This study succeeded in identifying an association between PC and a prior diagnosis of UC. Our finding supported and built upon the earlier study by Pelucchi et al 
, which found that the risk for PC was increased for those reporting urinary tract stones. Furthermore, after analyzing by stone location, we found that PC was associated with kidney calculus (OR
1.71), bladder calculus (OR
2.06), unspecified calculus (OR
1.66), and ≥2 locations of UC (OR
1.73). However, the association between PC and prior ureter calculus was not statistically significant.
UC has two etiological characterizations, the primary being metabolic and the secondary including anatomic, infectious, medication related, and disease related causes. Previous studies have established the association between UC and metabolic syndrome (MS), which is characterized by a cluster of features including dyslipidemia, hyperglycemia, hypertension, obesity, and insulin resistance 
. Such symptoms have been demonstrated in a rat model of metabolic syndrome to precipitate changes in urinary constituents and to lead to an increased risk of uric acid and calcium stone formation 
. One prospective longitudinal study in humans has demonstrated that uric acid stone formers have a significantly higher prevalence of diabetes and glucose intolerance, and an elevated serum triglyceride concentration compared to normal controls 
. As the metabolic derangements accompany MS have been demonstrated to cause chronic low-grade inflammation and to contribute to the pathogenesis of PC 
, it is possible that this is one underlying factors that can be used to explain the associations detected in this study.
Prior epidemiological studies have also provided strong evidence that environmental and dietary factors are important in accelerating the transition between latent and clinically apparent PC. For example, Japanese men experience an increase in the incidence of clinically apparent PC when they move to Hawaii 
, and African men have a much lower incidence of PC than do African-Americans 
. Other studies have demonstrated that a rise in the rate of clinically apparent PC is associated with increased fat intake. They further suggested that this increase may be facilitated by elevated level of androgen production associated with increased fat intake 
. Thus, it is also possible that dietary factors that contributed to urinary changes promoting stone formation also drove hormonal changes which accelerated the pathogenesis of PC.
This study’s strengths include the use of a population-based dataset, which enabled us to trace of all the cases of UC and PC during the study period. The large sample size afforded a considerable statistical advantage in detecting real differences between the two cohorts.
Nevertheless, this study suffered from several limitations that should be addressed. The first limitation is that the diagnoses of both UC and PC relied on administrative claims data reported by physicians and hospitals. These data may be less accurate than diagnoses made according to standardized criteria. Furthermore, as there is no linkage available between this database and the cancer registry, we did not have access to information regarding the stage or grade of PC. This precluded us from conducting any analysis taking these measures into consideration.
Second, some patient information on factors which may have had an effect on the associations detected in this study were not available through the administrative dataset. Some of these factors include tobacco use, alcohol and betel quid consumption, dietary habits, and body mass index.
Third, like many epidemiological studies, this investigation may have been victim to a surveillance bias in which patients with one condition (UC) were more likely to be diagnosed with a separate and possibly unrelated condition (PC) purely based on their increased exposure to the medical community. Therefore, it is possible that more PC cancer was detected among patients with UC due to increased imaging, which may have contributed to the association detected in this study. However, in this study the association between PC and a prior diagnosis of ureter calculus was not significant, discounting the possibility that surveillance bias heavily impacted our results.
Fourth, as this was a case-control study we were unable to comment on causality and were only able to report an association between PC and prior UC.
This investigation detected an association between PC and prior UC after adjusting for co-morbid medical disorders and socioeconomic factors. These results add to the evidence regarding the association between PC and prior UC and highlight a potential target population for PC screening. In addition, it is the hope of the authors that future prospective studies be conducted to establish temporality and to report risk estimates, as well as to elucidate any possible underlying mechanisms between these two conditions