.

This study comprised 124,931 postmenopausal women who participated in the Women's Health Initiative (WHI) epidemiological study and clinical trials and completed a year 3 follow-up evaluation. Prescription and over-the-counter usage of PPI and/or histamine 2 receptor antagonists (H2RA) were investigated at baseline and year 3 to identify possible effects of FAS inhibition by PPI rather than just acid suppression. Cases of incident cancer were judged by a physician. Multivariable hazard ratios (HR) and 95 percent confidence intervals (CI) for relationships between PPI and/or H2RA consumption and cancer incidence after year 3 were estimated using Cox proportional hazard regression models.

The key findings of this study were as follows:

1. There were 7956 PPI users who had used it before (with or without H2RA) and 9398 H2RA-only users.

2. When compared to women who did not take either drug, PPI or H2RA usage was not related to an increased risk of breast cancer.

3. Colorectal cancer incidence was considerably reduced in PPI users but not in H2RA users.

4. This relationship was enhanced with increasing PPI duration and potency and remained regardless of BMI or NSAID usage.

5. PPI or H2RA usage was not linked to endometrial cancer, but there was a tendency toward a lower risk as PPI potency increased.

In conclusion, this study data was consistent with preclinical findings showing that inhibiting FAS reduces colon cancer growth, and it justifies future research into this routinely used the medicine as a cancer prevention agent. PPI usage was not linked to an increased risk of breast or endometrial cancer.

Reference:

Ballinger, T., Djuric, Z., Sardesai, S., Hovey, K., Andrews, C., Braskey, T., Rohan, T., Saquib, N., Shadyab, A., Simon, M., Wactawski-Wende, J., Wallace, R., & Kato, I. (2022). Proton Pump Inhibitor Use and Obesity-Associated Cancers in the Women's Health Initiative. In Cancer Epidemiology, Biomarkers & Prevention (Vol. 31, Issue 7, pp. 1511–1511). American Association for Cancer Research (AACR). https://doi.org/10.1158/1055-9965.epi-22-0475