Breast Cancer Skin and Mucosa

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;฀ CI:฀1.0–1.9฀ [568] .฀The฀well-known฀Seventh฀Day฀Adventist฀study฀was฀conducted฀in฀a฀cohort฀ of฀34,000฀subjects฀known฀to฀be฀non-smokers฀on฀religious฀grounds.฀Ex-smokers฀i.e.฀converts฀ who฀smoked฀prior฀to฀their฀baptism฀into฀the฀church฀had฀a฀relative฀risk฀of฀2.00฀for฀leukaemia฀ and฀3.01฀for฀myeloma,฀and฀risk฀increased฀dose-dependently฀with฀increasing฀numbers฀of฀ciga- rettes฀smoked.฀The฀cigarette฀smoking–leukaemia฀relationship฀was฀strongest฀for฀myeloid฀leu- kaemia฀RR฀=฀2.24;฀CI:฀0.91–5.53฀ [572] .฀A฀Norwegian฀study฀in฀26,000฀men฀and฀women฀ identiied฀an฀association฀with฀smoking฀for฀numerous฀cancer฀types,฀but฀not฀for฀leukaemia฀ [585] .฀According฀to฀other฀studies,฀drinking฀habits฀play฀a฀far฀larger฀role฀than฀smoking;฀for฀ example,฀in฀the฀development฀of฀acute฀myeloid฀leukaemia฀ [586] . In฀China,฀smoking฀is฀many฀times฀more฀prevalent฀among฀men฀than฀women฀1฀of฀ young฀women฀smoke฀ [587,฀588] ;฀paternal฀smoking฀during฀the฀preconceptional฀period฀ was฀therefore฀studied฀ [589] ฀because฀the฀role฀of฀maternal฀smoking฀during฀pregnancy฀had฀ already฀been฀investigated฀ [590–594] .฀Controversy฀also฀surrounds฀this฀aspect:฀while฀some฀ studies฀have฀accepted฀that฀an฀association฀exists฀ [586,฀589,฀594–599] ,฀others฀have฀found฀no฀ causal฀association฀between฀maternal฀smoking฀during฀pregnancy฀and฀the฀development฀of฀ childhood฀leukaemias฀ [593,฀597,฀598,฀600–609] .฀According฀to฀Ji฀et฀al.฀ [589] ,฀a฀deinite฀ association฀exists฀between฀paternal฀smoking฀habits฀5฀pack-years฀before฀conception฀and฀ the฀subsequent฀development฀of฀cancer฀in฀offspring฀before฀the฀age฀of฀5฀years.฀Compared฀ with฀children฀whose฀fathers฀had฀never฀smoked,฀the฀children฀of฀fathers฀who฀smoked฀had฀ increased฀odds฀ratios฀for฀the฀following฀cancers: Acute฀lymphoblastic฀leukaemia฀OR฀=฀3.8;฀CI:฀1.3–12.3 •฀ Acute฀myeloid฀leukaemia฀OR฀=฀2.3 •฀ Lymphoma฀OR฀=฀4.5;฀CI:฀1.2–16.8 •฀ Non-Hodgkin’s฀lymphomas฀OR฀=฀1.2;฀CI:฀1.0–1.4฀ •฀ [578] Brain฀tumours฀OR฀=฀2.7;฀CI:฀0.8–9.9 •฀ All฀cancers฀combined฀OR฀=฀1.7;฀CI:฀1.2–2.5 •฀ These฀results฀are฀underlined฀by฀those฀from฀a฀recently฀published฀study฀in฀which฀children฀ with฀low฀birth฀weight฀and฀whose฀mothers฀smoked฀during฀pregnancy฀were฀found฀to฀have฀an฀ increased฀risk฀for฀the฀development฀of฀brain฀tumours฀ [610] ฀and฀acute฀leukaemia฀ [611] .฀The฀ causes฀are฀postulated฀to฀be฀the฀harmful฀effects฀of฀smoking฀DNA฀adduct฀formation฀ [612] ฀ on฀sperm฀cells฀ [595,฀597,฀613] ฀but฀also฀the฀transplacental฀passage฀of฀smoke฀constituents฀to฀ reach฀the฀foetus฀ [614–616] ฀cf.฀Table฀ 7.7 .฀Following฀investigations฀in฀2,359฀cases฀of฀acute฀ lymphoblastic฀leukaemia฀or฀acute฀myeloid฀leukaemia,฀other฀workers฀have฀rejected฀an฀asso- ciation฀between฀the฀development฀of฀acute฀leukaemia฀and฀parental฀smoking฀history฀during฀ pregnancy฀OR฀=฀1.04;฀CI:฀0.91–1.19฀for฀paternal฀andor฀maternal฀smoking฀ [617] . On฀the฀basis฀of฀model฀calculations฀and฀life฀tables,฀an฀association฀has฀been฀established฀ between฀benzene฀inhalation฀by฀cigarette฀smokers฀and฀leukaemia:฀it฀is฀estimated฀that฀ben- zene฀ is฀ responsible฀ for฀ one-tenth฀ to฀ one-half฀ of฀ smoking-induced฀ leukaemia฀ mortality฀ [618] .฀Earlier฀studies฀have฀conirmed฀that฀urinary฀levels฀of฀benzene-related฀compounds฀ e.g.฀catechol,฀hydroquinone฀and฀trans-trans-muconic฀acid฀are฀higher฀in฀smokers฀than฀in฀ non-smokers฀ [619] . Overall,฀evidence฀is฀accumulating฀to฀support฀the฀association฀between฀smoking฀habits฀ and฀the฀development฀of฀cancers฀of฀the฀haematopoietic฀system.