Association between cigarette smoke exposure and urinary bladder cancer in Scottish terriers in a cohort study

Urothelial bladder cancer (UBC) is a disease of significant morbidity and mortality. It is important to understand the risk factors of this disease. To describe the incidence, prevalence, and mortality of UBC and to review and interpret the current evidence on and impact of the related risk factors. A literature search in English was performed using PubMed. Relevant papers on the epidemiology of UBC were selected. UBC is the 7th most common cancer worldwide in men and the 17th most common cancer worldwide in women. Approximately 75% of newly diagnosed UBCs are noninvasive. Each year, approximately 110 500 men and 70 000 women are diagnosed with new cases and 38 200 patients in the European Union and 17 000 US patients die from UBC. Smoking is the most common risk factor and accounts for approximately half of all UBCs. Occupational exposure to aromatic amines and polycyclic aromatic hydrocarbons are other important risk factors. The impact of diet and environmental pollution is less evident. Increasing evidence suggests a significant influence of genetic predisposition on incidence. UBC is a frequently occurring malignancy with a significant impact on public health and will remain so because of the high prevalence of smoking. The importance of primary prevention must be stressed, and smoking cessation programs need to be encouraged and supported. Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Based on the latest GLOBOCAN data, bladder cancer accounts for 3% of global cancer diagnoses and is especially prevalent in the developed world. In the United States, bladder cancer is the sixth most incident neoplasm. A total of 90% of bladder cancer diagnoses are made in those 55 years of age and older, and the disease is four times more common in men than women. While the average 5-year survival in the US is 77%, the 5-year survival for those with metastatic disease is a measly 5%. The strongest risk factor for bladder cancer is tobacco smoking, which accounts for 50–65% of all cases. Occupational or environmental toxins likewise greatly contribute to disease burden (accounting for an estimated 20% of all cases), though the precise proportion can be obscured by the fact bladder cancer develops decades after exposure, even if the exposure only lasted several years. Schistosomiasis infection is the common cause of bladder cancer in regions of Africa and the Middle East and is considered the second most onerous tropical pathogen after malaria. With 81% of cases attributable to known risk factors (and only 7% to heritable mutations), bladder cancer is a prime candidate for prevention strategies. Smoking cessation, workplace safety practices, weight loss, exercise and schistosomiasis prevention (via water disinfection and mass drug administration) have all been shown to significantly decrease the risk of bladder cancer, which poses a growing burden around the world.

While cotinine is commonly used as a biomarker to validate self-reported smoking status, the selection of an optimal cotinine cutoff value for distinguishing true smokers from true nonsmokers shows a lack of standardization among studies. This review describes how the cutoff values have been derived, and explains the issues involved in the generalization of a cutoff value. In this study, we conducted an English-language literature search in PubMed using the keywords “cotinine” and “cutoff” or “self-reported” and “smoking status” and “validation” for the years 1985–2014. We obtained 104 articles, 32 of which provided (1) sensitivity and specificity of a cutoff value and (2) determination methods for the given cutoff value. We found that the saliva cotinine cutoff value range of 10–25 ng/mL, serum and urine cotinine cutoff of 10–20 ng/mL and 50–200 ng/mL, respectively, have been commonly used to validate self-reported smoking status using a 2 × 2 table or a receiver operating characteristics (ROC) curve. We also found that recent large population-based studies in the U.S. and UK reported lower cutoff values for cotinine in serum (3 ng/mL) and saliva (12 ng/mL), compared to the traditionally accepted ones (15 and 14 ng/mg, respectively).