Statins reduce the incidence of lung cancer: A study of half a million U.S. veterans.

Reviewer: Christopher Dolinsky, MD
Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 15 de mayo del 2005

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Presenter: V. Khurana
Presenter's Affiliation: VA Medical Center, Shreveport, Louisiana
Type of Session: Scientific

Background

-         Statins (HMG CoA reducatse inhibitors) are a widely studied, effective class of medications used to lower cholesterol in an effort to reduce atherosclerosis and heart disease.
-         In certain animal models, statins have been shown to inhibit tumor growth.
-         The enzyme that statins inhibit (HMG CoA reductaste) has been demonstrated to be increased in tumor cells, and has also been show to be increased before DNA synthesis.
-         A theoretical mechanism for this inhibition is that certain cancer gene proteins require a lipid "tail" to anchor them to tumor cells, and statins may prevent this from occurring.
-         Little data exists on whether or not statins may prevent tumor growth in human beings.

Materials and Methods

-         A retrospective analysis of 484,226 patients from 10 VA medical centers was carried out to determine the effect that statin use has on the subsequent development of lung cancer.
-         The median age was 61.2 years, and 91.7% of the patients were men.
-         Patients were classified as statin users if they had ever been prescribed a statin prior to the diagnosis of lung cancer.
-         Multiple logistic regression analysis was performed, with a 95% confidence interval employed.
-         The primary variables of interest were diagnosis of lung cancer and statin use.
-         Data was adjusted for smoking history, alcohol history, gender and age.

Results

-         Lung cancer was seen in 1.2% of statin users and 1.7% of statin non-users.
-         Statin users had a lower likelihood of developing lung cancer (odds ratio 0.52, p<0.001)
-         When data was controlled for the covariates, they all remained highly significant: smoking OR 1.8 -> p<0.0001, alcohol use OR 1.13 -> p<0.0001,  older age OR 1.038 -> p<0.0001, and female gender OR 0.42 -> p<0.0001.
-         Preliminary subgroup analyses demonstrate that the protective effect of stains increases with duration of statin use.

Author's Conclusions

-         Statins are associated with a 48% decreased risk of developing lung cancer when controlling for certain covariates.
-         This data needs to be evaluated with caution given the study design and limitations of the database.
-         Some factors that are well know to increase lung cancer risk, like asbestos exposure, were not controlled for in this study.
-         A randomized, phase III trial to evaluate the protective effect of stains regarding the development of lung cancer is warranted.

Clinical/Scientific Implications

The authors present an enormous retrospective analysis where an association between statin use and lung cancer development is described.  This large multi-institution database is a powerful tool for retrospective research.  Because this is a retrospective study, it should be viewed as hypothesis generating, not hypothesis proving.  The authors are correct in stating that limitations in the study design preclude definite conclusions about statins as a preventative measure for lung cancer.  This analysis did not examine how the magnitude and duration of cholesterol lowering affected the risk of developing lung cancer.  Also, it did not make mention of the specific statins employed, or how long patients took them.  The analysis would be strengthened with these additional data.  However, this study does raise some very interesting questions.  After further information is collected and analyzed, it may be logical to consider a randomized trial of a statin for lung cancer prevention in high risk patients.



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