Statin use may protect smokers against lung cancer

High statin use may reduce the risk of lung cancer in men with hypercholesterolemia, particularly current smokers, according to researchers from Korea who published their results in Clinical Lung Cancer.  

“Several experimental and preclinical studies have suggested that statins have anticancer properties as a result of their inhibition of the mevalonate pathway and impairment of geranylation and farnesylation involved in Ras superfamily signaling,” wrote the authors, led by Yu-Jin Kwon, Department of Family Medicine, Yonsei University College of Medicine, Yong-in Severance Hospital, Yong-in, Republic of Korea.

“Emerging evidence supports the potential roles of statins in the prevention and treatment of cancer; however, a recent meta-analysis and randomized trials failed to show any significant benefit of statins for cancer prevention or treatment. In contrast, results from several observational studies suggest that statin therapy may reduce the risk of lung cancer,” they added.

Thus, the jury is still out on the link between cancer prevention and statins. More recently, researchers of a large meta-analysis published in the World Journal of Meta-Analysis found that statin use decreased the risk of certain cancers, including:

• Colorectal (8%-12%)
• Gastric (27%-44%)
• Hematologic (19%)
• Liver (37%-42%)
• Esophageal (14%-28%)
• Ovarian (21%), and
• Prostate cancer (7%)

Researchers from Scandinavia also conducted a nationwide, retrospective cohort study in 20,559 Swedish women with breast cancer. They found that regular use of statins before breast cancer diagnosis was associated with a lower risk of breast cancer-related mortality compared with non-use or irregular use (HR: 0.77; 95% CI: 0.63-0.95; P=0.014). Further, statin use after breast cancer diagnosis was also associated with a lower risk of breast cancer mortality compared with non-use (HR: 0.83; 95% CI: 075-0.93; P=0.001).

For this most recent study, Kwon et al used data from 16,588 men from Korea’s 2002-2015 National Health Insurance Service–National Health Screening Cohort (NHIS-HEALS). Study participants were aged > 40 years, and had hypercholesterolemia (serum total cholesterol level > 250 mg/dL) or were taking antidyslipidemia drugs at baseline. They were classified as high- or low-statin recipients or non-statin recipients. Using Cox proportional hazards regression, they determined lung cancer risk according to statin receipt.

Participants who received a diagnosis of lung cancer within 1 year of inclusion were excluded to rule out the potential effects of latent cancer. Statins prescribed included pravastatin, simvastatin, atorvastatin, cerivastatin, lovastatin, and fluvastatin. Participants were followed for a median of 12.7 years.

High-statin use was defined as those participants who had a medication possession ratio—a common measure of adherence to medication—above the median of the sample.

From 2005 to 2015, 2.2% (n=363) of participants received a new diagnosis of lung cancer. Compared with those who did not receive statins, those with high-statin receipt had a reduced lung cancer risk (HR: 0.64; 95% CI: 0.47-0.85).

Researchers also did a subgroup analysis according to smoking status, and found that the effects were greatest in current smokers. After adjusting for age, body mass index, systolic blood pressure, glucose, total cholesterol, alcohol intake, physical activity, income, hypertension, and diabetes, the HR for current smokers with high statin use was 0.50 (95% CI: 0.32-0.79), followed by 0.59 (95% CI: 0.27-1.29) in ex-smokers, and 0.83 (95% CI: 0.52-1.31) in non-smokers.

Kwon and colleagues are hopeful about their results, but stressed that more studies are needed to assess the link between—and possible preventive effects of—statin use and lung cancer.

“High statin receipt significantly lowered the lung cancer incidence in Korean men with hypercholesterolemia. The effect was strongest in current smokers. Presently, statins cannot be recommended for the prevention of lung cancer until their effects are demonstrated in well-designed clinical trials,” concluded Kwon and fellow researchers.

This research was supported, in part, by a grant from the Yonsei University College of Medicine.