RE: Familial Cancer Clustering of Urothelial Cancer: A Population-Based Case–Control Study

Martin and coworkers reported data on familial associations of urothelial cancers (n = 7266) with urothelial cancers and with other (discordant) cancers based on the Utah Population Database, asserting novelty in being able to control for smoking and histology (1). Studies with multiple discordant cancers are subject to chance findings, but the authors guarded against these by assessing consistency of the findings between first-degree relatives, second-degree relatives, and cousins. They referred to four previous studies on the same subject but stated that their study had the advantages of focusing on urothelial histology and being conducted on a population with a low frequency of smokers, thus reducing confounding by smoking. The concern about smoking is valid, but one of the previous studies was conducted on the same Utah population (2); the remaining three were done in Sweden, which has historically had the lowest frequency of smokers in Europe, particularly for men (15% since 2000; http://www.pnlee.co.uk/downloads/iss/iss-sweden_111024.pdf) (3–5). Moreover, Supplementary Table 2 from Martin et al. (available online) showed a weak association of urothelial cancers with smoking-related cancer (hazard ratio [HR] = 1.13, 95% confidence interval [CI] = 1.07 to 1.20, among first-degree relatives) compared with familial urothelial cancers (HR = 1.73, 95% CI = 1.50 to 1.99).

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