Risk rose in tandem with dose and duration of proton pump inhibitor (PPI)
October 31, 2017
long-term use of proton pump inhibitors (PPIs), a class of drugs commonly used
to treat acid reflux, is linked to a more than doubling in the risk of
developing stomach cancer, finds research.
The long term use of
proton pump inhibitors (PPIs), a class of drugs commonly used to treat acid
reflux, is linked to a more than doubling in the risk of developing stomach
cancer, finds research published online in the journal Gut.
The risk rose in tandem
with the dose and duration of treatment following elimination of Helicobacter
pylori, the bacteria implicated in the development of stomach cancer, the
Eliminating H pylori
from the gut significantly lowers a person’s risk of developing stomach cancer.
But a substantial proportion of those in whom treatment is successful still go
on to develop the disease, the third leading cause of cancer death in the
research has found an association between PPI use and heightened stomach cancer
risk, but it was unable to factor in the potential role of H pylori
itself, so undermining the strength of the findings.
To try and get round
this, the researchers compared the use of PPIs with another type of drug used
to dampen down acid production called histamine H2 receptor antagonists (H2
blockers) in 63,397 adults treated with triple therapy — a combination of a
PPI and two antibiotics to kill off H pylori over 7 days — between 2003
They were subsequently
monitored until they either developed stomach cancer, died, or the study ended
(end of December 2015), whichever came first. The average monitoring period
lasted 7.5 years.
During this time, 3271
(5%) people took PPIs for an average of nearly three years; and 21,729 took H2
In all, 153 (0.24%)
people developed stomach cancer after triple therapy. None tested positive for H
pylori at the time, but all had long standing gastritis (inflammation of
the stomach lining).
Taking PPIs was
associated with a more than doubling (2.44) in the risk of developing stomach
cancer, while taking H2 blockers was not associated with any such heightened
The average time between
triple therapy and the development of stomach cancer was just under 5 years.
More frequent use was
associated with greater risk, with daily use linked to a more than quadrupling
in risk (4.55) compared with weekly use.
And the longer PPIs were
used, the greater was the risk of developing stomach cancer, rising to 5-fold
after more than a year, to more than 6-fold after two or more years, and to
more than 8-fold after three or more years.
This is an observational
study, so no firm conclusions can be drawn about cause and effect, and PPIs are
generally considered safe, say the researchers.
But recent research has
linked their long term use to various unwanted effects, including pneumonia,
heart attack, and bone fracture, they point out, adding that PPIs are known to
stimulate the production of gastrin, a powerful growth factor.
dose-response and time response trend” in the use of PPIs and stomach
cancer risk, prompt them to suggest that doctors “should exercise caution
when prescribing long-term PPIs…even after successful eradication of H
1. Ka Shing Cheung, Esther W
Chan, Angel Y S Wong, Lijia Chen, Ian C K Wong, Wai Keung Leung. Long-term
proton pump inhibitors and risk of gastric cancer development after treatment
forHelicobacter pylori: a population-based study. Gut, 2017;
gutjnl-2017-314605 DOI: 10.1136/gutjnl-2017-314605