Kidney Cancer Urinary Tract Diseases

7.6.3 Bladder Cancer

The฀causes฀of฀bladder฀cancer฀are฀to฀be฀sought฀in฀genetic฀changes฀in฀various฀key฀enzymes฀see฀ Sects.฀7.6.1฀and฀7.6.4฀and฀in฀the฀renal฀excretion฀of฀the฀combustion฀products฀of฀smoking. Chromosome฀9฀alterations฀have฀been฀described฀in฀smoking-related฀bladder฀cancer฀ [388] .฀ Half฀of฀all฀kidney฀and฀bladder฀cancers฀in฀men฀are฀related฀to฀smoking.฀According฀to฀an฀Italian฀ study,฀46฀of฀bladder฀cancers฀are฀attributable฀to฀smoking฀ [389] .฀In฀male฀smokers,฀the฀risk฀of฀ bladder฀cancer฀is฀3–7฀times฀higher฀than฀in฀non-smokers฀ [390–392] .฀Among฀women฀37฀of฀ bladder฀cancers฀and฀12฀of฀kidney฀cancers฀are฀smoking-related฀ [393,฀394] ,฀and฀odds฀ratios฀ of฀2.4฀CI:฀1.5–4.0฀and฀2.8฀CI:฀1.2–6.3฀have฀been฀reported฀ [391] .฀Frequent฀coffee฀consump- tion฀has฀been฀cited฀as฀an฀additional฀risk฀factor฀for฀bladder฀cancer.฀Twenty฀years฀ago,฀a฀case– control฀study฀detected฀an฀increased฀smoking-related฀risk฀for฀bladder฀cancer฀in฀men฀RR฀=฀4.8;฀ CI:฀2.4–9.3฀and฀women฀1.7;฀CI:฀1.0–2.7,฀with฀the฀extent฀of฀smoking฀inluencing฀the฀risk฀of฀ cancer฀ [395,฀396] .฀In฀particular,฀heavy฀cigarette฀smokers฀³2฀pack-years฀who฀inhaled฀deeply฀ increased฀their฀risk฀sevenfold฀whereas฀cigar฀smoking฀had฀no฀effect฀on฀the฀development฀of฀ bladder฀cancer฀ [397] .฀Transitional฀cell฀carcinomas฀also฀occurred฀primarily฀in฀smokers,฀with฀ military฀personnel฀being฀at฀greater฀risk฀than฀other฀population฀groups฀ [398] .฀The฀results฀of฀ treatment฀for฀bladder฀cancer฀also฀depend฀on฀smoking฀cessation฀ [399] .฀Differences฀in฀terms฀of฀ increased฀risk฀have฀been฀shown฀between฀smokers฀of฀cigarettes฀OR฀=฀3.5;฀CI:฀2.9–4.2,฀pipes฀ OR฀=฀1.9;฀CI:฀1.2–3.1฀and฀cigars฀OR฀=฀2.3;฀CI:฀1.6–3.5,฀but฀the฀duration฀of฀cigar฀or฀ciga- rette฀ smoking฀ had฀ no฀ effect฀ on฀ the฀ incidence฀ of฀ carcinoma฀ [400] .฀ Non-transitional-cell฀ carcinomas฀are฀reported฀principally฀in฀smokers฀OR฀=฀3.61;฀CI:฀2.08–6.28,฀with฀extremely฀ heavy฀smokers฀being฀at฀even฀greater฀risk฀OR฀=฀7.01;฀CI:฀3.60–13.66฀ [401] .

7.6.4 Cancer of the Cervix

A฀ high฀ proportion฀ of฀ cervical฀ cancers฀ and฀ of฀ cases฀ of฀ cervical฀ intraepithelial฀ neoplasia฀ stage฀III฀may฀be฀regarded฀as฀smoking-related฀ [402–408] ,฀as฀shown฀by฀the฀studies฀from฀ countries฀all฀over฀the฀world.฀Genetic฀polymorphism฀at฀detoxifying฀enzyme฀loci฀such฀as฀ CYP2D6฀ and฀ glutathione฀ S-transferase฀ GSTM1฀ may฀ determine฀ susceptibility฀ to฀ these฀ cancers฀ [408,฀409] .฀Smoking฀is฀an฀independent฀risk฀factor฀ [410] ฀which฀also฀correlates฀with฀ pack-years฀of฀smoking,฀causing฀the฀risk฀to฀increase฀by฀as฀much฀as฀12-fold฀ [411] .฀In฀one฀ case–control฀study฀conducted฀in฀a฀relatively฀large฀population฀in฀UtahUSA,฀the฀risk฀of฀cer- vical฀cancer฀was฀increased฀depending฀on฀pack-years฀of฀smoking฀ever-smokers฀vs.฀smok- ers฀5฀pack-years:฀OR฀=฀2.21;฀CI:฀1.44–3.39฀vs.฀3.42;฀CI:฀2.10–5.57฀ [412] .฀One-third฀of฀all฀ 1,993฀newly฀diagnosed฀cases฀of฀cervical฀cancer฀were฀attributable฀to฀smoking฀ [412,฀413] ,฀ and฀in฀these฀tumours฀too฀the฀breakdown฀products฀of฀smoke฀excreted฀via฀the฀cervical฀epithe- lium฀act฀as฀inducers฀of฀carcinogenesis฀ [413,฀414] .฀Nicotine฀and฀cotinine฀have฀been฀detected฀ in฀the฀cervical฀mucus฀their฀levels฀correlate฀with฀the฀number฀of฀cigarettes฀smoked฀ [415] ,฀ and฀passive฀smokers฀are฀also฀affected.฀In฀particular,฀one฀carcinogenic฀tobacco-speciic฀nit- rosamine,฀NNK฀see฀Sect.฀7.6.1,฀has฀been฀detected฀in฀the฀cervical฀mucus฀of฀current฀smok- ers฀in฀concentrations฀that฀were฀three฀times฀higher฀than฀those฀in฀non-smokers฀ [416] .฀NNK฀ has฀also฀been฀detected฀in฀non-smokers,฀probably฀because฀of฀environmental฀exposure฀ [416] .฀ Smoking฀cessation฀should฀reduce฀lesion฀size฀in฀cervical฀cancer฀ [417] .฀The฀increased฀risk฀for฀ cervical฀cancer฀is฀evident฀from฀the฀data฀presented฀in฀Table฀ 7.6 ฀summarising฀cancer฀inci- dence฀statistics฀from฀a฀follow-up฀study฀conducted฀over฀26฀years฀ [356] .

7.6.5 Prostatic Hyperplasia and Prostatic Cancer

Lower฀urinary฀tract฀symptoms฀have฀been฀reported฀to฀occur฀equally฀in฀various฀age฀catego- ries฀in฀smokers฀and฀non-smokers.฀In฀men฀aged฀40–49฀years,฀the฀symptom฀score฀correlated฀ with฀pack-years,฀with฀urinary฀tract฀infections฀being฀noted฀more฀commonly฀ [418] .฀Alcohol฀ Site฀of฀neoplasm฀ICD–7฀ Number฀n฀ Ex-smokers฀RR฀ 95฀CI฀ Current฀smokers฀RR฀ 95฀CI Total฀140-209 4,023 1.14฀0.95–1.35 1.20฀1.09–1.31 Oral฀cavity฀140-4 46 – 1.60฀0.74–3.45 Pharynx฀145–8 17 – 2.87฀0.85–9.69 Oesophagus฀150 25 3.60฀0.81–15.96 1.68฀0.53–5.25 Upper฀respiratory฀tract฀ 140-8,฀150,฀161 94 0.93฀0.23–3.83 2.14฀1.27–3.61 Stomach฀151 226 0.18฀0.02–1.26 1.25฀0.84–1.86 Colon-rectum฀153-4 559 1.16฀0.72–1.86฀ 0.88฀0.67–1.16 Liver฀155.0 41 – 0.70฀0.24–2.05 Gallbladder฀155.1-155.9 110 0.32฀0.04–2.33 0.66฀0.33–1.34 Pancreas฀157 144 2.47฀1.14–5.34 1.77฀1.09–2.87 Lung฀162.0,฀162.1,฀163 153 1.08฀0.34–3.44 4.82฀3.38–6.88 Breast฀170 996฀ 1.21฀0.88–1.67 0.95฀0.79–1.14 Cervix฀uteri฀171 138 1.01฀0.37–2.78 2.54฀1.74–3.70 Endometrium฀172 248 1.02฀0.52–2.01 0.81฀0.55–1.18 Ovaries฀175 216 1.14฀0.56–2.34 0.93฀0.62–1.39 Kidneys฀180.0 94 1.86฀0.75–4.65฀ 1.09฀0.59–2.01 Bladder฀181.0 102 2.51฀1.08–5.86 2.34฀1.43–3.83 Other฀urinary฀organs฀180.1,฀ 181.1-9 23 – 5.17฀2.03–13.2 Malignant฀melanoma฀190 101 0.89฀0.28–2.85 1.15฀0.68–1.95 Skin฀191 124 1.27฀0.46–3.47 1.14฀0.64–2.00 Brain฀193 122 1.53฀0.66–3.52 1.04฀0.63–1.73 Thyroid฀194 50 0.55฀0.07–4.00 0.98฀0.45–2.17 Non-Hodgkin’s฀lymphoma฀ 200 94 0.66฀0.16–2.69 0.87฀0.43–1.64 Hodgkin’s฀lymphoma฀201 18 – 1.92฀0.56–6.51 Myelomas฀203 71 2.38฀0.85–6.63 1.24฀0.60–2.57 Leukaemias฀204-9 110 1.03฀0.32–3.29 1.24฀0.71–2.18 All฀other฀organs 432 0.87฀0.47–1.59 1.06฀0.80–1.41 Table 7.6 ฀฀฀Relative฀risks฀RR฀with฀95฀conidence฀intervals฀CI฀for฀cancer฀incidence฀in฀the฀period฀ 1964–1989:฀ex-smokers฀and฀current฀smokers฀were฀compared฀with฀non-smokers฀at฀the฀start฀of฀the฀ study.฀The฀data฀were฀adjusted฀for฀age฀and฀place฀of฀residence฀ [356]