4
    ETS TIMELINE
    1970- SCIENTIFIC RESEARCH PUBLISHED ON EXPOSURE TO VARIOUS
    1980 CONSTITUENTS TO ETS, ANNOYANCE AND IRRITATION EFFECTS OF
    EXPOSURE TO ETS AND ON REPORTED HEALTH EFFECTS ON CHILDREN
    FROM PARENTAL SMOKING.
    197Z THE U.S SURGEON GENERAL STATES: "EVIDENCE IS ACCUMULATING
    THAT THE NONSMOKER MAY HAVE UNTOWARD EFFECTS FROM THE
    POLLUTION HIS SMOKING NEIGHBOR FORCES ON HIM."
    1975 ANTI-SMOKING STRATEGY ANNOUNCED TO "STIGMAT IZE" THE
    SMOKER BY SUGGESTING THAT TOBACCO SMOKE "HARMS" THE
    NONSMOKER.
    1980- PUBLICATION OF FOUR MAJOR STUDIES ON ETS AND CHRONIC
    1981 DISEASE IN ADULTS (LUNG CANCER AND LUNG DISEASE).
    198S FIRST RISK ASSESSMENT ON EXPOSURE TO ETS; PREDICTS 500-
    ,000 LUNG CANCER DEATHS PER YEAR.
    1986 THE U.S. SURGEON GENERAL CONCLUDES THAT ETS CAUSES LUNG
    CANCER IN NONSMOKERS AND RESPIRATORY DISEASE IN CHILDREN.
    1986 U.S. NATIONAL RESEARCH C 0 UNCILI NATIONAL ACADEMY OF SCIENC--
    REPORT ON ETS CONCLUDES THAT THERE IS AN INCREASED RISR
    OF LUNG CANCER AMONG NONSMOKERS FROM EXPOSURE TO ET'~
    j) L', 4H C THE INTERNATIONAL AGENCY FOR RESEARCH ON CANCER (!ARE;
    DETERMINES THAT TOBACCO SMOKE 15 A "CARCINOGEN."
    i988 THE INDEPENDENT SCIENTIFIC COMMITTEE ON SMOKING AND HEALTH
    N THE UNITED KINGDOM ISSUES A REPORT REITERATING THE
    EONCLUSION~ OF THE U.S. SURGEON GENERAL (1986-).
    1990 THE U.S. ENVIRONMENTAL PROTECTION AGENCY ISSU75 A DRAFT
    zl=
    40-1 RTSK ASSESSMENT ON ETS 1N WHICH ETS IS CLASS-IIIED AS A
    "iNOWN HUMAN CARCINOGEN."
    1993 FINALIZATION OF THE U.S. EEPA RISK ASSESSMENT ON ETS.
    U4
    CZ)
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    ETS: HEALTH CLAIMS
    1. EPIDEMIOLOGIC STUDIES
    -8- 2. NO ACTUAL EXPOSURE DATA
    3. BASED ON ARGUMENT FOR BIOLOGICAL PLAUSIBILITY;
    ACTIVE SMOKING IS ASSOCIATED WITH VARIOUS
    DISEASES.
    ETS CONTAINS MANY OF THE SAME CONSTITUENTS AS
    Ms.
    THEREFORE, IT IS BIOLOGICALLY PLAUSIBLE THAT ETS
    CAUSES DISEASE IN NONSMOKERS.
    0
    Lri
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    WHAT is ETS?
    ETS (DF.) : A DYNAMIC MIXTURE COMPOSED OF AGED AND
    DILUTED SIDESTPE.AX SMOKE (SS) AND Z33M"rD
    (is)
    SS: S24OKE FROM TEE BURNING TIP OF THE CIGAR-T==
    XS: = SMOKE TO WHICH THE SHOXER IS EXPOSED
    ETS * SS 0 MS
    BECAUSE OF ITS DYNAMIC NATURE, THERE IS No SINGLE
    CHARACTERIZATION OF ETS. WE ARE ABLE TO SUGGEST WHAT ETS 19 NOT;
    ZT IS NOT EQUIVALENT TO EITHER MS OR SS DUE TO PHYSICAL AND
    QUANTITATIVE CHEMICAL DIFFERENCES:
    PHYSICAL PROPERTY DIFFERENCES:
    BURN TEMPERATURE (MS v SS)
    PARTICLE SIZE
    QUANTITATIVE CHEMICAL DIFFERENCES:
    4800 (XS)/400(SS)/50(ETS)
    DILUTION -- 100x-1000x SS
    0
    L71
    CD
    C\
    11.0
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       M
       Ch ensical Cbar acirrication 7
       Taille 1-1
       CL R"tied and Calculaicd (Cucrin 1987, Calculaitd imm Dat‚ in DIMIS 1987)
       0
       Entiotions for Sidrisrcom Environmirnial 1'uliacto Sniolsc and Curtrol)t…ntting Sidttertain
       go Mainllr‡om EtAissiosi Ratios Iii,le 1-1 Costiftl'eil
       i C9.0f €VAIS A#f,,e.t 0 ~ ~j.,j 3 VAI S JI,t,,t.ge
       (;¯tes c b oonousde, mi il … - 61 1. 1 Guets. 9997 1.7 11 G¯Clirs 198 7
       f-> 49 - 7 1 Il . 0$6 tofootti IVIIII
       -h ivil 092 Il Klug 190 4
       Ajimi 1917 . 4 1 1 198#
       i.hl,.qtl 199,… 1 IO - JA lit#
       Fat  gh 19111il find', Soif!
       1 ls.-ff 11 a 1 1.1 16
       1 6 il Rick,ge lit 1. 1 1 41f It 1149
       0 46 - 61 1 S - 4.7 Mus 1981 mi 0.1 L69falh 1701
       H~t.0.4 &Cid 370 - 680 faiauth 198P
       Cigt-os, ma 1 il 640 Gurfigs 1917 Nfigic ocid J - 41 F640.8h 1981
       J70 170 Ad.mb 1917 Mcibylamint 71 la 4 4.1 6.1 $Šk,ƒmŠ 19146
       410 760 LI il Klug 191J Dimcthyl4minc 19 31 J.7 J.1 Sobume Illis
       (1) 1980
       9 y 7 e 1.0p.0pyltine 10 - Il 4~1 - 7-0 S.Iuma IMe
       Nafogrn Osides, me Cutisrs 1997 llyd.08ca tyonide 4 le - lui 0 17- 0. 17) Guetin 89111P ,
       C) J a - 2 6 li‚. l9N9 17 006- 0 14 10.6 1181
       1.0 Il ilimv 0 l‚- 0 49 111)
       1 - 1 0 1 'est. ® . IV16 PlutitiC6 1.101 tu.61, 1 76 1.) - 1.9) G l. 1981
       1.4 - 210 1.7 - 1.1 %lui MI
       1.0 4.4 43- 9.5 Nf.,…b 198 19 Ji il a.b4>ne
       Marogers diamide. mg 01 0.) F~sf.jh 1909 1187
       il di 13 - 1.9 G-flh stol
       .8 10.4 1 S 44 - 7J Cutoi. 1907 Il 14 1.1 - 17 Adams Il‚o?
       0 0.1 0.9 L9 - 16 Aj…nt‡ IVN7 IPSI
       01
       1 l'O falough 1999 0,1110
       fq- 1 Il A 17 - 61 sbkufla 11#41$ 9 10 8946
       1.1 - 8 1 Ila -170 Klug Viol 16 - 16 ut - il Igtckcql ltoi
       J 1 - 5 8 44 - 7) h'un.t n il - 19 04 - JA ICI.b %loi
       10 1180
       i 0) N-04M Micsant, mi (0.2 - 7.6 2.6 - 3.31 Cultin 1917
       01,
       foumaldghyde. mi 11.0 - 4.6 J 1 Gardes 1997
       ghigath 110119
       1987
       ID 1.1 $1 Mus i Vol 1.1 6.1 1919 1
       CL Actiont, mg ro 4 K1.1 lgil 3.1 110119 l
       06 - 1.0 ).9 - 3.4 Ictus 1982 1.6 - Ti 1.6 G.Clin lysl
       0
       04.
       0

       


       0 i

       


    EXPOSURE TO ETS
    PUBLISHED STUDIES INDICATE THAT NONSMOKER EXPOSURE TO
    ETS UNDER 'NORMAL, EVERYDAY CONDITIONS IS MINIMAL. FOR EXAMPLE,
    RESEARCHERS REPORT THAT THERE IS LITTLE DIFFERENCE IN AMBIENT LEVELS
    OF CARBON MONOXIDE IN SMOKING AND NONSMOKING AREAS OF WORKPLACES
    AND PUBLIC PLACES. OTHER STUDIES INDICATE THAT ETS CONTRIBUTES
    LESS THAN HALF OF THE TOTAL PARTICLES IN THE AIR OF AN AVERAGE
    PUBLIC PLACE- NICOTINE OFTEN IS USED AS A MARKER FOR ETS EXPOSURES
    BECAUSE IT IS UNI(IUE TO TOBACCO SMOKE. TYPICAL MEASUREMENTS OF
    NICOTINE RANGE FROM AN EXPOSURE EaUIVALENT OF I/100TH TO I/1000TH
    OF ONE FILTER CIGARETTE PER HOUR- THIS MEANS THAT A NONSMOKER
    WOULD HAVE TO SPEND FROM 100 TO 1000 HOURS IN AN OFFICE, RESTAURANT
    OR PUBLIC PLACE IN ORDER TO BE EXPOSED TO THE NICOTINE E(IUIVALENT
    OF A SINGLE CIGARETTE.
    CD
    -T- (a U-j
    CD
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    7kRGUMZNT FQR BTOLOQTC&L PLA1DS1BZL::Ty
    -XS-SS-ETS ARZ CIMMCA=Y SIXILAR XIXTURES
    -MS and SS CONTAIN CARCINOGENS
    -ETS ALSO CONTAINS CARCINOGENS
    (IMPLIC17 ASSUMPTION: 711JERE IS 110 JERESEOLD FOR EXPOSUPE TO A
    CARCINOGzN)
    ~JA
    10802250
    -V. ~
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    1. a ITITF Ly 0-- Al"
    This Hoffma= and Hecht list ("rbe list of 43- in Table 5) ca=lop the u)ba= and/
    fabac= =0ke CDMPCX=ts -1-s6 as "Mmoripaic agents" and the pC: cipreMe MZ and!
    &Ii~s of each.
    - ABI-E 5. "TIM 1=7 OF 43*'.* ®TUbK¯3ENIC AGENn IN TOBACCO Aj~
    TOBACCO S)4OŒM"
    aie Fm c…0~ bc p- cw-
    Dl…mrr Lamb DOWMY La"…
    L~ Me U-4- M.- c¯ Law Mo uni,
    l'Aku ^Rab"= ……œDiEs
    CI …M~drwBMM®M 20 ®¯ et :5 >Irobmmw 30 2M mg
    = ne 26 2,vaf"5, 1 ZI nt
    21 au :7 bwbm) 4-*wM~ : 3 et
    04 6 112 et ALDEffyou
    C5 40 et 29 10
    Ao 60 et 2t 18 lam gg
    4 lu ¯ le 20 01
    Ca fr"uw or 1.7 3.2 me bOSCELLAMBOM
    ommwd,wb-mw-)
    4 20 ut =
    C~s et 33
    AZA-ARM = 34 Fi 0.13 1221 pq
    1'. Q6i--'dm 1 2 pu 25 1Nb~4 BC
    13 " 1 et isv…"d
    14 90 au BOOW.-AtfK
    CXIWFCNqENn
    15 73-z>Š-.d g 0.7 qu 37 - 1 24 43 nt
    38 lx et
    39 690 et
    17 3 12 40 c…~ 4M BC
    il ND 25 ut 41 cw…¯~ 41 42 oc
    19 1.5 110 et 42 LMA 25 113 et
    19 No 36 et 43 0.0 1.0 pci
    *1 1"~ ' ,
    . 1 0.12. 3.7
    = 410w,16~Ybi¯mmm¯>.]-c3- 0.019 W'7~q
    ?YSd7r1j-b~ ND *--d
    23 jrw~ 0.14 4.6 pq
    24 ND
    €-r-
    CD
    CD
    BATCo document for Legal Services : Health Canada 20 October 1999

    




    11THE LIST OF 4316
    MOST DETERMINATIONS WERE NOT BASED UPON INHALATION STUDIES OR
    UPON DOSES COMPARABLE TO MS
    FIVE OF TEE 43 CONSTITUENTS PRODUCED RESPIRATORY TRACT TUMORS
    V=.A. INHALATION  4-5.
    FOUR WERE NOTED "EQUIVOCAL" BY TEE RTZCS
    ONLY ONE CONSTITUENT HAS BEEN RATED "UNEQUIVOCAL"
    FOR INDUCTION OF TUMORS VIA INHALATION: POLONIUM
    210
    LIFETIME EXPOSURES OF EXPERIMENTAL ANIXALS To
    WHOLE-SMOKE HAVE NOT GENERATED SQUAMOUS CELL
    CARCINOMAS
    TE-REE ANIMAL INHALATION STUDIES ON SS RAVE BEEN
    PUBLISHED TO DATE (2 SUB-CHRONIC, I LIFETIME). NO
    POSITIVE RESULTS WERE REPORTED FOR ANY STUDY
    p-,~/ ; ~
    ,- 4- J^
    0
    REGISTRY OF TOXIC EFFECTS OF CHEMICAL SUBSTANCES
    T~r,
    CD
    CD
    __j
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    DETERMINATION OF DOSE: COTININE
    IT HAS BEEN REPORTED THAT COTININE, A SUBSTANCE CONVERTED FROM
    NICOTINE BY THE BODY, CAN BE USED AS A BIOLOGICAL MARKER TO
    MEASURE NONS14OKER EXPOSURE TO ETS. WHILE SOME REPORTS SUGGEST
    THAT COTININE IS A RELIABLE MARKER FOR TOTAL EXPOSURE TO
    TOBACCO SMOKE, MANY OTHERS 00 NOT. RESEARCHERS HAVE REPORTED
    THAT INDIVIDUALS METABOLIZE NICOTINE IN DIFFERENT WAYS AT
    DIFFERENT TIMES AND THAT ELIMINATION RATES FOR COTININE VARY
    AMONG INDIVIDUALS- IN ADDITION, RECENT RESEARCH- INDICATES
    THAT DIET MAY CONTRIBUTE TO LEVELS OF NICOTINE AND COTININE
    FOUND IN THE BODY, THEREBY INTERFERING WITH AMBIENT AIR
    EXPOSURE LEVELS- SCIENTISTS HAVE ALSO NOTED THAT DIFFERENT
    METHODS OF ANALYSIS MAY INFLUENCE FINAL RECORDED LEVELS OF
    COTININE. AND FINALLY, BECAUSE COTININE IS A METABOLITE OF A
    GAS-PHASE CONSTITUENT OF ETS, NICOTINE, COTININE LEVELS DO
    NOT REPRESENT EXPOSURES TO OTHER CONSTITUENTS OF ETS.
    Lri
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    IN CONCLUSION, COTININE IS NOT A RELIABLE (IUANTITATTVE MEASURE
    OF ETS EXPOSURE. THIS IS BECAUSE BODY FLUID LEVELS OF COTININE
    CANNOT BE ATTRIBUTED SOLELY TO NICOTINE IN ETS, AND BECAUSE
    BODY FLUID LEVELS OF COTININE DO NOT CORRELATE WELL WM ACTUAL
    AMBIENT AIR EXPOSURES TO ETS OR WITH ETS CONSTITUENTS Orr[ER
    THAN NICOTINE. AT BEST, COTININE MAY BE USED AS A QUALITATIVE
    MARKER OF AMBIENT NICOTINE EXPOSURES.
    0
    Lri
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    DETERMINATION OF DOSE: LUNG RETENTION
    COTININE IS A BIOLOGICALLY INACTIVE SUBSTANCE WHICH HAS NOT
    BEEN CORRELATED WITH ETS CONSTITUENTS RETAINED IN THE LUNG.
    SEVERAL RESEARCHERS HAVE ESTIMATED LEVELS OF ETS PARTICULATE
    UPTAKE BY NONSMOKERS TO APPROXIMATE 0.02% (TW-HUHDREOTH OF
    ONE PERCENT) THAT OF THE PARTICULATE EXPOSURE OF AN ACTIVE
    SMOKER.
    REFERENCES
    ARUNDEL, A. AND WEINKAM, J., "NEVER SMOKER LUNG CANCER RISKS
    FROM EXPOSURE TO PARTICULATE TOBACCO SMOKE," EhVIRON- TNT.
    13: 409-426, 1987.
    ADLKOFER, F., "BIOLOGICAL EFFECTS AFTER EXPOSURE TO ETS,"
    INDOOR AIR GUALITY: SYMPOSIUM (BUENOS AIRES: NATIONAL ACADEMY
    OF SCIENCES OF BUENOS AIRES, 1989): 61-76.
    MCAUGHEY, J-, ET AL-, "RESPIRATORY DEPOSITION OF ENVIRONMENTAL
    TOBACCO SMOKE," THE FIFTH INTERNATIONAL CONFERENCE ON INDOOR
    AIR QUALITY AND CLIMATE (TORONTO, CANADA, JULYIAUGUST 1990:
    361-366.
    COMMENTS OF THE R.J. REYNOLDS TOBACCO COMPANY ON APPENDIX C
    TO THE DRAFT RISK ASSESSMENT OF THE EPA - DOSIMETRY OF
    ENVIRONMENTAL TOBACCO SMOKE, SEPTEMBER 1990, B-1 - C-7.
    C:)
    CD
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    7,.qr ETS ISSUE
    " ~ ~ "r,;ja 'I
    ICEA-L-TE CLAZRS: J41Y - I " ,
    *L--.-.1vG CANCER (34)
    *OT=- R CANCER (is)
    *C;LRD-10VASCULAR DISEASE (12)
    PRE-EXISTENT EEART CONDITIONS (E.G. ANG761M)
    (2+)
    (0,:HEp 'N -- N
    TF.AN CANCER) AND  UNCTIM
    *A:)ULTS (I-)
    PR-Z---X'-~STZNT LUNG DISEASE (E.G. ASTHYA)
    (10)
    *-LDRE"q (Gi0o+)
    CH=
    4. EXPOSURE EFF=Ts
    ALLZRGY
    :RR~zTA--I0N/;0W0YANCM
    S~-C'.K-BUILMING SYNDROME
    *BASED UPON E?::MM:'-L3G.-C S::=:--S.
    1=223;
    (-r,
    CD
    c::>
    -_j
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    CXSZ-CONT.ROL STUDIES
    CO:1(PARZ THE EXPOSURE HISTOR:ZS OF TWO KATCZED GROUPS: A GROUP
    OF TNZrZVZDUALS IMO RAVE A DISEASE ("CASES"), AND A GROUP WHO
    DO NOT EAVE TEE DISEASE ("CONTROLS").
    RZSTS ARZ. CEARACTERZZED BY TEE ODDS RX-.10 (T-23 ODDS FOR
    DISEASE OCCURRENCZ IN "IME CASES, DIV'IDED BY TEE ODDS 7OR
    DISEASE OCCURRENCE IN TEE CONTROLS) .
    DZSEASM ODDS RATIO, OR
    EX?OSED UN"EXPOSED
    rd Z.11 SZ
    NC ::ZT_A5__ C
    :14 07 MISEASE IN =POSEZ, A/C AXZ
    7SEASE 11; NON-®2'XPCS--D, B/D
    O= --A-~ZR 0-7 ZZ EXC
    9
    I Gs::-- I
    (J-1
    CD
    CD
    _Z
    BATCo document for Legal Services : Health Canada 20 October 1999

    




    REPORTED RISK ESTIKATES FOR SPOUSAL SMOKING
    STUI)y GENpER RR
    1. WU-W:LLIAMS F 0.70
    2. L:u F 0.74
    3. CHAN F (0.75)
    4. B U F;r: E;z F 0.78
    S. KABA-, T F 0.79
    6. GAO F 0.9
    7. KABAT 11 F 0.90
    8. JANE FZ: CH M, F 0.93
    9. SOSUE F 0.94
    0 10. BROWNSON Il F 1.0
    11. LEE F 1.0
    12. SH:Mrzu F 1.1
    13. Du F 1.19
    14. P E;Z SH A G Z N F 1.2
    15. Wu F 1.2
    16. SVENSSON F 1.20
    17. , FIONTHAM F 1.21
    is. GARF'~'NKEL II F 1.22
    19. GARFZNKEL i F 1.27
    20. p jaA YAMA F 1.45 *
    21. AK7-=A F 1.5
    22. STOCKWELL F 1.6
    23. Koo F 1.64
    24. LAM F 1.65 *
    BROWNSON I F 1.68
    ~-:UM= LIT P~, F 1.8
    27. LAm *~"=-, F (2.01) *
    28. BUTLER F 2.04
    29. CORREA F 2.07
    30. KA LA NC -- C I F 2.11 *
    31. G---NG F 2.16 *
    32. -TNOUE F Z.Z5
    33. TR:CHOPOULOS F 2.4
    34. HOLE M,F 2.41
    STA7:STICALLY SIGNIF.ICANT ~_rl
    CD
    cc
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    ETS AND LUNG CANCER
    THE DATA: 34 PURLZSHED SPOUSAL SMOKING STUDIES
    (4 COHORT; 30 CASE-CONTROL)
    0
    NULL HYPO7~-;ESIS: THERE IS NO ASSOC:ATION BETWEEN ETIS EXPOSIJRE AND
    LUNG CANCI-R IN NONSMOKERS.
    STATISTICAL
    SIGN17ICANC-7: SIX OF 34 STUDIES REPORT RISK ESTIMATES THAT
    SUPPORT REJECTION OF THE NULL HYPOTHESIS
    THE MAJOR17Y (28 0-- 34) ARE CONS7STEJNT WITH THE NULL FYPOTHESIS OF
    NO ASSOCIATION.
    (a
    CD
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    GEOGRAPHIC DISTRIBUTION
    UN-- T--D
    ASIA2
    STA-j -S  EUROPE!
    BROWNSON I CILLIS AK13A
    B;zowNsON II KALANDIDI*  CHAN
    BUFFLER LEr Du
    BUTLER PERSHAGEN CAC
    CORREA SVENSSON GENG*
    FON-,HAK TR::HOPGULDS* HIRAYAMA*
    GARFINKEL I INOUE
    GARF-iNKEL I! Lru
    HUMS,-- K;0
    JAN ER: CH LAM 11,
    KABAT I LAM II*
    KASAT II SHIMIZU
    STOZ"ELL SOSUE
    wu WU-WILL:AMS
    -STATIS-i::ALLY SIGNIF::AN7
    0
    1. GREA7 ERITA:N (2) ; GREEcE (2) ; SWEDEN (2)
    2. CmiNA (5); HoNG KONG (4); JAPAN (5)
    - - M,,~q 4,r, -,4,zz -41- , -, 4., / 071".ec-
    ~1 d,~ '? X~, :Z,l ( ~~ - r-t~
    (-r-
    CD
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    11\j
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    WORKPLACE ETS EXPOSURE
    FOURTEEN OF THE SPOUSAL SMOKING STUDIES HAVE INCLUDED ESTIMATES OF
    EXPOSURE TO ETS IN THE WORKPLACE. IN THOSE 14 STUDIES, THERE ARE
    1S R:SK ESTIMATES.
    TWO OF THE IS REPORTED RISK ESTIMATES ARE STA71STICALLY
    ONLY
    S:GNIFICANT.
    THE RAJORITY (16 OF 18) ARE CONSISTENT WITH THE NULL HYPOTHESIS OF
    NO ASSOCIATION.
    (..ri
    c- Iri CD
    C:D
    0D
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    REPORTED RISK ESTIMATES FOR WDRULACE EXPOSURE
    STUDY GENDER RR
    1. STOCKWELL F NS
    2. BUTLER M 0.0
    3. LEE F 0.63
    4. KABAT I F 0.68
    5. GARFINKEL 11 F 0.88
    6. JAMERICH M,F 0.91
    7. Koo F 0.91
    8. KASAT II M 0.98
    9. KASAT II F 1.00
    10. KALAND:DI F i.08
    1". WU-WILLIAMS F
    IL . BROWNSON 11 F 1.2 1
    1". SHIMIZU F 1.2
    1:' Wu F 1.3
    ONTHAM
    10 FQ F 1.34
    16 . 8 LITLER F 1.47
    17. LEE M 1.61 i
    is. KAEAT I M Z7
    STATISTICALLY SIGNIFICANT
    M ~, (~ - , I C% l-f 4~1 U-cf! le 9 1 1 ~,fC ~;
    JEN
    (-r,
    (7D
    CD
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    X-~
    BATCo document for Legal Services : Health Canada 20 October 1999

    




    ETS EXPOSURE DURING CHILDHDDiD
    THIRTEEN OF THE SPOUSAL SMOKING STUDIES HAVE INC-IUDED AT LEAST ONE
    ESTIMATE OF EXPOSURE TO ETS DURING CHILDHOOD. AT LEAST ZO RISK
    ESTIMATES ARE PRESENTED.
    0
    ONLY Twc OF 20 REFOR-iED RISK ES-tZMATES ARE 57ATIS-ilCALLY
    S-AGNIFICAN7.
    T
    1HE MAJOR-7-1-Y (18 OF 20) AREE CONSISTENT WITH THE NULL HYPOTHESIS OF
    NO ASSOCIATION.
    Lri
    CD
    CD
    Co
    (-n
    BATCo document for Legal Services : Health Canada 20 October 1999

    




    REPORTED RISK ESTIMATES FOR 0ILDHOOD EXPOSURE
    STUDY GENDER RR
    1. AKIBA M,F NS
    2. CORREA M,F NS.
    3. SOSUE F 0.60 (FATHER)
    4. Wu F 0.6
    0 5. BROWNSON F 0.7
    6. KA13AT 11 ?A, 0.73
    7. FoNTHAM F 0.82 (FATHER)
    FoNTHAM F 0.84 (MOTHER)
    SVENSSON F 0.9 (FATHER)
    10. GARFINKEL Il- F 0.9i
    11. JANERICH M,F 1.09(7-24 S-Y)
    12. GAO F 1.1
    13. STOCKWELL F 1.2 (FATHER)
    Koo F 1.21
    1:-. STOCKWELL F 1.6 (MOTHER)
    '16. KABAT TT F 1.68
    17. SOSUE F 1.71 (MOTHER)
    .18. JANERICH M,F 2.07 (23+ 5-Y) *
    19. STOCKWLL' F 2.4 (Z-% S-Y) *
    20. 5 V zN S S 0 N r 3.3 (MOTHER)
    w STAT:S77-CALLY SIGNIFICANT
    0
    CD
    cc
    C71%
    BATCo document for Legal Services : Health Canada 20 October 1999

    




    CONFOUNDERS
    AND
    INDEPENDENT RISK FACTORS
    I-VIOUAL NUTR-"-EN7,S OR FOODS
    HEALTH--EA" DIETS
    C:--,3K!NG PRACT_7~-7_S
    S7.7-R FRY:NG AND DEEP FRYING
    H-:.~7--'.NG FHE-15
    COAL, KERCSENE, WOOD AND STRAW
    P---R-SONAL MEDICAL F-IS701-Y
    LUNG DISEASEE
    F,~',"-7-; Y M -: D 11, C A" L H'--, S Ti 0 r- Y
    LUNG CANC~-R
    OCCUPATIONAL EXPOSURES
    Lr‚
    C:D
    CD
    CQ
    ---.…
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    ----------
    R4&t ƒmers fer lest om®r.
    salope".,
    Eau" a anm=w= 1= Cla - Ir-l) Wu et &L 19U 1
    &_' (Ij - $4-4) MMM cg e. 19r.
    6.4 t---m et &L MS
    1-7 r.80 a al. 19r,
    J‚w%j Mac= 3.9 Wei a &L 19"
    …i Sam= a al. Lffl
    Josaie
    œgr. =~=V= I!L =U= :.4 (p < = bw…cr Mg 1
    es Vz. &ca‡t=t,=c =w= Z,4
    - ..-.: U (LI - ®M-1r)
    = C1.0 - 1:, ) GOED et &L 19r,
    Gao CI ai - 19r, …
    prnmmoria L?
    …tat au=4 -~--*…ccd 1.9
    w‡ccec q&V Cs
    cW0 et AI. 197
    ho-nz:%e r- w-=:n li ^au&& ci al. 1989
    xcc;Lr.t PC: 01 Houx et &J. M&
    -ccc=l MCLZ.=- d-3 kiurnior-- et j~- 19r,
    -=c = =2- Suu= 197-.
    Cr
    K= 19U
    Gao
    Lat inu-4- l9z,
    por4 M
    -- (I®Z - !.œ. Ger% and wj.M1e~ 19CI
    trezz …t~ -- Mc U; 1.6 ltytarazr Y-az 199r,
    BLOC 196A
    aloi 19&4
    1-6 (li-. - L3', CI
    W--4= CL:a= - Ha?= ci &L
    L'n~bt VL r=. -36L MLC 3h~ 19"
    Immœ au der 199:
    -L au Lkr 1991
    Dm.vr=-- -- suuC7. 199,
    la a wxXL: LISEPA 199C
    USXRC 1986
    " (M.i - CLU-J Gon and Migile 1991
    t-r' bir"r'. et L. lm-
    ir" ¯~." - L… €.*. - X= 19U
    …4t~ ¯.D= --&&= A inuit CM e - K,%Je et al. 19r-.
    brca--z . - Av=œ ail e-% - 0M) Menun et L. 19V.-*
    vere.xl-n =.I.L: C.3 (p - QM€ trmd) Gon &nd M&ntc.' 1991
    WI: 15E!
    C.Cr. …z~t M.Ute! 199)
    M IT,-
    BATCo document for Legal Services : Health Canada 20 October 1999

    




    SIAS
    EXPOSURE MISCLASSIFICATilON
    - NO ACTUAL EXPOSURE DATA
    - QUESTIONNAIRE$ ARE USED
    - RECALL BIAS
    - CASES AND CONTROLS MAY REPORT EXPOSURES DIFFERENTLY
    - RESPO-NSES MAY VARY AMONG GROUPS OF SURROGATES
    ",SEASE MISCLASS-7FICATION
    - LO.~ LEVELS OF HISTOLOG:CAL CONFIRMATION
    - PRESENCE OF LUNG CANCER
    - PRIMARY VS- SECONDARY TUMOR
    V,,TSCLAS.- I TON
    -MOKING STATUS SIFICAT_
    SOME SMOKERS MAY BE MISCLASS17:ZED AS NONSMOKERS
    TH-~S MAY ACCOUNT FOR ELEVATED RISK ESTIMATES (P.N. LE=-)
    PUBLICAT-70N BIAS
    '0 -
    -URNALS MAY PREF REN,"ALLY PUBLISH POSITIVE STUDIES
    - AUTHORS MAY NOT SUBMIT NEGATIVE RESULTS (FILE DRAWER
    PHENOMENON)
    ~-r4
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    (-^l
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    ~10
    BATCo document for Legal Services : Health Canada 20 October 1999

    




    A XAjCR SOURCZ Or BIAS
    ZXTEXSjVz- USE 0-. UNRELIMLE QUESTIONWAZIMS rO XSSESS ZTS EX20SURE.
    RzSP0=Z'.IIIT RR
    STUDY S-w-WEC". -1.00
    NUSBAUM 0.92
    SON/DAUGHTER 3.1-9
    OTHER 0.77,
    Gazfin.kel, et &I ~-985 i
    105CZ255
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    BATCo document for Legal Services : Health Canada 20 October 1999

    




    =/Eet= D,serse Relzit4ve Risks
    Relative
    R" Sk
    2) Dc'--scn, at a!. M 57
    (1991) 2.46*
    M
    6  ('Wc=k)
    2) Garland, a= a- 2.7
    4) He, a'= al .
    5) Helsinq, at a: Y. 2 -.
    12; 4 ra va=a 'F -
    -a' a, at a!.
    Lee, at 2.1.
    (:.9
    -0) Mz=,n, at al.
    Pal=er, at al. F
    . 2) Svendsen, et al. M 2.2
    (2.987)
    *R.ezcrted tz be signiticant a-t t~je q!% -leve*cf
    Lr.
    c:~
    110
    BATCo document for Legal Services : Health Canada 20 October 1999

    




    P=Llrts Re P--i=a--y Epidem-iologi=1
    Reports on LITS/Heart, Disease
    Orly f ive --f 12 (less t~harj 1/2) StUdies  repcr=
    "y
    staz-~smi=a , risk.
    2. Three c:f the five were very s=aII-scale.
    2. The ot-her V-7c have =ajc= f1aws, S-azh as weak ---,:S
    ex,=osure esti=ates, pCtent--al ccnf=un="-'
    ar'd
    - :4 dl A -~
    C
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    BATCo document for Legal Services : Health Canada 20 October 1999

    




    CHILDHOOD STUDIES
    SiUD---S THT HAVE E' MINED RESPIRATORY DISEASt-~i ANU
    CONDI'T70NS IN F~ILDRE`N HAVE B CONSISTENT AND VARTABLE IN THE
    PARAI~
    E~l --- R S qE.-ASURED. - STUDIES -EUALLY LOOK AT 04--- OR A-cOREINATION
    OF SEVERAL OF THEE PAPAMETERS LISTED BEELOW:
    COUGHING
    WHE77ING
    SNE-!7IXG
    SNORING
    DIAGNOSIS OF LRI OR URI
    THE STUDIES FALL INTO FIVE OR SIX BROAD CATEGORIES:
    RESPIRATORY SYMPTOMS
    COMPROMISED CHILDREN
    LUNG FUNCTT
    ON
    OTITIS MED1.1, i
    -is
    OTHER (MROPSYCHOLOGICALIBEE.
    ..AVIOR, ETC.)
    (_4
    ~10
    (-p4
    BATCo document for Legal Services Health Canada 20 October 1999

    




    PARFTAL SMX?e AND
    RE--:Z.~TORY EAL7jH IN SC-W- AGE MoeL'rEli
    T y BR34-
    C¯EMN Er ju-
    COLL-ry
    L-Em.-,,z ¯c
    ET AL.
    L-O.YD L7 A.L.
    K&e,r-~k Er AL-
    TAC.---z Er AL-
    sp--= rr AL.
    Er AL. -
    AND ~…~.WN +
    D=DGZ - + +
    G~>-,7-> ~^ E7 + +
    —c4z ET AL. + i
    RA~e Ax,~L -,- c 1
    Vo=
    E77 AL. 4-
    FE;?z,~ AN-- kbRZoo - -
    Ho;l>.zm Er ~L. -
    sP:~e~- Er
    BUR---(FIFLL E7 AL.
    -- *c
    PARK ¯C KIM
    O'C>;NOR E-, AL.
    L 1 E -1
    El- AL.
    FORn~O E-l
    1 E7 AL.
    E-~ AL.
    Ba;u--m< E-r AL. . 1
    ri- A.L. - -
    - S-ŠMn-, 5.16 17-13 10:13 4.B 18.15
    Pl FU AL'
    ASSXIATION WAS R-EPOR7z¯
    ASSDCZATION UIS NOT REPORTIM)
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    BATCo document for Legal Services : Health Canada 20 October 1999

    




    PAI'REN-IAL SHOKING- CONFOUNDING VARIABLES
    Ac:ESS TO MEDICAL CARE
    AGE OF MOTHER
    AIR POLLUTION
    BIRTH WEIGHT
    BREAST FEEDING
    COOKING PRACT, ICES /TYPE
    DAY CARE ATTENDANCE
    FAX:LY H:S-,CRY OF :LLNESS
    FAm.Z-,Y s--zE
    GENOER OF CH-6-D
    DE'TERMINANTS
    HEA-,ING TYPE
    HOME DAMPNESS
    F.CZ--:-iAL SPREAD OF ILLNESS
    HOUSEHOLD PETS
    NEWBORN ILLNESSES
    OVERCROWDING
    PARENTAL EDUCA-jION
    FARENTAL ZNFEC-&:ONS
    PLACE OF RESIDENCE
    SEASONAL VARIATION
    SK:N TEST REACTI-VITY (ALLERGY)
    SOCIOECONOMIC STATUS
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    BATCo document for Legal Services : Health Canada 20 October 1999

    




    A. ETS EXPOSURES
    IRRITATION, INNOYANCE
    XWE
    EYES
    TIMIT
    OTEER
    i. NO. CF IRRITANTS (ETS)
    2. PSYCEOLOGZCAL
    3. OT CI:ZER S-17,-~-C,:XNCES AYM POOR VENT,-rLATiol;
    4. EFYECTIVENESS CFF SEPAP.ArION CF SMOXERS 1M
    NON-SMOKERS
    5. SICK-BZ7::LZING
    a FOUIR B-WZLZ~NGS
    IMPROPER Y-kINTZK-,,;Cz - 30%
    ETS - 2 Tc 4% CF CO>t-PL>.IX-.S
    C. CF zl:s Y-%Y BE, AN l~;-ZZCATICN a-
    SERVES TO Y-kSX 7ZE REAL REASON FOR POOR =OOR
    QUALZZ-Y - LXCK OF P--.topz-.1
    1=74'-
    t_r
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    BATCo document for Legal Services : Health Canada 20 October 1999

    




    . "I
    THE SICK-BUILDING SYNDROME
    SICK-BUI110ING SYNDROME IS DEFINED AS A NEBULOUS
    ARRAY OF HEALTH-RELATED SYMPTOMS AND COMPLAINTS,
    E.G., HEADACHES, EYE, NOSE AND THROAT IRRITATION,
    DIZZINESS, MENTAL FATIGUE, DROWSINESS, COUGH, DRYNESS
    OF SKIN AND THROAT.
    0
    SYMPTOMS ARE GENERALLY REVERSIBLE AND NON-SPECTFTI',
    WITHOUT CLEAR CAUSE.
    DATABASE CONCLUS70NS:
    1. CDMPLAINTS ARE MOST OFTEN RELATED TO 1NADE712UATE
    VENTILATION,
    Z. SMOKING 15 DIRECTLY ASSOCIATED WITH COMPLAINITS IN
    ONLY 2 TO 5~: OF SICK BUILDINGS.
    L.rt
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    BATCo document for Legal Services : Health Canada 20 October 1999

    




    A
    IN HBI IS DATABASE OF 412 BUILDING INVZSTIGATIONS, XTS WAS
    REPORTED TO BE A SIGNIFICANT CONTRIBUTOR TO COMPLAINTS IN ONLY -3
    PERCENT OF ALL BUILDINGS INVESTIGATED.
    IN THE SICK-BUILDING DATABASE COMPILED BY TI>SA LTD.,
    SMOKING WAS IMPLICATED AS A MAJOR CONTRIBUTOR TO COMPLXINTS IN ONLY
    12 OF 408 (LZSS THAN 3 PERCE ) OF THE BUILDINGS SURVEYED.
    NIOSH 1XVESTIGATED MORE THAN 200 "SICK-BUILDINGS" THROUGH
    1984 AND REPORTED THAT TOBACCO SMOKE WAS A SOURCE OF CLAIMED
    DISCOMFORT IN ONLY 2 PERCENT OF THE BUILDINGS INVESTIGATED.
    IN A SUMMARY OF 94 (NOW: ISOO+) BUILDING STUDIES BY
    GOVERNMENT INVESTIGATORS FROM HEALTH AND WELFARE CANXDI, COY-?LA7LNT.S
    WERE ATTRIBUTIM3LE TO INDOOR CONSTITUENTS SUCH AS PHOTOCOPY MAC!r=NE
    EMISSIONS AND ETS IN ONLY 5 PERCENT OF THE BUILDINGS IN7ESTIGAT_r`D,.
    IN EACH OF THE DATABASES, INADEQUATE VZNTILATION WAS
    DETERMINED AS THE UNDERLYING SOURCE OF COMPLAINTS IN OVER RALF OF
    ALL INVZSTIGATIONS. PROHIBITION OF SMOKING WOULD NOT HAVE
    ADDRESSED THE HEALTH AND COMFORT CLAIMS IN 95-98k OF SICK
    BUILDINGS.
    f-ri
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    BATCo document for Legal Services : Health Canada 20 October 1999

    




       ITIL R L 1) lis
       CD
       P.*
       E)(?C)SU MECHA14 1~- Š?\1DISlEAsE
       ID
       ME C~t RN 1 S M
       i CL
       C)W 1 P AT A LL 1 Se E%A?O&OP.E
       CD
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       Im* (IL)
       m ECH prX %S m ?
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    In fact, cancer epidemiology has been practised
    until now mainly as a 'black-b.ox' discipline
    interested in the (presumed causal) as,sociation
    between an external exposure and the onset of a
    malignancy. Recently, however, the coupli-na of
    epidemiolog-ical desia-m with the measurement of
    biological or biochemical endpoints such as
    DNA adducts, gene mutations or chromosome
    aberrations has started to contribute to the
    unravelling of the intermediate events occurrinz
    in the chain between the two extremes of
    exposure and disease.
    0
    European Journal of Cancer 1993
    1=139 Lr,
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    BATCo document for Legal Services: Health Canada 20 October 1999

    




    DESPITE WHAT HAS BEEN LEARN-ED ABOUT THE
    ETIOLOGIC MECHAINISMS OF LUNG CANCER AT THE
    POPULATION AND MOLECULAR LEVELS, THE DETAILS OF
    THE SEQUENCE FROM INITIAL CARCINOGENIC EXPOSURE
    TO MALIGNANT CELL TRANSFORMATIO'N' REMAIN
    ELUSIVE. DETERMINTNG EXACTLY HOW CARCINOGENS
    FUNCTION AND HOW THESE A13ERRATION-S AT THE
    ~ I MOLECULAR' LEVEL HAVE . OC . CURRED WILL * BE
    IMPORTANT.
    RAY0 =:X PROC. MERUARY 19S--
    0
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    BATCo document for Legal Services: Health Canada 20 October 1999

    




    NEVERTHELESS, THE DETAILS OF HOW LUNG
    CARCINOGENS CONTRIBUTE TO FORMATION OF TUMORS
    A.MD THE ORIGINS OF MANY OF THE DESCRIBED
    MOLECULAR DEFECTS IN LUNG TUMOR CELLS REMAIN
    UNKNOWN. WHETHER THE ACTIVATION OF ONCOGE_N-ES
    DIRECTLY REFLECTS CARCINOGENIC EXPOSURE OR
    RESULTS FROM THE OVERALL PROCESS OF
    CARCINOGENESIS. IS -UNCLEAR, BUT IN EITHER CASE,
    ONCOGENES APPARENTLY ARE IMPORTANT IN
    PROMULGATING THE PROCESS.
    ,w-UC ?JIMC. r=37UARY 1993
    0
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    BATCo document for Legal Services : Health Canada 20 October 1999

    




    DESPITE DRAMATIC PROGRESS IN THE
    UNDERSTANDING OF CARCINOGENESIS;THE CRITICAL
    GENETIC EVENTS AND PROMOTION FACTORS
    REQUIRED FOR MALIGNANT TRANSFORMATION
    REMAIN UNKNOWN. WITH NUMEROUS MOLECULAR
    MARKERS IDENTIFIED, THE CRITICAL CHALLENGE IS
    TO DETERMINE WHICH MARKERS ARE RELEVANT IN
    MAPPING THE PROCESS OF CARCINOGENESIS -AND
    POTENTIALLY APPLICABLE AS DISCRIMINANTS FOR
    EARLY CANCER DETECTION OR INTERVENTION.
    0 JOURNAL OF 7~-ENAT'ONAL CANCER INS77=, SEPTEMBEr-, 1, 19C-3
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    BATCo document for Legal Services : Health Canada 20 October 1999

    




    FACTS
    100 trillion cells in body
    100 different kinds of cells
    Nucleus in Each Cell Contains 23 Pairs of Chromosomes: one
    chromosome of each pair is from each parent
    Chromosomes are Made of DNA: tightly coiled molecule
    Total DNA from cell is 2 yards long
    Genes are segments of DNA
    There are thought to be 100,000 genes for humans
    Key to Life: Genes code for, manufacture, produce proteins
    Proteins are large chemical molecules vital for existence
    Structure of DNA: Discovered 1953
    Proto-Oncoeene is gene which regulates Cell division or cell
    growth
    Oncogene is a proto-oncogene not normally acting
    Suppressor Gene is gene which suppresses/inhibits/slows down
    cell division
    loam"
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    BATCo document for Legal Services : Health Canada 20 October 1999

    




    71
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    BATCo document for Legal Services : Health Canada 20 October 1999

    




    2= 3- AC S
    tz
    . -- z_- ., .- ?; or_ V= ?QZ I =a ~ - ,
    s w - . .:~ is; I ISx I IT is
    Y;
    Two
    On =Ironxw~ 8. lis hem Me
    ~Ocxbct* &. rOO Cw=w Qwwk i*wd%ad by deft in
    t-  "I" MrV kzxmn a "Mm" (the one
    now Tw Mid04 of Vw crronlodc2m) am - Myr_
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    BATCo document for Legal Services: Health Canada 20 October 1999

    




    !igure 7-27 A i-iouble helix can be fcrme,~ by twisiing a "ladder" wiHn :9exible vcrich~s.
    sum%
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    13ATCo document for Legal Services : Health Canada 20 October 1999

    




    C
    A
    --G
    G
    -A
    -A)
    A
    T--A
    i -A
    Old New New
    S~*---nd SM-IMd Strand
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    BATCo document for Legal Services Health Canada 20 October 1999

    




    CA*CER PATHOGEXESIS
    CHANGES IN THE GENOKE I
    OF SOKATIC CELL-S
    FTICTIVATION OFJ IXACTIVATIOX OF
    0WC(%EXES ISUPPRESSOR GE.XES1
    ExPREssiox OF ALTERED
    GENE PRODUCTS AMD LOSS
    OF REGULATORY G
    MALIGNANT NEOPLASM
    0
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    110
    BATCo document for Legal Services Health Canada 20 October 1999

    




    KECMLNISSCS
    AMVAT'ZON
    - TxA.NSLDCAT10W
    - POINT KUTATION
    - AXPLIFICATION (REDUPLICATION)
    INACTIVATION
    - DELETIOk
    - IMSER-,IONS
    - POINT 14UTATIONS
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    BATCo document for Legal Services : Health Canada 20 October 1999

    




    RSLOCATION:,'
    AN
    WCKI~M
    cancer.:.:.:
    osoma 11n 0
    ReCeS. ~f Ct!
    where ~i cancer gengis in position-to gger
    tri a -. .,*---:.
    64ttL Of the genes tat make U*p*the23pairz~cf~.7..~*.'."7-**:"-,:-
    ~~ctTcrnosor~es, F?eai~y3p'can cause
    DE71ECTIVIE.
    Chroinosome'14
    7K.
    Cancer-
    jen"
    ki
    nt -
    AnU
    t7
    _7
    San= The Now MurrAn Gem= by U-S. D@MV"Wx Ct hu-sn Wd KSM S"S.'.
    r
    Crumogo TrftAw nrwds
    Th.-SWI1.136M Doom 1 9
    ~_r.
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    BATCo document for Legal Services : Health Canada 20 October 1999

    




    Secrets of a gene: cancer. wid p5,3
    S cientiZs;b~61ieye. that ciues to
    P= ire the-dgveIcpmpnt al newly aj
    type~s-cf~cAnqpr-lie in tt~e
    of cold workings:of-.the p53
    gene. A mutant-form
    . I .. w wwwy boaxly C&L UM" r 1has-been-found.in -
    am two =o" d As p53 We.
    aw Mamdacaaas awy cancersthrougho-z-,
    d I 'body, and.ft
    th e.
    a=.asmu.cther
    known-cancer
    P53 protein z
    gene does.
    By r-T-
    . I potair, t*%= tc -,-,& I ,  .
    DNA =iem=J* DNA molecule
    *thin tt-A hear e
    trA CSIL The ;~.Ieln
    "= be perlac:~V
    C=O" I it is M M I-P=-gAne:
    th.
    'L grwwas d vo DNA tTB:F=jn-n=d&trY -.28
    xCMp=w and k
    =As=rr-zrwd-ai=takw
    cn now dwgemus-U=:
    ar
    dvahm a-=Inq-0f
    and adds to-thom
    ivwcy Of the lurw.
    111100wry P= gem.
    Clbft
    TM FMMM  by Vw
    -oaW 9- habs sz;:;>(-
    3IMw polo by PI rVw a wl bnh-milg I - -
    2w - q d rww DNA . to dMdo
    0 Anded Ur cod dWff-kxL
    REE
    (-rl
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    BATCo document for Legal Services : Health Canada 20 October 1999

    




    IT HAS NOT PREVIOUSLY BEEN POSSIBLE
    TO PROVE THAT ANY PARTICULAR
    TUMOR WAS THE DIRECT RESULT OF
    EXPOSUR-E TO AN E-N-VIRON-MENTAL
    CARCINOGEN. THE LINKAGE OF
    AFLATOXI-N TO A SPECIFIC TYPE OF
    TP5-")' MUTATION RAISES THE
    POSSIBILITY THAT SOME MUTAGENS
    MAY PRODUCE GENETIC CHANGES
    THAT- ARE - - -SO - - SPECIFIC - AS TO
    CONSTITUTE A ."SMOKING GUN.11
    EREBY RAISING THE POSSIBILITY OF
    A NEW FIELD IN "ONCOLOGIC
    FORENSICS. 11
    ,WV,MCZS J.V 7R
    ..Vr!rZC C== _N
    . C.;ffCE. (1992~
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    BATCo document for Legal Services: Health Canada 20 October 1999

    




    MM%%
    QA idt b
    pp 07ej~j p~-*tb
    Er Tt C. ~ VrERPtMot4e
    L
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    BATCo document for Legal Services: Health Canada 20 October 1999

    




    ALMOST ALL CASES OF SCLC AND
    MANY CASES OF NSCLC , SHOW
    INACTIVATING POINT MUTATIONS IN
    THE R131 GENE (197). MOST CASES OF
    SCLC AND A30UT HALF OF THE CASES
    OF, NSCLC HAVE INACTIVATING POINT
    MUTATIONS OF THE TP53 GENE (19 8-200).
    IN ADDITION, MUTATIONS OF PROTO-
    ONCOGENES OCCUR IN APPROXIMATELY -
    10-15 %OF ALL LUNG CANCERS. MOST
    FREQUENTLY MUTATED IS T= KRAS
    GENE, WHICH IS ABNORMAL IN 20-30%
    OF ADENOCARCINOMAS (201~.
    AMMCES IN U?;D.=-P.ST.49DINC  --V
    . (1992)
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    BATCo document for Legal Services: Health Canada 20 October 1999

    




    mit
    W IE s &
    ON THE THRESHOLD OF UNDERSTA-NDjE~G
    If rescarch czn pinpoƒ2t
    0 risk  will it alter habits?
    ..4 the plec- irffl. CS&MOO MAI
    -%w go image . *"" ccil c~,
    lum =aba muœ il W-b‚t, te
    la pAMx%~ kidi o(
    The Ului rincii"CL. ~.0 h…- boure rrmo-ed or
    d=m a ~. M I f- ~Ib~ -dd 1
    site = te Inn lius -." t'…[ a ruocvr cet-I
    lhe dl~ la —…M le sp-d ~-AI
    te a Uoi,.c l…. .0 tm cay.
    imporru ut la~m -U.. u¯= le r"q
    -Il bc a*- U net - 1nbbca~ - 8---u- ceilLI
    Ual J's M"x. f® esr~- Im…cr Lbey h¯~
    PWIC ~ et Illb, lom te - em~=
    cm®M ", wd lait)
    1 3 se~ ci.~ l…- acte M ‚bbbg co.~.
    -m~ oetbar ena clec et ®wly
    ~b eben`t~ -9 .. abaffl Ill,
    tsrw ra.L A ~ .0- ~itt
    .'" 1 -f - l…. - …b .q -.w. (M c2…-q‚~
    ja. hŒb~V P=rfld M ®F.L
    114 MlI a" 'M  .6~ ‚coffl la auct-
    tr;
    -bel . 0- le a
    l', wc- -*,- . cala air --~fT el,
    MMIC7 Sind Mdamma. Cr ~cm~ p x 0  ffl . Iz. - . r*
    ~.e Il ~…:F Lftba the ~ bm P.Md .111` Imm
    cx--~M tjw bels, ~-C Il neccmw'Y M
    ad.- Irr ..qo a bette
    J
    .in c>,W~ IMM lez =.ut 2py' ft c
    Il Nu - -d M 10 tbe ce Wm awtzm .. - . . . ~' , - Z,
    -cle Ille &no~ lm,~ddricali te dcmm®.
    le A-, 'S. ~ = ~M the -M hua, P-
    Ltmn.
    L:
    EF&
    …
    -ji  - et~ p~ ils gr..…:jl,
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    0
    RESEARCHERS ARE WELL ON THEIR WAY TO DETERMINING THE PREC"-~SE GENETIC
    CHANGES THAT MUST OCCUR TO MAKE A NORMAL CELL CANCEROUS, AN ACHIEVEMENT THAT
    -ULAR KINDS OF
    CO-ULD MAKE IT POSSIBLE TO IDENTIFY PEOPLE SUSCEPTIBLE TO PARTI-C
    TUMORS.
    TT HAS NOW MOVED ON TO THE COMMON CANCERS, W14ERE THE ALjERATIONS ARE
    MORE DIFFICULT TO DECIPHER. AMONG THE COMMON CANCERS, THE WORK HAS PROGRESSED
    FASTEST IN STUDIES OF COLON CANCER AND LUNG CANCER, AND TO A L-75SER EXTENT
    WITH BREAST CANCER.
    0
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    ALTHOUGH A LARGE NUMBER OF FACTORS HAVE BEEN
    ASSOCIATED WITH THE DEVELDP?4f-NT OF MALIGNANT
    NEOPLASMS IN NUMANS, THE MECHANISPS INVOLVED
    ARE STILL LARGELY UNKNOWN. THE MULTISTAGE
    CINOGENESIS, PARTICULARLY THE
    MODELS OF CARC
    INITIATION - PROMGTION SCHEME, WHICH HAS BEEN
    DEMONSTRATED PRIMARILY IN ANIMAL MODELS, HAVE
    RECEI"VED THE GREATEST ATTENTICM IN THIS R-EGARD
    AND SERVE AS A CORNERSTONE DF CUiZRENT HYPOTWSES
    OF BIOLOGICAL MECHANISMS.
    JNICI, JUNE 1988
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    PERSPECTIVE: WHAT KAM A CELL RUN WILD?
    0
    . . . FOR A LONG TIME ONCOGENES WERE T14OUGHT
    TG BE THE ANSWER. NOW THAT WE UNDERSTAND THE
    IMPORTANCE OF SUPPRESSOR GENES, WE ARE IN A
    POSITION TO MAKE REAL STRIDES.
    JRCI, JAN. 2989
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    DESPITE THE PROGRESS OF MOLECULAR BIOLOGY
    TECHNIQUES FOR DIAGNOSTIC PURPOSES,
    THERAPEUTIC ADVAINCE FROM OUR U`NDERST-,A.--N-DR,;G
    OF THE UNDERLYLNG MECHANISMS SEEMS SOMEE
    DISTANCE AWAY. HOW MANY ONCOGENES OR
    SUPPRESSOR GENES ARE IMPORTANT IN TUMOUR
    DEVELOPMENT? ARE THEY STIMULATED OR DOWN-
    REGULATED TO -AN EXACT A2ND CONfPLICATED
    SEQLTENCE? ARE THESE EVENTS RESTRICTED TO
    INDIVIDUAL CELL' POPULATIONS?--- ' ARE THESE
    INDIVIDUAL CELLS ONLY SUSCEPTIBLE TO
    CARCINOGENS /TOXINS AT SPECIFIC PHASES D; TBE
    CELL CYCLE OR AT A PARTICULAR 3-0-NCTLTRE OF
    CYTODIFF R NTIATION?
    ArSPIRATORY MEDICINE, 1993
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    CANCER GENES: COIMTLEXES AND COMPLEXITIES
    THE EN2HASIS IN MOLECULAR STUDIES OF CANCER
    HAS S=TED OVER TEE PAST DECADE FROM
    IDENTIFICATION OF INNEW ONCOGENTES AND TMMOUR
    SUPPRESSORS TOWARDS UNDERSTANDING THEIR
    FUNCTIONS AND THE WAYS IN WIECH THEY
    INTERACT.
    W=ST GENE MT-TTATIONS, AMPLIFICATIONS, A.1N-D
    DELETIONS IN CANCER NO LONGER H-AVE TO BE
    VIEWED AS SO. MANY RAN_f~)OM - SPANTNERS IN- THE-
    WORKS, THE'REDUCTIONIST GOAL OF ASCRIBING A
    UNIQUE FUNCTION TO EACH ONE, SUCH TILkT 'WE
    CAN.., PREDICT THE NET EFFECT OF ANY
    COM3INATION OF GAINS AND LOSSES, RENL4JNS
    FRUSTRATINGLY DISTANT AND MAY WELL BE
    UNATTAINABLE.
    rHE LANCZ7, SEPTMOMER 25, 1993 U-1
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    HIS (FISHER'S) CLAIM THAT SMOKING AND LUNG
    CANCER ARE JOINTLY DETERMIgED GENETICALLY HAS
    REMAINED A LINGERING CHALLENGE. W14ATEVER THE
    OUTCOME OF FURTHER STUDIES, IT IS CLEAR TKAT
    THE RIDDLE OF SMOKING AND LUNG CANCER WILL
    CONTINUE TO CHALLENGE THE ING:ENUITY OF
    EPIDEMIDLDGISTS.
    0 ARCH. INT. MED., DEC. 19M
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    C002-9262
    American Journal of
    EPIDEM
    415 EDITOFdA-1
    REYEWS AND COMMENT ARY
    0
    416 When Genius Errs: R. A- Fisher and the Lung Cancer Conutiversy. Paul a ,.,Di;ey
    426 Invited Commentary: How Much Retropsychiology? J. P. Varxieribromice
    423 Authoes Response to "How Much Retropsycholcly?" Paul Z. Stolley
    !.A29 Were We Really Wrong? H. J. Eysenck
    434
    436 kwited Conirrierrtarr. Science versus Pubfic Health Action: Those Virho Were Wrong Are
    SU Wrong. SaWer Greenland
    OFJG;NAL CONTRIBUTIONS
    CT Tobac= Use and Prostate Cancer 26-Year Follow-jp of US Yeterwis. Arr: W. H37ng;.
    Joseph X McLaughlin, Zdenek Hrube-1. William J, Blot, and Joseph F. Frmo7xyr,
    442 AlcoW Consumption and Blood Pressure in Black Adults. The PM County Sludy-David S.
    Strogatz Sherman A. James, Pamela S. Haines, Patricia J. E17w. Ann M. Steven iL
    Browrw)q, Alice S. Ammerman, and Nora L: Keenan
    4si Bacteremis During Diarrhea: Incidence, Etiology, Risk Factors, and O=.-me- Marc J.
    .. -r Strue~em. Michael L Bennish, Gabriel Mondal, and Boqc~ari J. Wegynak
    lv 1 460  Environrrmntal Contamination in Child Day-Care Centem Acry Vam Arc~vje L 14cerow,
    PwAda R Reves, and La"y & Pick-irig,
    471 An Otrbreak of Cryptosporkiicsis in a Day-Care Center in Gevr9ra. &,daff ~~ 7Vv=-.-,;anr,,
    &Cp~)ef? GQrCf0T7, P3U1  and Lexie Kreec.-,W7
    T
    C17 Asses=TmTTt of Repo, th,w Cormistency in a Case-Controf Study crf Sporrtarreaus Abe-lioni'.
    Larr Fenster, Shamra H. Swan. Gay;4 C. Wincr"mm. anof Raym--:7d R. Neurm
    489 Reftbifirty of the Be,0vzvkx,&f Risk Fachm Sureey in a Trievinic population. Steve-: Shea,
    A7@h D. Stern, Pafi* Lai*gm and Charles E. Sesch
    501 CharxXs in Conwri"Ied Body Mass Index Dist7tititioris Associefed with Se=lar Trends
    in Oyrrweighl among Danish Ymbg Mem R Ar*n Pme. Aoberrs Ness. sne 7horkiid 1. A-
    Sorensen .,j; Q/
    Conbraped an hside F=-Caver
    T- Y-`
    EWE if-
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    L BATCo document for Legal Services : Health Canada 20 October 1999

    




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