Gonorrhoea and male bladder cancer in a prospective study

Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
British Journal of Cancer (Impact Factor: 4.82). 02/2007; 96(1):169-71. DOI: 10.1038/sj.bjc.6603510
Source: PubMed

ABSTRACT In a prospective cohort study, a close to two-fold elevated risk of bladder cancer was found among men reporting a history of gonorrhoea (relative risk=1.92, 95% CI=1.10-3.33). Our finding warrants further examination of the role of gonorrhoea in bladder carcinogenesis.

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    ABSTRACT: This book is devoted to the role of infectious agents in etiology of human cancer. Over the years of cancer investigation a lot of discoveries in this field were made, and many associations between various biological carcinogens and cancer risk were revealed. Some of them are credibly determined, thus these infectious agents (human papilloma virus, hepatitis B virus, hepatitis C virus, Epsteim-Barr virus, human herpes virus 8, human T-cell lymphotropic virus 1, human immunodeficiency virus, Merkel cell polyomavirus, Helicobacter pylori, Opisthorchis viverrini, Clonorchis sinensis, Schistosoma haematobium) are recognized as carcinogens and probable carcinogens by International Agency for Research on Cancer (IARC). They are not considered in this book since they are perfectly reviewed in a brilliant monograph «Infections Causing Human Cancer» authored by Nobel Prize Laureate Harald zur Hausen. The topic of this monograph is to analyze associations of other infectious agents with cancer risk (thus, it is admissible to call them «unconventional» from the point of view of cancer biologist and epidemiologist). To the best of our knowledge, this is the first book devoted to this problem and highlighting its importance and topicality. Of note, virology is not considered in our monograph: although there are some viruses that can be connected with cancer but are not included into the IARC list (John Cunningham virus, herpes simplex virus-1 and -2, human cytomegalovirus, simian virus 40, xenotropic murine leukemia virus-related virus), we decided to leave them for the virologists and to concentrate our efforts on other infectious agents (bacteria, protozoa, helminths and fungi) since it will better correspond to the conception of this book. Firstly, we note the criteria of inclusion of infectious agents in the list of possible biological carcinogens, and then we briefly describe the general mechanisms of biological carcinogenesis related to the infectious agents analyzed in the monograph (again, we do not concern principles of viral carcinogenesis). In the second part of the book, we review and analyze the available published literature about the possibly carcinogenic infectious agents (firstly bacteria, then protozoa, and, at last, helminths). In the last chapters, we summarize the data about the role of the whole systems of microorganisms (oral and gut microbiota) in the local and distant carcinogenesis. Finally, we wrote some brief conclusions about the role of the «unconventional» carcinogenic infectious agents in cancer etiology, improving the conception of biological carcinogenesis. We prepared this book with the hope that it will be useful for the wide audience, particularly cancer researchers, epidemiologists, microbiologists, PhD, graduate and undergraduate students of biomedical faculties and their lecturers.
    01/2013; Springer., ISBN: 978-94-007-5955-8
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    ABSTRACT: Background: Effective screening and prevention strategies for bladder cancer require accurate risk stratification models. We developed models to predict the risk of bladder cancer based on clinical and sociodemographic factors in participants in the Prostate, Lung, Colon, Ovarian Cancer (PLCO) screening trial. Methods: Baseline clinical and sociodemographic data were obtained from 149,542 PLCO participants aged 55-74 without a prior history of bladder cancer. Cox proportional hazards models were used to predict the risk of all and high-grade bladder cancers (ABC and HGBC) from baseline information. We used the risk model to design a hypothetical bladder cancer mortality prevention trial. Results: Over a median follow-up of 12 years, 1124 men and 259 women developed bladder cancer (including 392 and 72 with HGBC, respectively). The incidence was 133.6 and 29.6 cases per 100,000 person-years, respectively. Nomograms to predict the risk of ABC and HGBC were constructed and the c-indices were 0.746 and 0.759, respectively. Age, race, education, smoking (intensity and duration), comorbidity, prostatitis, syphilis, and hormone replacement therapy use were statistically significant predictors in the models. We show that our risk model can be used to design a BC mortality prevention trial half the size of a trial designed without risk stratification. Conclusion: Models to predict the risk of ABC and HGBC have been developed and validated. Impact: Using the upper 40th percentile from the HGBC model, a suitable cohort for a screening or chemoprevention trial could be identified, although the size and follow-up of such a trial would be costly.
    Cancer Epidemiology Biomarkers & Prevention 10/2013; 22(12). DOI:10.1158/1055-9965.EPI-13-0632 · 4.32 Impact Factor
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    ABSTRACT: Drug-resistant gonorrhea, Neisseria gonorrhoeae (N. gonorrhoeae), is an emerging concern, especially because the risk of bladder cancer is associated with this infection. N. gonorrhoeae suppresses T-helper 1(Th1) and Th2 responses and enhances Th17 responses via a mechanism involving transforming growth factor-beta (TGF-β) and regulatory T cells. Blockade of TGF-β alleviates the suppression of specific anti-gonococcal responses and allows Th1 and Th2 responses to emerge with concomitant boosting of immune memory and protective immunity. Gonorrhea activates nuclear factor kappaB (NF-kappaB), which plays a critical role in signal-transduction pathways involved in inflammation. The innate immune system can eventually clear gonorrhea. Vitamin D is emerging as a potential, powerful, anti-microbial agent with these effects: it supports the innate immune system in combating bacterial infections; it decreases levels of TGF-β and NF-kappaB activation; and it induces production of LL-37 (cathelicidin), which has antimicrobial and antiendotoxin properties. In addition, via an independent vitamin D receptor pathway, curcumin also induces LL-37 production, inhibiting N. gonorrhoeae-induced NF-kappaB signaling and inducing autophagy. Therefore, vitamin D and curcumin taken together may be useful in combating both normal and drug-resistant gonorrhea. Moreover, the possible synergy between these two agents in improving outcomes is worthy of additional investigation.
    Medical Hypotheses 04/2013; 81(1). DOI:10.1016/j.mehy.2013.04.013 · 1.15 Impact Factor


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