Statins may help prevent lung cancer,
at least in men, according to research published in
the May issue of the journal Chest. The finding
comes from a study involving nearly half a million US
veterans that suggests that taking statins for more
than six months can reduce lung cancer risk by 55%.
Longer periods can achieve even greater risk reduction.
But don't expect regulators to approve statins for smokers
anytime soon. There are still plenty of caveats.
UNAMBIGUOUS
EFFECTS
The research was led by doctors from two Louisana sites.
They looked at the records of more than 480,000 veterans,
98% of whom were male, from the south-eastern US.
Of these, 163,662 (33.8%) were
taking statins, and 7,280 (1.5%) had lung cancer. Among
those who had lung cancer, 27.4% were taking statins.
Among those who did not have the disease, 33.9% were
taking statins.
After adjustment for age, race,
BMI, smoking, alcohol use and diabetes, the researchers
found that statins conferred a relative risk for lung
cancer of 0.45 in subjects who had taken them for more
than six months. The protective effect seemed to increase
over time, with a relative risk of just 0.23 in those
subjects who had been taking statins for over four years.
Among smokers and former smokers,
statin use for at least six months conferred a lung
cancer risk reduction of 43%; among never-smokers, the
risk reduction was 58%.
Strangely, there appeared to be
a sharp rise in lung cancer risk in the first six months
of taking a statin, with an odds ratio of 2.59 during
that period. The authors are convinced, however, that
this is an artifact of the patients' enrolment —
cancers being detected and statins prescribed when they
entered the VA system.
USING
HISTORY LESSONS
Nevertheless, this early spike will have to be revisited.
Beta-carotene was once identified as a potential lung
cancer prophylactic, based on in vitro and epidemiological
evidence, but when prospective trials put it to test,
it was found to increase rates of the disease.
Statins have already shown evidence
of a cancer prevention effect in epidemiological studies.
A 2004 meta-analysis in the Journal of Clinical Oncology
and a 2005 study in the International Journal of
Cancer both found a protective effect, albeit a
milder one than was measured in this study.
The former study found a risk reduction
for all cancers of 20% in statin users overall, and
36% in those who had taken statins for more than four
years. The latter study found statin users' risk of
developing any cancer was 86% that of non-users, and
73% that of users of other lipid therapies.
There are several plausible biological
mechanisms by which statins could resist cancer. They
increase apoptosis, programmed cell death; they suppress
angiogenesis through their effects on vascular endothelial
growth factor; and they reduce cancer cells' potential
for invasion and metastasis by interacting with adhesion
molecules.
Unfortunately, there are also plausible
mechanisms that could knock this study's findings off
course.
A potential limitation is that
statins are typically prescribed along with advice to
get more exercise and eat a better diet. If either of
these lifestyle changes reduced lung cancer risk —
and eating a better diet almost certainly does —
then their benefits confound observed drug effects.
HONEST
SCIENCE
A strength of the study is that the authors took no
money from any statin manufacturer. In fact no attempt
was made to distinguish between different types of statin
or different doses in the analysis. That's perhaps a
blessing in disguise, because it's too soon to start
making actual clinical judgements based on this data,
by the researchers' own admission.
"Well-designed randomized prospective
double-blinded placebo controlled clinical trials are
necessary to validate the value of statins in lung cancer
prevention and treatment," they conclude.
Three specialists from the H Lee
Moffitt Cancer Center, writing in an accompanying commentary,
agree that this is a signpost to future research, not
a call to change practice, at least not yet. Prospective
data need to be obtained in controlled clinical trials,
they argue. Until data from randomized controlled phase
III trials become available, both researchers and commentators
agree that statins should be given purely for lipid
treatment.
But the study has been widely reported,
and patients may not be feeling so patient. Don't be
surprised if one or two smoking patients develop a sudden
interest in their lipid levels.
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