Tobacco Documents Online

1~l1~/ _.ot~eiil~lf_'F' 11, ll 'i MEPIORANDL'M - TO: W. T. -ilcr~ t CC : I11i1t WUG FROM: Leonard S. Zahn RCH -kiC SUBJECT: First International Congress of-Twin Studies, Rome, Oct. 28-Nov. 2, 1974 Attendance at -this Congress was so:newlzat- small, varying daily between 40 and 80 and seeming to shrink with each suc- ceeding day. A?any of the attcndees were young staff members of the host-Mendel Institute. Of course, few scientists are engaged in twin research. Lountries with the largest number of representatives were the U.S. and Sweden. - At_least four papers were given on twin-research going on in the U. S. All dealt with the same population, which is described below. Clearly, very little effort-had beeii--mY3de to attract - press coverage. Joann Rodger s of the Hearst newsp<<pers learned of the meetir.g from me while in Florence and came for two days. An Associated Press -corresp onfaellt sI''_ol:'ed l.lp- brleil,', as did reporters for one or two-RRome dailies. I souglit to int~_-;rest tl.e press in interviewing-Cederlof (after first getting his approval) . Rodgers saict -she had -al- ready done her tobacco story for tile trip (the Horn inter- view in-Florence). However, a reporter for Il Messa.--gero tallced with Cederlof and some of his associates from the Karolinska tastitute and wrote a storv in the Oct. 30 issue that read partly (and roughly) as folloe:°s : SWEDISII SCIENTISTS AT THE CONGRESS ON TWINS IN ROME Smoking is not too "greatly" reslionsible-for cancer. Studies investigating tsvins, smokers and nonsmokers. by Luc iano Ra gno Smoking-is responsible for tu:uors. That is certain. That is already known. I3sit its significance on tl:e formatlon of the terrible disease is possibly not so excessive as recent studies have maintained. This was ascertained by Swedish scientists -- the results j_jnnounced yesterday in Rome at the First World Congress on Twins -- who had studied groups of monozygotic twins. Other factors intervene in- formation of tumors. WhicIi? They had not been investigated, eonard al4n vUN'iC RfIATiUNS C0U~13EL nndAssociatalnr- P. 0. BOX 523 • 13 LINCOLN ROAD • GREAT NECK. N.Y. 11021 •(212) 895-7545

answered the Swedes to that niiestion. Wltat is certain, however-, is that there are factors inherent in each - single lndlvi;iu.zi. This -is an important statemetit. It does not - reh.lbi1 itate _ smoking but _plac es it in the (lock to;_ether_ with others accused, in company with other factors re- sponsibLe (for the disease). This situation was made pos- sible through studies of twins, an ideal medium for in- vestigating phenomena in several persons as if they were one. - -0- 1. U.S. Twin Studies -We'll be hearing and reading more in-the future about twin research being supported by the National ,-Ieart and Lung ln- stitute. All are using the sanie subject-population: The-tiational Academy of Sciences-National Research Council has a twin registry of-iaale veterans born_in the contiguous U.S.-between 19-17 and 1927. 'They serv-ed-in the armed forces either in Wor-ld=Br'ur II or the Kor-ean= War and were between 42 and 56when examined as part of the \'HLI twin study. The NAS- NRC NRC registry contains more than 16,000 pairs of such twins of whom about 7,000 responded to initial mail -questionnairee in the early 1960's. Invitations were'sent to 1U93-twin-pairs and, for various reasons, the-study population ended up as total of 514- twin sets. -TY:e-ir zygosity- was -determined by extensive tests that confirmed the-twins' opinions of their zygositti° in almost every case. The total includes 250 MZ and 2b4 DZ twin pairs. The twins were drawn from three geographical areas in-the U.S-. and were examined at five-examination cent-ers, selected so that no twin°had to travel more-tha_n 200-miles to_be examined. The examinations, using forms modeled after-those used--in the Framingham lieart Study, included a-detailed family,-medical, twin, and dietary history. Studies based on these twins--and reported at the Rome meeting included: "Genetic variance in_°b1oQd pr-essur=e," by N. Borhani; "Genetics of plasma cholesterol and triel.vicerides: a study of male adult twins," by J.-Christian, and °1Her-itabilitv of personality and behavtior patterns and their correlations with risk factors for cor=onary heart disease, " by Ray Roseiiman, - The last=nafned covered- 190 twin pairs (93 MZ, 97 DZ) re- siding-i-n California. All the data presented in-tlipse studies appeared-to be preliminary.- 2. "The cotwin method and experimental science" -- Rune Cederlof, Stockholm. This was mostly a review- in-which Cederlof

emphasized_ the unique value oi_ twins in- experimetttal- research. lie point.e<I or:i r1oti.£ iinl~c>r•t_arit_ Lw ii- re~e~ir c11 i;as_ in evalztatirt~ the effectt of ertviron!ne.n+r,l eYPosLrres =such-as air po;-Luti<,tr-, : r~al. irr_, et.c. O:i- t;t(,_ (-)t.lier -;„-tnci-, a pro:bl-er-ii is the dil f icult{ ir_ compi c'itoU:;ti tw_in 5arspies to wai•1°ant -s-our-rd sta- tistical conclujs.ions._ However, the constituti-onal• _hy_PntheSis c.-rltnot eas i-1. , if at all, be -evaluated- on any basis other than_ twin research. Most o_f_ the lar-ge epidemiological studies on- - smokin,g that have been reported are of the ex post facto type. Cederlof slio,ved some slides_ from a paper scheduled to-have been given at the twin session by a colleague, Per Caritner, who was unable to atten_d. Camner's work crovered-tracheobronchial clearanre in 2,,17 arrd DZ twins exposed to environmental agents. Clearance patterns within 9 pairs of rIZ twins-were striking- ly similar but not within 9 pairs_of DZ twins._This indicates that clearance patterns are to a great extent genetical' y de- t-ermined,-according to Camner. In, 10 pair-s _of smoking-discordant rliZ twins, cl-earance- was on the'-average slowe-r in the-smokers. In another study,-15 MZ pairs were examined, one in each pair having lived in Stock- _ holm for the last 10 years and the partner having lived in a rural anea- or a small tow:r during the _ same period. No signi- ficant differences in clearance patter;r.s within-the pair-s_couid be seen. - Nasal mucus flow tivas-also measured in 12 pairs of MZ twins. An almost-si;Jnifi.cant correlation of the flow rate was found between the members of each pair, suggesting that genetic fac- tors are at least partly responsible for tae large_dirferences in mucociliary transport in the nose-. 3. rrIschenic heart-disease in death discordant twins" -- Ulf de Faire, StacklYolrn. Subjects consisted of 205 male arid female tsvin pairs from the Swedish registry. During the 1971- 73 period, one of the merubers in an unbroken pair died and surviving cotwins- were examined on average five months after the death of the partner. Results showed significantly more clini-cal-and subclinical signs of I11D among surviving cotwins whose partners hfid died_ from ItID -compare« to those whose -par tners ci_i_ed from causes other than_IIID. This difference was especially pronounced when D1Z twins were compared. Findings indicate a- substantial gerietic influence in the development of 111D-and, furthermore, the genetic influertce seems to be transmitted not only through some of the risk factors measured but also through factors which are still rtnknotirrt. (Risk factors- measured itr- cluded anthropometric variables, blood pressure, li.pids, uric acid.) -0-

De Faire gavee me a leiz,_thv document that 'is being issue:d as a supplement to Acta Medica Scandinavica and is-a fuli r'e° -port on l1-is --5tud ;_ of' the 2C f twin pairs._ In regard to `tol)acco, he notes: With regard to__smoking, aicohol, physical inactivaty and some social factors, no substantiai_differences were_found be- tween the deceased - and -the survivin_g- twins. ';'he If1D death dis- cordant pairs included a somewhat-higher proportion of total smokers as-weil -_as--cigarette smokers, compared to _tlrie not--Z1aD death discordant-_pairs, and the-proportion of cigarette smokers was especially high among the male IIID death discordant rIZ --- pairs (6C'% amon- the-d-eceased-_partners and 80% among the- sur- vivors). Ivlost-epiciemiological studies point to a_positive relation, especially in_ men, - between- IHD mor-tality and- smoking. No as- sociation was found in the present study but it mus-t be born = in mind that the numbers involved are small. The surviving rIZ and XZ (unknown zygosity) male cotwins-whose partners-died from - of more than 11-ci-garettes daily) IIID were cigarette_smokers I proportionally more_ ofter.- than_ the other male_ MZ and XZ twins, a circumstarice which r,:ay-have contributed_ta tl:e_correspond- -ing differences in-IHD manifestations. Hoii-ever,_ the deceased r1Z and XZ twins also showed ti.e same tendencies- ii. ~he smoking of cigarettes. Thus it is possibl-- that the differences with regard to smoking merely reflPe.t dif ferences in constitution, which could play the major part also_with regard to the de- velopment of IIID. 4. "Coronary heart disease in male twins" -- Ingvar Lil- jefors, Stockholm. In-__1967 a sample of 91 male twin pairs from the Swedish registry was examined clinically for the presence of overt CHD -- 19 rIZ and 18 DZ were found to be discordant with respect to presence of IIID. ihe examinatior. included physical work-up, cholesterol measurements and habits-such as smoking-. All but one of_the-37 pairs were followed-up in 1974 with these findings: 18 were still healthy, three of the partners had died of mvocardial infarction, seven had developed angina pectoris, two NLIZ partners had died from other causes, arid six had uncharacteristic chest painrs or other vague symptoms. - In a comparison of the ti,;-o groups of-twins with and with- ou± symptoms of overt Clii?, no differences were found with re- spect to blood pr, e_ssure, serum-cholesterol or smoking liabits. It was concluded that none of these factors appeared to in- fluence the future de_ve.Lopnient of CIiU in twiiis who seem to be genetically-predisposed for this_disease. 5. "Twin studies in relation to the mechanisms of age- dependent disease" -- I'.R.J. Burch, Leeds, England. l!e pro- posed what lie called a"unified" theory of the etiology and

pathoRenes.i5 of di5ecz~ses -1yitii a repro.[lici.l,ie a,e-<li-sLi'il)1ttion. His d.heorv -- complete _with some complicated mathematical for- mulas -- i.% -basec.i -o:i -tlse claiin tfia-t eacii iJeLl-clef.itted age-de- peiidenL disease is initiated t:y a characteri.stic set of rarzdom gene mutati.ons in stem cells of the central system of -gro:.th- control. it applies to-ma-litnant, non-malignant and infectious diseases and was derived after- study of several hundred- age patterns--- or age-specific on_ets----that arise in connectior: with certain human diseases: lie has dev-eloped a biolo-gical= stochastic model-which, lze-says, also takes into account the latency period of diseases. Burch also spoke of the rclevance of twin studies in de-- terminin- the constitutional or environmental-causal hypo- thesis of disease, particularly when such habits as smokiaig or drinking are associated with a disease process. Referring to Friberg and Cederlof, he said the data strongly sunport_- the theory that any relationship betwoen smoking and overall :::or- tality seems to- be constitutional, though- the numbers- studie=d are srr:a-I1 e Commenting gfter Cederlof s~oke-, -Hurch said he agreed -that the cotwin- method promises to provide the best- test in regard to environmental causalitv or constitutionality. He emphasized that conclus-ior.s'-from twin studies- sl_ould be consistent with evidence obtained by other research techniques. As an example, he mentioned the secular chan-es in connectioii_ with Gmokine-. noting that lung cancer had been under-diaynosed at the be- ginning of the century and was being over-diagnosed now. 6. "Alcohol consumption-in relation to variables asso- ciated with ischemic heart disease" -- Marten Myrhed (he was absent-and his-paper was read by a colleague). Seventy al- cohol-discordant male twin pairs aged 1f5-65 were studied. The high alcohol-group had higher blood pressures, smoked more cigarettes, coughed mcrre, had more asthma, phlegm and dyspnea, and-also dispiaved other measurements hi-gherr than those-seen in the low alcohol group. The importance of these variables for development of I1{D in groups where the constitutional fac- tors are kept under control is not known. - 7. It's interesting to note that several of the papers from tlie Swedisi: group -- especially those dealing ti,ith heart disease -- are the direct result of suggestions made at the 1969 twin symposium in Piterto Rico-. r\ri imt ortant aspect of the research of the S;;edisii Twin Remistrv is a continuous mortality follow-up of all the twins. Since January 1971, - information on deceased twins has been available every month, thereby permitting clinical examination of the-survi.ving partners within a reasonable period of time. - It's expected - the procedure can be applied not only to I1.D_ but to other chronic diseases-as well.

. 8. At the close of the Twin Congress, a_ proposal was made -- f-oT' better, more r:ete?`isire 1.1terri_at1fl21E1i cooF)eratlon-._ The Mendel Institute in Roine is- now ;ettinZ cluta from the N'AS-\iRC twin registry in the U.S. -A PHS scientist,- 2denelc _lirubec, is -sgenC- ing a year at trie Karelinslca I nstitute in S_tockllolm. l

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