Statins Reduce the Risk of Lung Cancer in Humans CHEST 2007; 131:1282–1288 R4 Byunghyuk Yang

INTRODUCTION I Lung cancer as the m/c cause of cancer mortality in the United States and throughout the world American Cancer Society –Lung cancer for approximately 160,000 deaths in the United States during 2005, in comparison with 125,000 deaths from the combined mortality of colorectal, breast, and prostate cancers Worldwide, almost 600,000 deaths due to lung cancer in 1995 Major risk factors –Tobacco smoke –Exposure to asbestos, arsenic, halo ethers, nickel, and polycyclic aromatic hydrocarbons –Genetic factors –Dietary factors –Presences of underlying benign forms of parenchymal lung diseases such as pulmonary fibrosis

INTRODUCTION II No effective chemopreventive agent 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) –Several studies have shown beneficial effects of statins on the incidence of cancers. We conducted this study to determine if statins have a protective effect against lung cancer in a US veteran population.

Data Source The Veterans Health Administration (VHA) is organized into 21 administrative regions called Veterans Integrated Service Networks (VISNs). VISN 16, or the South Central Veterans Affairs (VA) Health Care Network –Eight-state region that includes Florida, Alabama, Mississippi, Louisiana, Arkansas, Missouri, Oklahoma, and Texas –10 medical centers, 33 community-based outpatient clinics, 7 nursing homes, and 2 domiciliaries The Veterans Health Information Systems and Technology Architecture (Vista)

Study Design Retrospective nested case-control cohort study : 483,733 pateints –The case population consisted of the patients with lung cancer. –The patients without lung cancer made up the control population. Between October 1, 1998, and June 1, 2004 The VA administration defines a frequent VA Health Care System user as any person who was seen in a primary care clinic or was hospitalized in the VA Health Care System during the last 2 years. Multivariate analysis using a multiple unconditional logistic regression to determine significant effect of statin use on the risk for lung cancer adjusting for the effects of age, sex, race, body mass index (BMI), smoking, alcohol use, and diabetes The duration of statin defined as the time of usage of statins prior to the diagnosis of lung cancer or the time of usage of the statin until the data collection completion date

REUSTS

1.5 % (1.5 %)

DISCUSSION I To date, there is no effective chemopreventive agent identified for lung cancer. –Beta caroten –Antioxidants vitamins. especially derivatives of vitamins A and E –Green and yellow vegetables, fruits Studies in animal models and from epidemiologic data : preexisting cancer and retrospective nature –Newman and Hulley reviewed animal studies with lipid-lowering therapy and concluded that statins and fibrates might cause cancers in rodents. –Epidemiologic cohort studies in humans also demonstrated that low cholesterol levels were associated with an increase in cancer death. Meta-analysis  no associtation

DISCUSSION II Statin as an anticancer agent –Graaf et al35 conducted a casecontrol study with 3,129 cancer cases and 16,976 control subjects, which showed a 20% reduction in overall cancer risk in statin users. –A nested casecontrol study36 found a 28% lower risk of all cancers in statins users compared with those receiving bile acid binders. –In vitro and cross-sectional studies12,13,38–46 have shown anticancer activity of statins on several kinds of cancers including colon, prostate, lung, hepatocellular carcinoma, breast cancer, astrocytomas, glioblastoma multiform, mesothelioma, leukemia, myeloma, medulloblastoma, and renal cell carcinoma.

DISCUSSION III Our data indicate that statin use 6 months in duration was associated with a significant risk reduction in the incidence of lung cancer across all age groups, race, and BMI. This protective effect was even seen in smokers. Limitations –Population based, an observational retrospective nested case-control cohort study : unknown biases or confounders –Not adjusted for other risk factors –Dose, duration, and type of statin use were not factored into our analysis. Strenths –Computerized database to minimize the exposure misclassification and recall bias

CONCLUSION Statin use 6 months was associated with a 55% reduction in the odds for lung cancer. Our study suggests that statins have a potential role in primary chemoprevention for lung cancer. Well-designed randomized prospective double-blinded placebo controlled clinical trials are necessary to validate the value of statins in lung cancer prevention and treatment.