Impact of commonly prescribed drugs on the risk of colorectal cancer

Colorectal cancer (CRC) stands as the fourth most prevalent cancer worldwide and the third most common in Sweden. Characterized by a protracted progression stage and insidious onset, CRC poses a considerable challenge for early detection. Most CRCs are typically identified in the middle-to-late stages carrying a poor prognosis without prior screening. Studies revealed that the longterm use of commonly prescribed medications significantly impacts patients’ gut dysbiosis and gastroenterological disorders. The research question addressed in the thesis focuses on investigating the impact of commonly prescribed drugs (e.g., proton pump inhibitors, Helicobacter pylori eradication therapy, menopausal hormone therapies) on the risk of colorectal cancer. To fill the knowledge gap regarding the relationship between these drugs and the risk of CRC, we conducted below four registry-based studies to assess their associations:

In Study I, we included all Swedish adults with ≥180 days of cumulative proton pump inhibitor use between July 2005 and December 2012 from National Prescribed Drug Registry (N = 754,118), excluding individuals with a follow-up of <1 year. With a maximal follow-up of 7.5 years, the exposed population demonstrated a higher colorectal adenocarcinoma risk in maintenance proton pump inhibitor users than in the general population.

In Study II, we selected all patients registered with a diagnosed CRC between 2006 and 2012 (N = 32,411, 54.9% PPI users) and subsequently followed them through registry linkage to the Swedish Causes of Death Registry until December 2013. All-cause and CRC-specific mortalities of proton pump inhibitor users were compared with those who had never received proton pump inhibitor treatment during the same observation period. Overall, proton pump inhibitor use after the CRC diagnosis was associated with increased all-cause and CRC-specific mortality.

In Study III, we extracted 80,381 individuals who received at least one episode of Helicobacter pylori eradication therapy from National Prescribed Drug Registry and compared their relative risks with the general population. We found that Helicobacter pylori eradication therapy did not support a consistent reduction in colorectal adenocarcinoma risk after eradication.

In Study IV, we enrolled all Swedish women who ever received systemic menopausal hormone therapies (N = 290,186) and matched them with those who never had a dispensed prescription of this therapy with a 1:3 ratio during 2005- 2012. We estimated their risks of CRC considering age at treatment initiation, different regimens, and duration after treatment. The results indicated that menopausal hormone therapies might be linked to a decreased colorectal adenocarcinoma risk for both estrogen-only and estrogen-combined progestin regimens.

List of scientific papers

I. Liu Q, Wang X, Engstrand L, Sadr-Azodi O, Fall K, Brusselaers N. Maintenance proton pump inhibitor usage and risk of colorectal cancer: a population-based Swedish cohort study. [Submitted]

II. Wang X, Liu Q, Halfdanarson ÓÖ, Zoega H, Sadr-Azodi O, Engstrand L, Fall K, Brusselaers N. Proton pump inhibitors and survival in patients with colorectal cancer: a Swedish population-based cohort study. British Journal of Cancer. 2021 Sep;125(6):893-900.
https://doi.org/10.1038/s41416-021-01480-0

III. Liu Q, Sadr-Azodi O, Engstrand L, Fall K, Brusselaers N. Helicobacter pylori eradication therapy and the risk of colorectal cancer. [Manuscript]

IV. Liu Q, Simin J, Debelius J, Fall K, Sadr-Azodi O, Engstrand L, Williams C, Brusselaers N. Menopausal hormone therapies and risk of colorectal cancer: a Swedish matched-cohort study. Alimententary Pharmacology & Therapeutics. 2021 Jun;53(11):1216-1225.
https://doi.org/10.1111/apt.16362