Oral and Laryngeal Cancer

serious฀where฀smokers฀hand-roll฀their฀own฀cigarettes฀–฀a฀practice฀that฀is฀still฀customary฀in฀ some฀parts฀of฀the฀world฀see฀Table฀ 7.4 ฀and฀is฀also฀becoming฀increasingly฀common฀again฀ for฀inancial฀reasons฀in฀Germany.฀Contact฀with฀the฀uniltered฀smoke฀and฀its฀constituents฀ damages฀both฀the฀oral฀mucosa฀as฀well฀as฀that฀of฀the฀pharynx฀and฀larynx฀ [224] . The฀increased฀risk฀for฀laryngeal฀cancer฀associated฀with฀excessive฀alcohol฀intake฀has฀ been฀demonstrated฀in฀heavy฀drinkers฀and฀binge฀drinkers฀207฀ml฀pure฀alcohol฀or฀more฀ daily:฀the฀relative฀risks฀in฀these฀categories฀were฀9.6฀and฀28.4,฀respectively,฀compared฀with฀ 2.6฀in฀non-drinking฀smokers฀ [225] .

7.4 Disorders of Lipid and Glucose Metabolism

7.4.1 Lipid and Cholesterol Metabolism

Serum฀concentrations฀of฀triglycerides฀and฀total฀cholesterol฀are฀dependent฀in฀particular฀on฀ dietary฀habits,฀but฀also฀on฀genetic฀factors,฀body฀weight฀and฀alcohol฀consumption.฀Ex-smokers฀ often฀revise฀their฀diet฀to฀include฀more฀vegetable฀protein,฀and฀these฀new฀dietary฀habits฀restore฀ serum฀cholesterol฀and฀lipids฀to฀normal฀levels฀ [226] .฀When฀patients฀at฀increased฀risk฀of฀coro- nary฀heart฀disease฀were฀given฀brief฀behavioural฀counselling฀to฀implement฀lifestyle฀changes,฀ their฀odds฀of฀moving฀to฀actionmaintenance฀of฀behavioural฀intervention฀were฀improved,฀ compared฀with฀control฀patients:฀for฀example,฀fat฀reduction฀OR฀=฀2.15;฀CI:฀1.30–3.56,฀ increased฀physical฀activity฀OR฀=฀1.89;฀CI:฀1.07–3.36฀and฀smoking฀cessation฀OR฀=฀1.77;฀ CI:฀0.76–4.14฀ [227] . Most฀epidemiological฀studies฀ [228] ฀indicate฀that฀smokers฀have฀raised฀triglyceride฀con- centrations฀compared฀with฀non-smokers,฀a฀inding฀that฀has฀not฀been฀conirmed฀in฀long-term฀ Variables Manufactured฀cigarettes Hand-rolled฀cigarettes฀ Patients฀ Controls฀ Patients฀ Controls฀ Age฀years 40–49 5฀14.3 16฀22.2 8฀4.8 10฀6.2 50–59 11฀31.4 15฀20.8 48฀28.9 36฀22.2 60–69 15฀42.9 28฀38.9 80฀48.2 65฀40.1 70–79 4฀11.4 13฀18.1 30฀18.1 51฀31.5 Place฀of฀residence Rural 33฀94.3 67฀93.1 119฀71.7 97฀59.9 Urban 2฀5.7 5฀6.9 47฀28.3 65฀40.1 Education฀years 0–4 16฀45.7 41฀56.9 129฀77.7 124฀76.5 ³ 5 19฀54.3 31฀43.1 37฀22.3 38฀23.5 Total฀number฀of฀patients 35 72 166 162 Table 7.4 ฀฀฀Frequency฀distribution,฀by฀socio-demographic฀variables,฀of฀patients฀with฀cancers฀of฀the฀ oral฀cavity,฀pharynx฀and฀larynx฀compared฀with฀controls฀ [224] studies฀ [229–232] .฀Smoking฀increases฀circulating฀levels฀of฀atherogenic฀LDL฀cholesterol฀by฀ accelerating฀the฀lipid฀conversion฀of฀HDL฀cholesterol฀and฀delaying฀the฀clearance฀of฀LDL฀ cholesterol฀from฀the฀plasma฀compartment฀ [233] . According฀to฀a฀more฀recent฀study฀in฀which฀energy฀intake฀and฀basal฀metabolic฀rate฀were฀ calculated฀in฀205฀women฀and฀141฀men,฀cigarette฀smokers฀had฀a฀higher฀energy฀intake฀from฀ fat฀than฀non-smokers฀29฀vs.฀26,฀a฀lower฀intake฀from฀carbohydrates฀50฀vs.฀54฀and฀a฀ lower฀intake฀of฀vitamin฀C฀11฀vs.฀16฀mg฀ [234] . An฀epidemiological฀study฀conducted฀in฀Westphalia฀in฀several฀thousand฀men฀and฀women฀ showed฀that฀the฀frequency฀of฀subjects฀with฀low฀plasma฀HDL฀cholesterol฀values฀0.907฀ mmolel฀in฀men,฀1.166฀mmolel฀in฀women฀was฀about฀10฀higher฀in฀smokers฀than฀in฀ex- smokers฀ or฀ non-smokers฀ [235] .฀ A฀ study฀ of฀ cardiovascular฀ risk฀ factors฀ in฀ 166฀ cigarette฀ smokers฀revealed฀lower฀serum฀HDL฀cholesterol฀0.76฀vs.฀0.81฀mmolel฀and฀higher฀serum฀ triglycerides฀1.92฀vs.฀1.71฀mmolel฀in฀comparison฀with฀values฀measured฀in฀312฀non- smokers฀ [236] .฀Higher฀triglyceride฀and฀total฀cholesterol฀levels฀have฀also฀been฀reported฀in฀ other฀studies฀of฀smokers฀compared฀with฀non-smokers฀and฀ex-smokers฀ [237–245] .฀A฀meta- analysis฀of฀data฀obtained฀in฀children฀and฀adolescents฀aged฀8–19฀years฀revealed฀associa- tions฀between฀smoking฀or฀non-smoking฀status,฀and฀blood฀lipids฀and฀cholesterol฀fractions;฀ the฀indings฀were฀analogous฀to฀those฀obtained฀in฀adults฀ [228] .฀Plasma฀thiocyanate฀levels,฀ measured฀as฀an฀indicator฀of฀the฀extent฀of฀tobacco฀exposure฀during฀a฀smoking฀reduction฀ programme,฀ correlated฀ signiicantly฀ and฀ inversely฀ with฀ HDL฀ cholesterol฀ and฀ skinfold฀ thickness,฀ but฀ not฀ with฀ LDL฀ cholesterol฀ or฀ triglycerides฀ [230] .฀ The฀ less฀ an฀ individual฀ smoked,฀the฀greater฀was฀the฀increase฀in฀HDL฀cholesterol. Smoking฀during฀pregnancy฀has฀been฀found฀to฀produce฀signiicant฀differences฀in฀various฀ lipid฀parameters฀in฀the฀newborns฀of฀smoker฀mothers฀compared฀with฀the฀newborns฀of฀non- smoker฀mothers: Lower฀HDL฀cholesterol฀21฀vs.฀26฀mgdl •฀ Higher฀total฀cholesterolHDL฀cholesterol฀ratio฀4.7฀vs.฀3.7 •฀ Lower฀apolipoprotein฀A-1฀105฀vs.฀129฀mgdl •฀ Higher฀apolipoprotein฀B฀apolipoprotein฀A-1฀ratio฀0.44฀vs.฀0.3 •฀ Similar฀differences฀were฀also฀detected฀in฀the฀smoker฀and฀non-smoker฀mothers฀ [246] .฀In฀ adult฀ smokers,฀ the฀ deleterious฀ consequences฀ for฀ the฀ coronaries฀ are฀ attributable฀ to฀ the฀ changes฀in฀HDL฀cholesterol฀and฀apolipoprotein฀A-1฀levels฀ [226] . Attempts฀to฀use฀antioxidants฀vitamin฀C,฀a-tocopherol฀to฀reduce฀LDL฀oxidisability฀due฀ to฀ smoking฀ or฀ to฀ block฀ superoxide฀ anion฀ production฀ by฀ leucocytes฀ have฀ been฀ largely฀ unsuccessful฀in฀various฀studies฀ [247] ,฀as฀have฀been฀the฀efforts฀to฀reduce฀raised฀plasma฀ levels฀of฀soluble฀intercellular฀adhesion฀molecule-1฀sICAM-1฀or฀antibodies฀against฀oxi- dised฀LDL฀ [248] . During฀smoking฀cessation฀therapy฀with฀nicotine฀products฀in฀smokers฀attempting฀to฀quit,฀ triglycerides฀ and฀ HDL฀ cholesterol฀ are฀ increased฀ whereas฀ LDL฀ cholesterol฀ is฀ lowered฀ [249–251] .฀ Plasma฀ triglyceride฀ levels฀ after฀ smoking฀ cessation฀ have฀ shown฀ varying฀ responses:฀unchanged฀values฀have฀been฀found฀in฀some฀studies฀ [229,฀232,฀252,฀253] ฀whereas฀ a฀17.2฀reduction฀has฀been฀reported฀after฀6฀weeks฀of฀smoking฀cessation฀ [231] .฀Total฀cho- lesterol฀ rises฀ minimally฀ 2.2฀ [254] ,฀ and฀ HDL฀ cholesterol฀ more฀ markedly฀ 20–30฀