Risk of second cancer after chronic lymphocytic leukemia

Smoking is not considered a risk factor for chronic lymphocytic leukemia (CLL) yet increased lung cancer risk has been reported for these patients. Little data exist on the temporal variation in lung cancer risk after CLL, or its histological composition. We investigated the occurrence of second cancers in a large cohort of CLL patients with particular emphasis on lung cancer and its major subtypes. We followed all patients diagnosed with CLL in Denmark in the period 1943-2003 (n = 12,373) for the occurrence of second cancers. The relative risk was expressed as the standardized incidence ratio (SIR), i.e. the ratio of observed to expected number of cancers, based on incidence rates for the Danish population. During follow-up 1,105 cancers occurred among the CLL patients (SIR = 1.59 (95% CI 1.50-1.69)). SIR for all cancers combined remained elevated more than 10 years after CLL (SIR = 1.80 (1.56-2.08)). Lung cancer occurred in 141 patients (SIR = 1.61 (1.37-1.90)). The relative risk of lung cancer did not vary by gender, or time of follow-up, but was higher in younger (SIR(<60 years) = 2.22 (1.62-3.06)) than in older (SIR(70-79 years) = 1.21 (0.88-1.68)) age-groups. Elevated risks were observed for adenocarcinoma (SIR = 2.20 (1.57-3.08)) and squamous cell carcinoma (SIR = 1.52 (1.06-2.17)) of the lung. We speculate that shared genetic risk factors may explain the accumulation of lung and other cancers in CLL patients.