Former smokers have a higher risk of small cell lung cancer (SCLC), which, in some cases, is partially mediated by chronic obstructive pulmonary disease (COPD), according to a large, multinational study.

Compared to non-smokers, former and current smokers had a significantly higher risk of SCLC (odds ratio [OR], 6.21, 95 percent CI, 5.21-7.41 and OR, 26.72, 95 percent CI, 22.54-31.68, respectively; p<0.001).

Smokers who have COPD had a 1.86 times higher risk of SCLC (95 percent CI, 1.61-2.16; p<0.001) than smokers without COPD. Among former smokers, COPD indirectly mediated the risk of SCLC (OR, 1.03; p<0.001), though this only occurred in less than 10 percent of cases. [EBioMedicine 2015;doi:10.1016/j.ebiom.2015.09.031]

A longer period of cessation greatly reduced the risk of SCLC in a dose-response manner (OR, 0.57, 95 percent CI, 0.45-0.73 for individuals who had quit for 5-9 years versus OR, 0.11, 95 percent CI, 0.09-0.14; p<0.001 for those who had quit for more than 20 years).

Previous studies have shown that even after years of cessation, the risk of SCLC remains higher than that of non-smokers, which has been attributed to irreversible lung damage. [Resp Res 2013;14:97]

The association between COPD and overall lung cancer is well-established, and newer studies have demonstrated the link between cigarette smoking and concurrent COPD and NSCLC. [Ann Intern Med 1987;106:512-518; Int J Cancer 2014;134:961-970]

To investigate the impact of smoking and the specific role of COPD on SCLC risk, researchers analyzed data from 24 studies from the International Lung Cancer Consortium (ILCCO) that included 4,346 patients with SCLC and 37,942 without the disease.

According to the researchers, SCLC has a high mortality and relapse rate, which raises the need for preventive measures. This is the largest study investigating the link between multiple smoking risk factors, COPD and SCLC risk, as well as the first to look into COPD as a mediator between smoking and SCLC.

Study limitations include potential underdiagnosis of COPD leading to overestimation of smoking patterns. The use of corticosteroids or statins which improve COPD and reduce lung cancer risk may also have distorted the results. Researchers called for further investigation into the role of genetics and the pathways by which COPD, smoking and lung cancer are connected in order to enable early diagnosis of SCLC.