PURPOSE: To investigate the incidence of bladder cancer (BC) in Sri Lanka and to compare risk factors and outcomes with those of other South Asian nations and South Asian migrants to the United Kingdom (UK) and the United States (US). MATERIALS AND METHODS: The incidence of BC in Sri Lanka was examined by using two separate cancer registry databases over a 5-year period. Smoking rates were compiled by using a population-based survey from 2001 to 2009 and the relative risk was calculated by using published data. RESULTS: A total of 637 new cases of BC were diagnosed over the 5-year period. Sri Lankan BC incidence increased from 1985 but remained low (1.36 and 0.3 per 100,000 in males and females) and was similar to the incidence in other South Asian countries. The incidence was lower, however, than in migrant populations in the US and the UK. In densely populated districts of Sri Lanka, these rates almost doubled. Urothelial carcinoma accounted for 72%. The prevalence of male smokers in Sri Lanka was 39%, whereas Pakistan had higher smoking rates with a 6-fold increase in BC. CONCLUSIONS: Sri Lankan BC incidence was low, similar to other South Asian countries (apart from Pakistan), but the actual incidence is likely higher than the cancer registry rates. Smoking is likely to be the main risk factor for BC. Possible under-reporting in rural areas could account for the low rates of BC in Sri Lanka. Any genetic or environmental protective effects of BC in South Asians seem to be lost on migration to the UK or the US and with higher levels of smoking, as seen in Pakistan.
Asian Continental Ancestry Group ; Great Britain ; Humans ; Incidence ; Male ; Pakistan ; Prevalence ; Risk Factors ; Smoke ; Smoking ; Sri Lanka ; Transients and Migrants ; United States ; Urinary Bladder ; Urinary Bladder Neoplasms

AIMTo study the effects of homocysteine and copper on type 5 phosphodiesterase (PDE5) expression in cavernosal vascular smooth muscle cells (CVSMCs) and to investigate superoxide (O(2)(.-)) derived from nicotinamide adenine dinucleotide phosphate oxidase as homocysteine and copper generate O(2)(.-), and O(2)(.-) upregulates PDE5 expression.

METHODSCVSMCs derived from rabbit penis were incubated with homocysteine or copper chloride with or without superoxide dismutase (SOD), catalase, sildenafil citrate, or apocynin (nicotinamide adenine dinucleotide phosphate inhibitor) for 16 h. The expression of PDE5 and of glyceraldehyde-3-phosphate dehydrogenase (internal standard) was assessed using Western blot analysis. In parallel, O(2)(.-) was measured spectrophotometrically.

RESULTSCuCl(2) alone (up to 10 micromol/L) and homocysteine alone (up to 100 micromol/L) had no effect on O(2)(.-) formation in CVSMCs compared to controls. In combination, however, homocysteine and CuCl(2) markedly increased O(2)(.-) formation, an effect blocked by SOD, catalase, apocynin, and sildenafil (1 micromol/L) when co-incubated over the same time course. PDE5 expression was also significantly increased in CVSMCs incubated with homocysteine and CuCl(2), compared to controls. This effect was also negated by 16-h co-incubation with SOD, catalase, apocynin and sildenafil.

CONCLUSIONThis represents a novel pathogenic mechanism underlying ED, and indicates that the therapeutic actions of prolonged sildenafil use are mediated in part through inhibition of this pathway.

Animals ; Blotting, Western ; Chelating Agents ; pharmacology ; Copper ; pharmacology ; Cyclic Nucleotide Phosphodiesterases, Type 5 ; biosynthesis ; Data Interpretation, Statistical ; Gene Expression Regulation, Enzymologic ; drug effects ; Homocysteine ; pharmacology ; In Vitro Techniques ; Male ; Myocytes, Smooth Muscle ; drug effects ; enzymology ; NADPH Oxidases ; antagonists & inhibitors ; Penicillamine ; pharmacology ; Penis ; drug effects ; enzymology ; Phosphodiesterase Inhibitors ; pharmacology ; Piperazines ; pharmacology ; Purines ; pharmacology ; Rabbits ; Reactive Oxygen Species ; metabolism ; Sildenafil Citrate ; Sulfones ; pharmacology