Basal-Cell Carcinoma of the Skin: A Harbinger of Cutaneous and Noncutaneous Multiple Primary Cancer

Epidemiologic studies of various incidence patterns of multiple primary cancer in patients with cancer have guided research about carcinogenic mechanisms that may apply to several organ sites [1, 2]. At issue is whether risk patterns exist that predict subsequent primary cancer in patients with an index primary cancer of a particular organ and type. Also at issue is whether apparent increases in risk result from 1) shared or common etiologic factors in the pathogenesis of the index and second primary cases of cancer; 2) adverse toxic effects of agents used in the treatment of the index cancer; 3) random or chance effects [for example, those occurring after multiple significance testing]; or 4) spurious associations that are the result of confounding by correlated lifestyle risk factors or by biased ascertainment of new primary cancer as a result of more careful medical surveillance in patients with a history of cancer. The application of criteria for judging the biological plausibility of a common pathogenesis would require mutually excessive occurrences of second primary cancer in patients with cancer and epidemiologic features that are common to the organ sites [2]. The identification of specific and predictive patterns of multiple primary cancer should facilitate the cost-effective targeting of long-term early detection methods or other preventive interventions.

Unlike the population-based cancer registries in the United States, the Danish Cancer Registry has codified the types of nonmelanoma skin cancer since 1978. In patients with squamous-cell skin cancer, Frisch and colleagues [3] reported elevated relative risk for subsequent primary cancer of the buccal cavity, lung, and larynx; cutaneous melanoma; lymphoma; and leukemia. The measure of relative risk was the standardized incidence ratio (SIR) of the actual to expected number of cases of cancer, where the expected number was determined from age-, sex-, and time-specific national cancer incidence …