Psoriasis Skin and Mucosa

7.8.3 Skin Tumours

The฀development฀of฀squamous฀cell฀carcinoma฀of฀the฀skin฀as฀a฀result฀of฀smoking฀has฀not฀been฀ proven.฀PPP,฀a฀condition฀associated฀with฀immunological฀changes,฀was฀found฀to฀be฀associ- ated฀with฀smoking฀in฀56฀out฀of฀59฀patients,฀all฀of฀whom฀had฀started฀smoking฀before฀the฀onset฀ of฀PPP฀ [507] . The฀development฀of฀squamous฀cell฀carcinoma฀of฀the฀skin฀in฀smokers฀is฀controversial,฀ with฀a฀causal฀relationship฀being฀supported฀by฀some฀published฀evidence฀ [544–546] ฀and฀ refuted฀elsewhere฀ [545–551] .฀The฀risk฀of฀squamous฀cell฀carcinoma฀is฀possibly฀increased฀in฀ men฀over฀the฀age฀of฀60฀years฀RR฀=฀2.01;฀CI:฀1.21–3.34,฀with฀daily฀cigarette฀consumption,฀ duration฀of฀smoking฀and฀exposure฀to฀intense฀sunlight฀being฀crucial฀for฀the฀development฀of฀ the฀condition฀ [546] .฀The฀opposite฀view฀is฀presented฀in฀a฀study฀of฀73,366฀female฀nurses:฀ basal฀cell฀carcinoma฀was฀more฀likely฀to฀develop฀in฀women฀with฀red,฀blonde฀or฀light-brown฀ hair,฀and฀very฀much฀less฀likely฀to฀occur฀in฀women฀with฀naturally฀dark-brown฀hair.฀Risk฀was฀ positively฀associated฀with฀tendency฀to฀sunburn฀as฀a฀child฀or฀adolescent฀and฀with฀the฀life- time฀number฀of฀severe฀episodes฀of฀sunburn,฀but฀not฀at฀all฀with฀cigarette฀smoking฀ [547] .฀ One฀case-control฀study฀from฀1992฀in฀88฀men฀did฀not฀ind฀evidence฀to฀support฀an฀associa- tion฀between฀smoking฀and฀the฀development฀of฀skin฀cancer฀ [548] .฀Similarly,฀no฀association฀ has฀been฀detected฀between฀cigarette฀smoking฀and฀melanoma฀ [549] ;฀however,฀smoking฀has฀ been฀linked฀with฀forms฀of฀anogenital฀skin฀cancer฀vulva,฀vagina,฀cervix,฀anus,฀penis฀ [547] .฀ The฀risk฀for฀the฀development฀of฀carcinoma฀of฀the฀penis฀is฀reported฀to฀be฀increased฀in฀ciga- rette฀ smokers฀ 10฀ cigarettesday฀ twofold฀ [552] ฀ or฀ threefold฀ 45฀ pack-years฀ [553] .฀ More฀than฀50฀of฀women฀with฀cancer฀in฀the฀anal฀region฀are฀smokers฀ [554] ,฀and฀smokers฀ have฀a฀7.7-fold฀increased฀risk฀for฀anal฀cancer฀compared฀with฀non-smokers฀ [555] .฀Cancer฀ of฀the฀vulva฀was฀detected฀when฀10–20฀cigarettesday฀were฀smoked฀for฀more฀than฀20฀years฀ [556–558] . Cancer฀of฀the฀lip฀occurs฀in฀smokers฀generally฀in฀conjunction฀with฀exposure฀to฀strong฀ sunlight฀ [559,฀560] ;฀however,฀other฀authors฀have฀found฀no฀such฀association฀ [561] .฀Heavy฀ cigarette฀smoking฀15฀pack-years฀and฀13฀other฀variables฀were฀tested฀by฀Cox฀multivariate฀ analysis฀for฀their฀ability฀to฀predict฀death฀in฀196฀patients฀with฀clinical฀Stage฀I฀melanoma.฀ Smoking฀may฀be฀regarded฀as฀an฀adverse฀prognostic฀marker฀p฀=฀0.0065,฀and฀melanoma฀ lesion฀thickness฀was฀clearly฀greater฀in฀smokers฀than฀in฀non-smokers฀ [562] .

7.8.4 Breast Cancer

Where฀they฀have฀been฀made฀at฀all,฀assessments฀of฀changes฀in฀the฀female฀breast฀in฀associa- tion฀with฀smoking฀vary฀widely.฀According฀to฀one฀Canadian฀study฀in฀women฀with฀biopsy- conirmed฀ ibroadenoma,฀ cigarette฀ smoking฀ was฀ associated฀ with฀ a฀ reduced฀ risk฀ of฀ ibroadenoma฀RR฀=฀0.66;฀CI:฀0.40–1.10.฀An฀inverse฀correlation฀was฀even฀found฀in฀as฀ much฀as฀the฀risk฀was฀slightly฀higher฀where฀smoking฀habits฀were฀lighter฀RR฀=฀0.49;฀CI:฀ 0.24–0.98฀ [563] .฀Unequivocal฀evidence฀has฀not฀been฀found฀for฀the฀development฀of฀breast฀ cancer฀ in฀ female฀ smokers.฀ Among฀ 2,569฀ women฀ with฀ histologically฀ conirmed฀ breast฀ ฀cancer,฀the฀odds฀ratios฀compared฀with฀women฀who฀had฀never฀smoked฀were฀0.84฀CI:฀ 0.7–1.0฀for฀current฀smokers฀and฀1.14฀CI:฀0.9–1.4฀for฀ex-smokers.฀There฀was฀also฀no฀ increase฀in฀cancer฀risk฀as฀a฀function฀of฀cigarettes฀smoked฀ [564] .฀Similar฀indings฀had฀already฀ been฀reported฀in฀an฀older฀US฀study฀in฀4,720฀women฀with฀breast฀cancer฀OR฀=฀1.2;฀CI:฀ 1.1–1.3฀ [565] .฀Comparison฀of฀the฀incidence฀of฀breast฀cancer฀as฀compared฀with฀that฀of฀lung฀ cancer฀over฀more฀than฀50฀years,฀the฀incidence฀of฀lung฀cancer฀was฀increased฀by฀multiples฀ over฀the฀same฀period฀cf.฀Fig.฀5.1฀in฀Chap.฀5. The฀California฀Environmental฀Protection฀Agency฀CalEPA฀completed฀a฀health฀effects฀ assessment฀of฀exposure฀to฀environmental฀tobacco฀smoke฀ETS฀which฀resulted฀in฀California฀ listing฀ETS฀as฀a฀toxic฀air฀contaminant฀in฀January฀2006.฀As฀part฀of฀the฀assessment,฀studies฀ on฀the฀association฀between฀exposure฀to฀ETS฀and฀breast฀cancer฀were฀reviewed.฀Miller฀et฀al.฀ analysed฀ 26฀ published฀ reports฀ including฀ three฀ meta-analyses฀ evaluating฀ the฀ data฀ and฀ reviewd฀the฀association฀between฀ETS฀exposure฀and฀breast฀cancer.฀A฀weight-of-evidence฀ approach฀ was฀ applied฀ to฀ evaluate฀ the฀ data฀ and฀ draw฀ conclusions฀ about฀ the฀ association฀ between฀ breast฀ cancer฀ and฀ ETS฀ exposure.฀ The฀ published฀ data฀ indicate฀ an฀ association฀ between฀ETS฀and฀breast฀cancer฀in฀younger฀primarily฀premenopausal฀women.฀Thirteen฀of฀ the฀14฀studies฀ten฀case-control฀and฀four฀cohort฀that฀allowed฀analysis฀by฀menopausal฀sta- tus฀reported฀elevated฀risk฀estimates฀for฀breast฀cancer฀in฀premenopausal฀women,฀seven฀of฀ which฀were฀statistically฀signiicant.฀Our฀meta-analyses฀indicated฀elevated฀summary฀rela- tive฀risks฀ranging฀from฀OR฀1.68฀95฀C.I.฀1.31,฀2.15฀for฀all฀14฀studies฀to฀2.20฀95฀C.I.฀ 1.69,฀2.87฀for฀those฀with฀the฀best฀exposure฀assessment.฀The฀CalEPA฀with฀its฀experts฀ concluded฀ that฀ regular฀ ETS฀ exposure฀ is฀ causally฀ related฀ to฀ breast฀ cancer฀ diagnosed฀ in฀ younger,฀primarily฀premenopausal฀women฀and฀that฀the฀association฀is฀not฀likely฀explained฀ by฀bias฀or฀confounding฀ [566] .

7.9 Haematopoietic System

Evidence฀indicating฀a฀possible฀association฀between฀smoking฀and฀the฀development฀of฀leukae- mia฀was฀not฀published฀until฀1986฀ [567] ,฀and฀subsequently฀this฀has฀been฀demonstrated฀not฀ only฀for฀leukaemias฀in฀children฀but฀also฀in฀adults฀ [568,฀569] .฀Several฀cohort฀studies฀ [570–572] ฀ and฀case–control฀studies฀ [568,฀573] ฀focussing฀on฀this฀issue฀have฀been฀published. Genetic฀ defects฀ in฀ NAT2฀ acetylation฀ [574] ฀ or฀ in฀ the฀ cytochrome฀ system฀ CYP1A1,฀ CYP2D6฀or฀CYP2C19฀ [575] ฀has฀no฀inluence฀on฀the฀development฀of฀acute฀myeloid฀or฀ lymphoblastic฀forms฀of฀leukaemia. Results฀published,฀to฀date,฀are฀highly฀contradictory,฀particularly฀because฀several฀studies฀ have฀ reported฀ no฀ association฀ between฀ smoking฀ and฀ leukaemia฀ [576–583] .฀ In฀ a฀ 20-year฀ ฀follow-up฀of฀more฀than฀17,500฀white฀males,฀compared฀with฀non-smokers,฀seasoned฀smokers฀ had฀an฀increased฀relative฀risk฀for฀lymphoblastic฀leukaemia฀RR฀=฀2.7฀and฀other฀unspeciied฀ leukaemia฀RR฀=฀1.5฀ [584] .฀Further฀studies฀have฀conirmed฀that฀smoking฀confers฀an฀increased฀ risk฀for฀various฀forms฀of฀leukaemia฀in฀adult฀men฀and฀women฀OR฀=฀1.5;฀CI:฀1.1–2.0฀and฀1.4;฀