Association between atherosclerosis and female lung cancer: a Danish cohort study

Patients suffering from atherosclerotic diseases are prone to repeated episodes of ischemia/reperfusion that has been demonstrated to induce oxidative stress by formation of oxygen free radicals. It might therefore be expected that such endogenously exposure to free radicals increases the individual cancer risk in patients with atherosclerotic diseases. We therefore studied the sex-specific risk of lung cancer and other cancers in atherosclerotic patients in a prospective study conducted in the Copenhagen area. The study cohort was linked to the Danish Hospital Discharge Register and we identified 2261 1-year survivors of atherosclerotic diseases through 1977 and 1993, while 26150 of the study subjects had no record of an atherosclerotic diagnosis. After linkage to the Danish Cancer Registry associations between atherosclerosis and cancer were analysed for each sex separately by means of Cox proportional hazard regression models. Atherosclerotic women had a significant RR of lung cancer of 3.26 (95% CI: 1.95-5.46) compared to non-atherosclerotic women after adjustment for age, calendar period, study population, smoking habits, school education and alcohol consumption. No significant risk of male lung cancer, RR=1.12 (95% CI: 0.77-1.64), or other smoking-related cancers in either sex was observed after multivariate adjustment. Atherosclerosis did not predict non-smoking-related cancers in general in either men, RR=0.91 (95% CI 0.69-1.20), or women, RR=0.93 (95% CI: 0.64-1.35). We hypothesize that oxidative stress due to episodes of ischemia/reperfusion increases the risk of lung cancer in atherosclerotic females because of a gender specific susceptibility to oxidative DNA damage.