Associations between first and second primary cancers: a population-based study.

BACKGROUND: Patients surviving certain types of cancer are at increased risk of a second primary cancer. We tested the hypothesis that excess risk of a second primary cancer is due mainly to excess risk of it being the same type of cancer as the first, rather than to excess risk of it being a different type.
METHODS: We conducted a nationwide study using data from three dabatases for the entire Danish population (n = 7,493,705) from 1980 through 2007. For each type of cancer, we performed a nested study matching each patient with incident cancer diagnosed in that period with up to five controls who did not have the examined cancer at the time of diagnosis. We used Cox regression models to calculate individual risk estimates and meta-analysis techniques to calculate aggregated risk estimates.
RESULTS: A total of 765,255 people had one or more diagnoses of primary cancer (total 843,118 diagnoses) during the study period. The aggregated hazard ratio (HR) for risk of any second primary cancer after any first cancer was 1.25 (95% confidence interval [CI] 1.24-1.26), with heterogeneity among cancer types. The aggregated HR for risk of a second primary cancer of the same type as the first was 2.16 (95% CI 1.98-2.34). The aggregated HR for risk of a second cancer of a different type from the first was 1.13 (95% CI 1.12-1.15). Results were similar when we excluded second primary cancers occurring within 1, 2, 5 or 10 years after the first cancer. Overall, we observed 74 significant associations among 27 types of first cancer and 27 possible types of second primary cancer.
INTERPRETATION: Excess risk of a second primary cancer was due mainly to a 2.2-fold risk of the second cancer being the same type as the first, whereas the risk of it being a different type was only 1.1-fold. However, heterogeneity among cancer types was substantial.