Oesophageal Cancer Gastrointestinal Tract

study,฀current฀cigarette฀smoking฀was฀a฀signiicant฀risk฀factor฀for฀oesophageal฀cancers:฀the฀ association฀ was฀ strongest฀ for฀ oesophageal฀ adenocarcinomas฀ OR฀ =฀ 2.80;฀ CI:฀ 1.8–4.3,฀ intermediate฀for฀gastric฀cardia฀adenocarcinomas฀OR฀=฀2.12;฀CI:฀1.5–3.1,฀and฀weaker฀for฀ distal฀gastric฀adenocarcinomas฀OR฀=฀1.50;฀CI:฀1.1–2.1฀ [305] .฀In฀the฀USA,฀80฀of฀cases฀ of฀ oesophageal฀ cancer฀ observed฀ in฀ the฀ 1990s฀ were฀ related฀ to฀ smoking.฀ Alcohol฀ intake฀ potentiates฀the฀carcinogenic฀effect฀of฀smoking฀ [306,฀307] .฀The฀odds฀ratio฀for฀adenocarci- noma฀of฀the฀distal฀oesophagus฀for฀current฀smokers฀has฀been฀reported฀at฀2.3฀CI:฀1.4–3.9฀ compared฀with฀1.9฀for฀ex-smokers฀CI:฀1.2–3.0.฀Drinkers฀four฀or฀more฀glasses฀of฀whisky day฀also฀have฀an฀odds฀ratio฀of฀2.3฀CI:฀1.3–4.3,฀and฀an฀additive฀effect฀of฀alcohol฀and฀ smoking฀is฀likely฀ [308] .

7.5.2 Gastrointestinal Ulcers

Peptic฀ulcers฀show฀a฀particular฀association฀with฀smoking,฀as฀demonstrated฀by฀a฀wealth฀of฀ publications฀in฀the฀literature฀from฀the฀1950s฀to฀the฀1980s.฀According฀to฀one฀meta-analysis,฀ 24฀of฀all฀peptic฀ulcers฀are฀attributable฀to฀NSAIDs,฀48฀to฀Helicobacter฀pylori฀and฀23฀ to฀ cigarette฀ smoking฀ [309] .฀ Women฀ who฀ smoke฀ are฀ twice฀ as฀ likely฀ as฀ non-smokers฀ to฀ develop฀peptic฀ulcers,฀and฀it฀is฀estimated฀that฀approximately฀20฀of฀incident฀peptic฀ulcer฀ cases฀among฀US฀women฀are฀attributable฀to฀cigarette฀smoking฀ [310] .฀A฀larger฀Polish฀study฀ conducted฀in฀eight฀different฀regions฀underlines฀these฀indings฀ [311] ,฀although฀other฀authors฀ consider฀smoking฀unlike฀Helicobacter฀pylori฀infection฀not฀to฀be฀an฀independent฀factor฀ for฀ulcer฀development฀ [312] . On฀the฀basis฀of฀endoscopy฀indings,฀an฀association฀has฀been฀reported฀between฀cigarette฀ smoking฀and฀Helicobacter฀pylori฀infection฀ [313] ,฀with฀the฀result฀that฀increased฀susceptibility฀ to฀Helicobacter฀pylori฀may฀be฀assumed.฀Gastritis฀caused฀by฀Helicobacter฀pylori฀or฀by฀smok- ing฀is฀associated฀with฀reduced฀concentrations฀of฀the฀intragastric฀epidermal฀growth฀factor฀ EGF,฀a฀substance฀found฀in฀the฀mucosa฀and฀produced฀in฀increased฀quantities฀when฀ulcers฀ develop;฀however,฀this฀growth฀factor฀did฀not฀play฀a฀role฀in฀the฀pathogenesis฀of฀duodenal฀ulcer฀ [314] .฀Experimental฀animal฀work฀indicates฀that฀smoking฀reduces฀EGF-induced฀angiogenesis฀ and฀delays฀ulcer฀healing฀ [315] .฀In฀addition,฀smoking฀depresses฀gastric฀mucosal฀blood฀low฀as฀ well฀as฀the฀production฀of฀NO฀by฀inhibiting฀NO฀synthase฀ [316] . One฀study฀from฀Spain฀in฀Helicobacter฀pylori-positive฀patients฀did฀not฀reveal฀any฀asso- ciation฀between฀Helicobacter฀pylori฀infection฀and฀alcohol฀consumption฀or฀smoking฀ [317] .฀ Smoking฀was฀also฀not฀an฀additional฀risk฀factor฀for฀dyspepsia฀ [318] .฀Where฀smokers฀had฀ successfully฀undergone฀therapy฀to฀eradicate฀Helicobacter฀pylori,฀cigarette฀smoking฀did฀not฀ increase฀the฀recurrence฀of฀peptic฀ulcers฀ [319] . Duodenal฀ulcers฀are฀also฀provoked฀by฀smoking,฀and฀smokers฀have฀been฀reported฀to฀ have฀more฀relapses฀and฀bleeding฀episodes฀than฀ex-smokers฀or฀non-smokers฀63.3฀vs.฀31.2฀ vs.฀34.5฀for฀relapses.฀Ulcer฀bleeding฀occurred฀in฀smokers,฀but฀not฀in฀response฀to฀nicotine฀ intake฀ [320] .฀It฀has฀been฀established฀that฀smoking฀encourages฀the฀development฀of฀duode- nal฀ ulcers฀ by฀ inhibiting฀ duodenal฀ mucosal฀ bicarbonate฀ secretion,฀ an฀ important฀ defence฀ mechanism฀against฀acid฀and฀peptic฀damage฀ [321] .฀Moreover,฀serum฀pepsinogen฀I฀levels฀ are฀elevated฀in฀smokers฀because฀of฀augmented฀pepsin฀secretory฀capacity฀ [322] . Experimental฀animal฀work฀has฀shown฀that฀simultaneous฀cigarette฀smoking฀markedly฀ impairs฀the฀absorption฀of฀cimetidine,฀thus฀attenuating฀its฀eficacy฀ [323] .฀The฀smoking฀sta- tus฀of฀patients฀was฀found฀to฀be฀unimportant฀for฀treatment฀with฀omeprazole฀ [324] .฀This฀ inding฀has฀been฀conirmed฀in฀clinical฀trials฀in฀patients฀with฀duodenal฀ulcers฀ [325,฀326] .

7.5.3 Cancers of the Gastrointestinal Tract

According฀to฀a฀Polish฀study฀in฀741฀gastric฀cancer฀patients,฀smokers฀of฀non-ilter฀cigarettes฀ had฀an฀increased฀risk฀for฀gastric฀cardia฀cancers฀OR฀=฀3.72;฀CI:฀1.35–10.23,฀compared฀ with฀controls฀ [327] .฀Other฀authors฀have฀also฀reported฀that฀smokers฀are฀at฀increased฀risk,฀ particularly฀for฀tumours฀in฀the฀lower฀oesophagusgastric฀cardia฀ [308,฀328–331] ,฀and฀the฀ number฀of฀cigarettes฀smoked฀daily฀is฀also฀important฀for฀the฀increased฀level฀of฀risk฀ [330] .฀ Compared฀with฀non-smokers,฀current฀smokers฀of฀80฀or฀more฀pack-years฀were฀at฀substan- tially฀higher฀risk฀for฀squamous฀cell฀cancer฀OR฀=฀16.9;฀CI:฀4.1–69.1฀ [332] ,฀and฀the฀risk฀ was฀consistent฀with฀body฀mass฀index฀BMI:฀the฀more฀pack-years฀of฀smoking฀and฀the฀ higher฀the฀BMI,฀the฀greater฀the฀risk.฀However,฀smoking฀is฀also฀regarded฀as฀a฀risk฀factor฀for฀ adenocarcinomas฀in฀the฀distal฀gastric฀region฀and฀for฀diffuse฀gastric฀cancers฀ [331] .฀Among฀ patients฀with฀adenocarcinomas฀and฀malignant฀carcinoids฀of฀the฀small฀intestine฀who฀had฀ already฀experienced฀ulcer฀disease฀n฀=฀36,฀compared฀with฀52-healthy฀controls,฀the฀odds฀ ratio฀for฀cigarette฀smoking฀was฀4.6฀CI:฀1.0–20.7฀ [333] ,฀with฀the฀result฀that฀a฀causal฀rela- tionship฀may฀be฀assumed.฀In฀most฀of฀the฀studies฀the฀risk฀was฀further฀increased฀by฀simulta- neous฀alcohol฀spirits฀intake฀ [328] .฀In฀one฀study฀from฀Russia,฀for฀example,฀heavy฀vodka฀ consumption฀had฀a฀potentiating฀effect฀for฀the฀development฀of฀cancer฀of฀the฀cardia฀in฀men฀ OR฀=฀3.4;฀CI:฀1.2–10.2฀and฀for฀cancer฀of฀sites฀other฀than฀the฀gastric฀cardia฀in฀women฀ OR฀=฀1.5;฀CI:฀1.0–2.3฀ [334] .฀While฀carcinomas฀of฀lower฀sections฀of฀the฀small฀intestine฀ have฀been฀linked฀with฀smoking,฀no฀studies฀have฀been฀conducted฀to฀support฀this฀ [335] .

7.5.4 Pancreatic Cancer

According฀to฀several฀prospective฀studies,฀smoking฀doubles฀the฀risk฀for฀the฀development฀of฀ pancreatic฀cancer฀in฀both฀men฀and฀women฀ [336] .฀K-ras฀mutations,฀associated฀with฀alcohol฀ consumption,฀organochlorines฀and฀smoking,฀have฀been฀implicated฀in฀pancreatic฀carcino- genesis฀ [337] . The฀risk฀is฀increased฀ivefold฀in฀people฀smoking฀40฀cigarettes฀daily.฀In฀terms฀of฀tumour฀ development,฀smokers฀do฀not฀attain฀the฀risk฀level฀of฀non-smokers฀until฀10–15฀years฀after฀ smoking฀cessation฀ [336] .฀As฀also฀with฀urinary฀tract฀cancer,฀cadmium฀has฀recently฀been฀ suggested฀as฀a฀factor฀involved฀in฀the฀development฀of฀pancreatic฀cancer:฀during฀smoking,฀ this฀non-essential฀metal฀is฀absorbed฀in฀trace฀amounts฀and฀is฀known฀to฀accumulate฀particu- larly฀ in฀ the฀ pancreas฀ [338] .฀ An฀ Italian฀ study฀ has฀ now฀ shown฀ that฀ compared฀ with฀ non- smokers,฀cigarette฀smokers฀are฀17.3฀times฀more฀likely฀to฀be฀found฀in฀the฀group฀with฀chronic฀ pancreatitis฀and฀5.3฀times฀more฀likely฀to฀be฀found฀in฀those฀with฀pancreatic฀cancer฀ [339] .฀