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P.O. Box 2370, Reston, Virginia 22090 Teiephone 703-6204646 DCE BOARD APPROVES CONCEPT FOR NEW $850,000 YEAR GRANT PROGRAM TO STUDY VIRUSES IN CERVICAL CANCER ~ A new grant si.spported research progra m to in vestigate the role of ~ papillomavintses in the etiology of human cervical cancer, with annual i funding estimated at $850,000 a year, was given concept approval by Fn Brtej (Cadinued to page 2) I FY 1985 BUDGET BREAKDOWN: CONTR'OL GETS $64 ~ MILLION, CONSTRUCTION $6.5; W.VA. $4.5 MAYBE BBRH'tt BO'N the three major questions left unclear in the appropriations bill Congress approved for NCI probably wiil be answered: 7Tiere Will be $6.5 million for eonstruction, rather than the $13.5 million asked by the Senate. Up to $4.5 million of that will be available for WP.st Virginia Univ., but whether any or all of it goes I to W,Va. depends on peer review. Any that does not go there will be availaable forother construction grants. Cancer control will get $64 million, up only $1 million over PY 1984. Research training (NRSA) will get $31 million, which will permit paying higher stipends.... ' C33NMRS ARE 'pot well thought of at NIB and "are considered the ~ f'u-st area to go when buc>gets are eut " I8 CI Director Vincent DeVita ~ sa'id at the Preside'nt's Cancer Panel meeting in Seattle. "('crs ttrs are ~ always at risk. Zfiis is very distressing to us.. . OM B hr.s resolutely !r«^.d-c°.^.dt.12e.*e iS :I^ w F., tl:°1, ~ will (change) unless Congre3s and people who feel that we have to ~ rebuild ourlabofiatories get the message across...I am very, very i impressed that the amount of money we have pput in construrtion in centers has uvially been a quarter to a third of the monies requ:red. i When you look at the money that was brought in to build, t,wse buildings, it was not money that normally would have come to that institution without the seed money from government. I think these ~ facts a,re not well reeeived in OMB. We like to pick on 0 M B. I thtnk we are allowed to pick on OMB, as a matter of fact",...TAIO BRANCH chief appointments were aruiausced by Div. of Canoe Etiology Director Richard Adamson: David Longfellow, who has been acting chief of the extramura] Chem ical & hhy9cal Carcinogetes3s Branch, has been named permanent chief of that brench. Peter Howley has been named chief of the Ieboratory of 'IU mor Vuvs Biology.... DIV.OF CANCER Prevention & Cflntrolisrecruiting for another branch chief, the Diet A Caneer Branch. It is a Civil Gervice position at the GM-15 level, with a salary range from $53,407 to $66,400, with physicians eligible for eomparabiiity pay of up to 510,000 more. Candidates must meet the requirements for medical officer, with experience in nutritional science, epidemiology or related fields. Contact Janet Gregory or Jerry Chambers, HCI Pemwonnel Office, 301-49"852, lflCoDJrrght 1984 The Cancer Letter Inc SvDSrr.^+ror, $150 veat Nonh Amer.cy $1 75 vear eliewhere DCE Publishes List Of Resources Available To Scientific Community ...Page7 R FPs Available, Ciintract Awards ...Pa$e8

lii;:...'' I CEF:VICAL CANCER-VIFlUS STUDY WOULD SUPPORT EIGHT GRANTS, FIVE YEARS (Continued from a e 1) p g the BoarcDof Scientific Cothnsebors of NCI's Div. of Cancer Etiology at the Board's recent meeting. The Board also approved the concepts of new contract supported initiatives with estimated annual costs totaling $ 2.2 million and of the recompetition of existing contracts with estimated annual costs totaling $4.2 million. 7be papi7loma%irtts cervical cancer study would fund as many as eight grants for five years, DCE DirectaRiehard Adamson ssid.'d4te concept came out of a workshop held earlier this year, chaired by Marcel Billuda,a member of the DCE Board. Staff description of the proposal follows: "7tie consersus of the workshop participants was that the human papillomnvirtues (HPV) were the strongest viral candidates for a m,ejorrole in the etiology of cervit..al carcinoma. Several laboratories have demortstrated the presence of HPV DNA in both e:ervical ca.rcinom as ®nd dysplasias. In one study, 70-M per c~et[t of cervical tumors contained DNA from either HPV types 16 or 18. In addition, mild dysplasia, appeared to be associated with the pirqertc~of DN A from HPV types 6 or 11. A nu mber of establisned cervical tumor cell lines have been yeatmined and found to possPss DNA segments of HPV type 18. ijPV antigens and cytologicaD markers have also been detected in a large percentage of dyspla- sias examined.Other HPV types have been strongly associated with human laryngeal papillomas and the skin disease epidermodvsplasia verrueiformis. Variotsaraimal papillom aviruses are also known to trartsforr.t eeils in culture and to induee malignan- cies in their native hosts. "7tte woiirshop participants noted, however, that little information was available on the expression and function of the HPV DNA found in the dysplasias and earciriomas and on the progression of thn disease (rom primary infection to dysplasia or carcinoma. Studies arw needed to determ ine the natural prog- ression and transmission of HPV infections (e,g. rbes HPV infection always precede the development of dysplasia and/or carcinoma?); the expression and function of the associated HPV genome at various stages in the pathogenesis of cervical lesions; and the host response to such infectiorts.'fiese ques- tions have not been answered due to a lack of basic information on the mechsnista s of virus replicat ion and oneogenie transformation. SLitable rell culture systems have not yet been found which could serve as models for these functions. However, the avnila- bilityofrFcombinant DNA techniques should help overcome this impediment.'Ihus, it was eonsensus of the workshop e artieipan:s that studies in ail the above areas are needed. Such studies will help to elucidate the role of HPVs in the etiology of cervical cartcer. "The major emphasis of the basic research to be ftarded ttnder this RFA wi71 be sWeson the molecu- lar biology of HPVs and on the natural progression of HPV infection in its native host. Examples of such studies (which are not all encompassing) are (1) elucidation of the mechanisms of viral infection, replication and anecigenic trwsformation; (2: developlment of in vitro model systems using either we7dtypeorgenetfcaIlyengineered HPVs; (3) funetionalandsttuctural characterization of HPV encoded proteins with particular regard to patho- genicity and tissue specificity; (4) determination of the HPV types aseoe.hated with specific categories of cervical lesions; (5) determination of the rates of regression or progression of cervical lesions in HPV infected subjects (these studies will not preclude the referral of human subjects for treat- ment when indcated by accepted medical criteria; (6) the nature of the host's response to HPV; and (7) the role of other viral agents, such as HSV or CM V, in the oncogenic process " Alan Schreier is the program director. Another major new initiative was reflected in the Board's approval of the concept for a contract, to cost nearly $1 million a year, for support services for biochemical epidemiology.It will be competed as a prime contract, with subcontracts to be awarded for individual projects. Descriptions of new oontract concepts approved, with staff justifica- tions, follows: Tatle: Btiiologic in.•estisatiaass of raue reprodt.c- tive eancers. Estimatcd first year cost,;300,000, two years. 7he Enviror.mental Epidemiology Branch has an established program of research on a variety of eancers of thc reproductive system and the breast. Studies are aimed at cancers that a:rc rclatively eom mon as well as those that arc lts% frequent. Among cancers of the reproductive system that ha ve reeeivedl+;mited epidemiologic sr• on are malig- nancies of the vulva and va .. Both are rare eaacers, the average amtual a ge adjust ed inciden c e pa 100,000 women in the SEER areas in 1973-77 being 1.6 and 0.7 for cancers of the vulva and vagina, respectively, Both cancers are more common in older tvomen as well asin blacks. Apart from these features lit tlt is kAown regarding the etiology of either Jiscase. Varioua risk factors have been suggested, but for the most part are based on clinical case series rather than carefully designed ease control investigations. Among the postulat ed, although not establisbed, risk factors for vulvar carcinoma are low soeioeconomic status,obesity, vitamin A and E deficiencies, early age at meno- pause, smoking, hypertension, diabetes mellatus, tnfec tron and/or traum a relatrd to poor personal The Gst9cer Letter Page 2 / Nov. 9, i984

bygicue, promiscuity, and piemalignant vulvar lesions. For vagrnal eancers, the role of trans- placental estxogenghas been wdldocumented among young womkn with clear cejl adcnocarcinoma. Among older women, who habe mainly squamous cell trumors, some attention has been given to vaginal trauma, including pessaries or rn'urics at childbirth.Or.her unconfirmed factors are chronic l,eukoxthea, leukoplakia chronic vaginitis, late menopause, obesity anJ douching practices. Ofreceatintereatas arcportedincreaseinthe incidence of iz situ vulvar lesions, particularly among youager women.This paralkla changes in eexwlbchavior,leading to speculation that vulvar tancer,li.ire cervical ea.ncer, may be caused by a $cnrall~•~ ~t`ra~nsmitted agent. Herpess3mple:virus tppe ?(HSV 2)haa been identified in vulvar tumor fissue and many cases show serological evidence of priorl~erpe.ainfection,Htunan papillomavirus (HPV) fls known to cause genital warda (condyloma acuminatum) which have been followed by vulvar cancer in a substantial proportion of cases. Furthermore,insituvulvar cascinomas have recent- lybech found to contain HPV antigens. For vaginal cance¢s,noepidemiologie or laboratory investiga- friansliave been carrred out to evaluate the role of anfectrious I ' agents. It haa been suggested that diff erent squamous eancers of the lower reproductive syst c m m a y ha ve komrnon edologic fae tots, particularly in vre w of emilar demographic patterns (e.g. high rates in ack women) and a tendency for multiple primary tumors involving these sites. For example, vaginal carcinomas are often diagnosed simul- ttneotrsly with carcinom as of the vulva and cervix, as well as frequent:y a few years after hysterectomy for severe dysplasia or carcinom a in artu of the cervit.'lhes'e observations have led to a theory of the mluu'.aAanc uujyCai Gf wp:;: .= L^ll CarrT..nm p a of the vagina, vulva, and cervix. 7bus, epit6elial maligktannes of these sites may arise in response to the same etiologic factors; the older age range over which vulvat and vagin al cucinom as usually appe a r compared to cervical cancers may be due to the longer latency periods for these two sites, or to the action of cofactors or promotional agents. Since solitt1eiaknownaboutthe causes and mcchanisma of eitber cancets of the vulva or vagina, thcre is a needforwe$idesigned case eontrolinvestigatians involving reladvely large geographic areas and/or longtime periods to accrue sufficient numbers of cases for study. The objectives of tbis contraet, which will combine research and support activities, are: (1) to idcntif y environm ental exposures of women that przdict the risk of developtnq %•ttlvar and vaginal cancers; !z) to relate serologtcal indicators (e.g. infectious agents, mieronutrients) to risk of thes0 cancers. Idially, this case control study would be popu- lation based in which easts represent all women over sgc 25 yeaxs with in situ and invasive vulvar and vaginal cantersina defined geographic region and controls a sample of the genertl populationof the same geographic area. If this design is not feasible based on RFP responses, the study r,ill be hospital baced with eases representing all vulvar and vaginal cancer cases diagnosed witttin a defynkd tin; e pe riod. In this circumstance, controls would be either hos&alortaeighborhoad controls,detutnined by the referral patterns of eligible cases. It is antrcr- pated that study subjects will be accumultted from seaeral cancer registries or clinical centers, and thmt approrimately 400 cases of vulwar cancer and 175 cases of vaginal cancer diagnosed ovct a two yeai period will be included. Approximatcly 800 control subjects will be selected in such a manner that tluy can serve as a common comparison group for botlt cancer sites. Both c ases and cantrols parcrci- pating in the study will be intcrvie®'ved using stan- datdized data collection forms develcpsd by N CL In conjtmction with the interview, a small sample of blood will be requested from all study subje,c ts for deAermination of serum antibody and mtsronurrient lewels. It is anticipated that assays for ccrpes simplex virus types l and 2 serum carotene/retinol and tocopherol will be coahtctedtmdkrvapp ott f rom a separate contract. Additional aera will be f roren for future deternination of papillomavirus anti- btttlies,lnaddition once the collaborating centers have been eatablished, the logistics of obtaining fresh ttrmor specifxens on a sample of cases will be asatsaed.'Ihis subsample of the total casc series will be used to assess the frequency of papillo- mivirus infection. Standard methodsfor analyzmg caae contcol data will be emploped.'Ibcse will include estichate of risks associated with various exposu; cs. Sinc e m any of the factors will be highly cortelated, multi- variate analyaaa will be pursued to define indepen- dent effects. Louise Brinton is the project officer. '1111._i _. c'oae contrnl atudv of cancer and drialdng ws+ter eontamiaiactts. Eatimated first year cost. $150,000, three y.-ars. (NCI will contribute a.n estimated $980,000 total to the project, EPA 17Q,000). In 1975, chloroform and otht:r halogenatzd o-ganics were discovered in chlorinc treated drink- ing water. Toxicologic and epidemiologic studies were mounted to evaluate possible risk to hum ans. Elevatedtmmbers of kidney and liver tumors were observedin rodent feeding studies of chlo,toform. Epidemiologic surveys showed geographic correla- tions between site apecifie cancer mortality rates in U.S. counties and drinking water source and treatment. Case control studics usnng information frotn death terr.ific ates confirm ed and extended these observations.'Ihe most consistent positive (indings were for c ancers of the bladde r, eolon, r e c tb m, and brain. Pancreas, stomach, andlung cancers were also cotrelated with drinking watet source, but leas consistentls. Usingdata from a large case control interview stvdy of bladd er c anc er, and inf or m ation f rom an independent survey of water utilities, we have developcd a n_ethodology to czplore assotiations between cancer risk and drinking water source. WFule there was no overall risk elevation among persons The Cancer Letter Vol. 10No. c3 / Pag,• 3

i1h:.._ , using chlorinated durface water for long periods, selected findings from this study do wartsnt further evaluation. Among stttdy subjects otherwise at low risk--nonsmokets who were never employed in a hij&h risk occupation-bladda c anc cr risk inc r e ased wttb duration serwed by chlorinated surface water sourcca.In the study area with the most intense agriculttual Iand use, bladder c ane er risk am ong all risk groups increased with exposure duration to chlorinated surfaee water sources. Objectives off this study and its contract are: ].Todetermibe the risk of incident cancers of the colon, rectum, bladder, brain, and pancress associated with asnurce of drinking water. Liver and kidney cancers will also be included, if feasible. 2. To replicate and refine observatiotasfron, the National Bladder Cancer Study of associations, in an agrikultural statcMbctween bladder cancer risk and the use of a chlorinated surface source of water, 3. To evaluate the effects on cancer incidencs of duration and latency of water related esposures, as welll as the interaction of these exposures with other site specific risk factors, such as cigarette smoking and usual occupation. 4. To improve and refine modds used to est im a t e past exposure to czreinogen4 in drinking wa t e r. Tbe Environmental Protection Agency will collaborate with NCI in thib part of the study. A population based case control study using mailed questionnayres is planned of incident c anc e ts of the colon, rectum, bladder, brain, and pancreas that occur within a defined geographic area with an existing population based tumor registry.The time period of diagnosis for eligibility will vary by cancer site to ensure adequate numbers and statisticalpowu for cachsitc.'IToe geographic area will be sdected to limit the ascertainment period for anyone cancer totwoyears.The area must also have telatively low inmigration, and must have a varicty of drinking water sources, including con- iaminacion i:cc gcounu waicc auu 3uaiaCc avwiCcS likely to have beett contaminated with high levels of chlorination bpproducts, pesticides, nitrates, and otherpatcnriaUytozic compounds. Cases wiLl total approrimately 2,500 with 300-600 for each anatomic sste,Fifteenh:udre(f controls will be selected from the geaeral population, frequency matched to the espectedproportion of cases in strata specific for sex, race, and age. Controls less than 65 years of age will be srlected by random methods and those 65 and oldetfrom a random sample drawn from Health Care Financing Administration rosters. D;ta from residential histories will be merged at NCl with histoiieal information on water quality to establish a ltfetime e:pasure profile for each respondent. Standard methods for analysis of unmatched case control data will be used to evaluat e risk for each site specific m alignancy at related to drinking water qua1ty. Risk will be evaluated fot 14 vel, duration and latency of exposure as well as interaction withothet risk factors. Water quality will be estimatedby applyogbistorical inform ation about aatcr supplies to statistical models that are based on recent measures of chlorination byptoduc ts and othei contaminants. The coattact will be a Thte Cancer L.e7ctei- Page 4 1 Nov. 9, 1984 teseatcb contract because of the need for a princi- paliqvestigator who has experience in conducting epidemiologic sttrdies, whobas access to a popula- tton based tumor registry, and whn is knowledgeable about water systems in the region. The EPA Wealth Effects Research Labotatory in Cincirmati) wiIl coalaborate with N CI in estimating past esp9atttes. CturentleveL of tnlulOmetbanesin drin~king water supplies of the study area will be meaaued several times and compared with each other and withlevela meeaured five years ago. Ccwsistency of rtnkorda amorig suppvies will',alstcr confidence in extrapolating to htstorical levels for these cosrta minants. In addition, five represent ativ e wat e r supplies will be studied intensively to determine the feasibilit of estimating historical drinking warcr levels ofypesticides and nittates. Success in this effort willpertnit epidemiologic evaluation of thest contaminants. EPA has agteed to contribute #yn nnn rehtlp defray expenses of environmental meaaurements,'Ihe EPApro'eet offica w~11 oversee environmental aapccts of this project. Kwmeth Cantog sa the N CI prolect officer, and Gunther Craun is the EPA project officer. TStie: Support services for biocheani¢al epmdemi- ology. Estimated first year coat, $940,488, four years. In recent years there has been growiag enthusiasm for incorporating the collection of biological apecimuss an3 the performance of laborptory studies into the design of epidemiological studies of cancer,These include studies of (a) viral serology amd vital rnuldc acid sequenc es in patients with or at risk of bepatoeellular carcinoma, Burkitt's ly_mphomaraasophar~agcal carcinoma and carcawma of tbe uterme cerv4:; (b) hormones in breast and proatatic cancer; Cc) micronutrients in cancers of the )uug,larynz and urinary bladder; (d) carcinogen DNA adductsinpexsotts exposed to environmental Yrbuaoitti;, iYM :wav'w~.:f o s' C w: L: LA.3.. C w~ (e) bile acids steroids and mutagens in colon cancer.7lu Qemiology 8 Biostatistics Program ard the Labocatoeyof Human Caranogenesis p..HQ of N CI have a long standing interest in and involvement with this emerging new discipline, biochemical epidemiology, by virtue of its program of inter- disciplinary studies in persons at high risk of cancer. In this context, the staff of the Envirotunental Epidemiology Braneh (ESB), Clinieal Epidemiology Branch (CEB) and LHCbas accrued considerable expekience in collecting processing and storing biological specimens, aMn applying viroiogic, cytogenetic, immunologic, ina munogeneac, molecular and cellular sensitivity assays to the materials collected, in collaboration with appropriate laboratory scientists. Observationa resulting from this workinclude: (a) eharactetiza- tion of the relationships betwe en hu m an T-ly mpho- tropic virus (HTLd»1) and adult T-cell lymphoma (ATL), HTLV-3, hepatitis B virus, and acquircd immtrre defidmcy spndrome (AM8); (b) demonstutton that helper isuppr e ssor cell ratios and acid labile alphaintetfeton ate usefulsvrtogate markers for AI)S risk; (c) the finding of henzo(a)pyrene DN A

adducts and anttbodies to these adducts in persons exposed to this compound in the workplace and via t bacco smoke; (d) documentation of important relationships between the major histocompatibiLity complex (HLA) and familial susceptibility to Hodgkin's disease, hairy ce111eukemia, and Walden- strom's maceoglobulinemia and to infection with HTLV-l; (e) identification of abnormalities in cellular response to c arcioogens in f affiilies prone to sarcomas and to melanoma; and (0 description of a 3:8 chromosomal cranalocation in familial renal cell carcinoma.More recently, this approachbas beenappliedbyotherinvesuigators in the Epidemi- ology & Biostanatica Program. Current projects of this type include: (a) an assessment of serum micro- nutrients in a case control study of women with cervicalcancer- ~)tbyroidl'aormone measurements in a cohort o~ childten irradiated for tonsillar bypertrophy; (c) quantification of eytogenetic abnormalities in vanoua uradiat ed populations; and (d) a hepatitis B serosurve,y in a study of pr~imary liver cancer among World WarIIveterans..e.dditional opportunities to incorporate a biochemical and/or molecular component into emiologi'c investiga- tions are widespread, an appear to offer~great promisebotb as measures of cancer susceptibility and aa indicators of cardnogeA ezp osure. However our ability to undertake such studies is 'constraineJ by the available resources, a lack of flexibility in erpeditiously marshalling resources to test new etiologic hypotheses and lack of a systematic mechanism for obtaining the required services. In the past,program ataf f have had to locate approp- riate resources for a particular study on an adyoc basis, and once identified, initiate individual contract procurement processes that were oftet: subject to delay and, whed totalled, excessively coatly.The availabilitp of a single procurement meehaniam through which efficient access to a wide range of high quality laboratory assays could be obtained would pcrmit additional program initiatives in these areas.It would also provide for st andard- iration of operation,inue as ed qualit y cont rol, and improved management and supervision. EEB atd LHC propose toiprocute support servic es for projects in biochemical epidemiology. We cnvinonselecting a contractor with the following capabilities: (a) experience in the collection, sbtpment, processing and $bort term atorage of a wide veriety of biological specimens Gncluding whcle blood, serum, plssm a, r ed c ells, whit e c ells, urine, feczs and tumor tissue); (b) e:perience in the performance of laboratory work; !c) experience in monitoring and computerizing the accrual of laboratory data particularly with reference to appropriate use 01 quality control procedures; and (d) an ertatsive subcontracting capability, by means of which a broad range of sero:ogic, hem atologic, bacteriologic, vhologic, molecular, enzymatic, micronuuient and exposure related assays can be puschased.'Jtte final requirement is needed since the wide range anddiversitp of assays required makes it unlikely for any oee laborator to provide high quality laboratory suppr.rt for *.Ll the tests required.'lhe responsibility for col)ecting epide- i, '(-. . . .".'7 miologic (interview) data would not belong to the proposed contractor. Tbis would be handled through other program reaources. As a resource contract, the laborator~yoasay~~ sought would be only those which are available on a servic e basis. No develop- mental work would be procured with this med:'anism. While it is e~ected that the contractor will have some capability to send specimea collectors into the field, under most tiscudnstancea the cost of specim en collection will be built into the budget of each specific study.7hus brdinarilP, the contractor's responsibiliues would begin with the logistics of specimen transfer fgom the field to a central processing and short kerm storage facility. Long term specimen storage would be handled under an existing contractrthrorighwlnchEEB already main- tains a eomputerized biospecimen repository. The management of this contract will be shared betwe en EIiB and LHC. EEB and LHC will each provide a coproject officer to oversee the procurement. Proposala to incorporate a biochemical component into newly planded epidemiologic studies will be , reviewed by, and requireapproval froml a su member committee eomp~.ed of thrce senior investigators from each brsnch.'TUia panel will be supplemented on an ad hoc basis by N CI s eientists with appropri at e specialized area3 of etpertise, as requued by thc ~r.posals undu cemsidcration. Furthermore, aside from the projects listed below, we plan to brsng to 'I a committee of the DCE Board of Scientific Counselora fer approval all biochemical epidemiology projects with estua at ed costs esc eeding ;100,000. The following studies are being plamed during the initial two yracs of this contract: y, 1. Biochemical epid,emiology of lung cancer. A pilot case control study of lung cancer is planned which would include 100 newlydiagnosed, untreateJ cases and 200 m atched controls.Its goal would be identifying those apecific laborstory assaps whicb sp4eat to bald promise in ciartiymg tite brocne mic ai epidemiology of lung cancer. Study partici ants would be interviewed to obtain the usual demo- graphic information, data related to f ac tors thought to influeace the assays, a detailed smoking history and a reviaw of potentially carcinogenic environ- mental/occvpatiopal eaposures. Among the assays to be eraluated are carcinogen modified DNA in lympho- cytes;serum antibodies to tobacco smoke related earccnogen DNA adducts; carcinogen DNA idductsin ucine; DN A repair enzym e activity in lym phoc yt es; uciniury polynuclcar aromatic bydrocarbonsi drug metabolism phenotyping; and urinary eotinane to monitor ezprsuse to tobacco smoke. More specialized studies are planned for lung tis.we specimens(both normal and neoplastic) which are obtained from cases at the time of surgery. 'Ihese assays will be performed inhousc by LHC intramural laboratories, and include assays of oncogene ezpression,earcinogen activation, and measuremeata of DNA repair enzTme activity in both neoplastic and normal lung tissue. 2. Biochemical studies in tumors which occur excessively in blacks. As slaboratry ad,bnct to ' the series of populatinn based case control seudies of those cancers 4vhicb occur excessively in black The Cancer Letter Voi. 10 No. 43 / Page 5

Americans (approved by the boardlast jtme), bio- chemical assays will be performed to characterize diffcrences inblacks and whites, and when possible, cases vs. contrels. 'flte following are planned: pancreatic cancer (1100 cases and controls), Lewis blood ~roup type; prostate caacer (800 cases and conuols),bormones,nutrienta and viruses; multiple myeloma(700controlsonly),Quantitative rmtouno- globulinprofiles; eaopbageal cancer (600 controls only), nutrients. 1/ 3. Vrral studics in US. womta with carcinoim a of the uterine cervix. A case couQrol study of cervical cancer is currently under way in five U.S. compre- hensive cancer centers.Blood specimcns are being obtained from a sam ple of 500 cases of invasive eaneer,300womenwithinsitueareinoma and 1,000 controls, with the pri m ary f ocus being upon serum micronutrients. Prediagnosis blood samples are available on apprt+ximately 125 wom en.Thia atudy will be expanded to include serologic assays for herpes sunplex virus type 2, and human papilloma- virus (when a reliable test is available). l- 4. Laboratory studies in Oriental Ameriean women with breast cancer. A population based, c ase control int erview study of Clunese, j apanese and Filipino American women (600 cases and 1200 controls) with breast cancer is being planned among residents of San Fr ancisco Los Angeles and Oahu. Blood and trrine samples willbe obrained from study participants to assess nutrients and hort~tozes. !.• 5.Urine mutagens and carcinogen DNA in truck drivers. Several epidemiologic studies have ',docu- ©cnied an ~ccs~s ,Yof urinary,hladder cancer in truck drivers, an assocratior. that is M1dependc¢It of amoking status. Exposure to motor adhaiut fumes has beensuggested as a possible scurce of carcinogenic exposure in these men, with a leading hypothesis hano thsr Aire.l rvhAust fumra renrea.•nt the critical exposure. E:perimcntal support foa this hypothesis is derived from the fact that t1itro- polycyclic aromatic hydrocarbons are potent mutagens which occur at higher levels in diesel eompared with nondieael eshaust fumes. A pilot studt ia under coruideration in whicb nonsmo)dng tntckdnvcra who are exposed to (a) diesel fumes; (b) nondiesel fumes; and (c) no r ccent motor exhaust exposure, will be interviewed andprovide a urine sample to determine if mutagenactty and/or presence of carcinogen DNA adducts correlate with type of exposure. ( 6.DNA adducts in long tetm survivors of hlodg- kut's disease. From the original N CI cohort of 198 patients with Hodgkin's diseaae treated with com- bination chemotherapy (AfOPP) with or without radiation, 62 of 91 sttrvivors have been exam ined and have donated bone marcow as part of an attempt tc identify subclinical morphologic functional and cytogenetic abnotmalities which might charaQter- izeperstms at increased risk of treatment related acute leukemra.'llrese samples will be evaluated for the presence of DNA chemotherapy adducts. 7.EzQasuremeasurementsinworkers exposed to sol.•cnts.ThcOc:ul+ationalStudiesSectionof EEB is currertlF conducting two large cohort studies of wotkets with occupaponal esposures to potentially ;i r: . I - carcinogenic aolvents--dry cleaners exposed to perchlorocthylene, Hill Au Force Base aircraft mecbauics exposed to 1,1,1 trichloroethane. We plan a pilot study designed to teat the feaaibility of quantifying solvent exposures by measuring tolvent levels m the blood s.nd seeking the prestncc of DNA damage in blood lymphocytes. A small srtmple of studysubjects will be drawn from eachof the two cohorta for eseb of several solvent ezposur'e levels asdetermined by workhistory interviews and air m easulem eDts. I 8. Espustug mesarrementa in workers exposed to pesticides. The Occupational Studies Section is currentlystudym' gseverallargc cohorts of workers with occupational expostues to pot entially carcino- genic pssticides-atructtual peat control workers exposed toorganochlorine (especiall~ ehlordane), organaphosphate and carbamate pestiadea; and grain millers and handlers exposed to organochlonne compounds (especially ethylene dibromide). Using a pilot approach similar to that outlined for Eolvent workers, an attempt will be made to m easure chlor- dane and EDB levels in blood and to seek the presence of pesticide DNA adductsinblood andurine in an exposure stratified sample of workets from each of tbese two cohorts. 9. Laboratory studies in L atin A m eriean vvom en with ccrvic al canccr.'Ibe Environm cntal Studies Seetionisplatming a combined epidemiologicrlabor- atory study of 800 Latin American women with invasive cervical cancer and 1600 controls,,Also to be studied are the husbands of 400 sexually mono- gamous cases and 800 similar controls. Under a previously approved concept and contract, funds have been provided for assays of herpes simplex virus type 2,carotene and retinol in sera obtained from study participants. Under this proposed contract, fun#.e wmrld he nrovid.d to+mnnnrt enrtim.n shinm.nt from the field and sp ecim'enprocessing, amd for conduct of additional assays of interest, particu- latlyhuman papillomavirus, when a reliable sero- logic assay bccomes available. Tumor tissue wi.ll also be obtained for molecular studies. l0.Biochemicalstudies of oral caneer. A multi- center case control study of ora] and pbaryngeal cancer has been initiated (supported by another contract) to evaluate etiologic hypotheses regarding chewing tobacco,diet, mouthwash use, and occupa- tion;'The proposed contract would support a bto- chemical component to supplement the data obtained by interview, and would assess chromosal damage in exfoliated oral cells for several categories of individuals vie the micronucleus test, a procedure which has helped identify persons at high risk of oral cancer in other populations; and evaluate severity of disease upon blood levels of certain nutrients and possibly vital antibody titrea, and conduct casc control comparisons if extent of canc cr (Cnrginuedonpage 8) DCE ANNOUNCES RESOURCES AVAI t,ABLE T hr• niv. of Cancer Etiology of N Cl prepared the announcement on page 7 describing resources it is making available to the scientific community. The Cancer Letter page 6 / Nov. 9. 1984

Avran Myelobtastosbs Vrrus Reverse Transcnp• tase-2.000 Llmt Minimum Order Contsatx Lr?e SaQnces. Inc 29U0 72nd Stn*e1 North St Petersburg. FL 33710 t813) 346-93r1 Comg Contract +tNDt -CR 11013 fiostt S0 07/u:nt Plus Shipping Cetl Culture Identdreahon Service. Using Iso- lyme Analysis. Imm;rnolluorescence and Ka• ryotypic Analysis (Chromosome Banding) Contsptb Dr 1Nard Peterson Chddr'en; Hospital of Michigan 3901 Beaubren Boulevard Detrort. M! 48201 (313)494•5705 Citing Contract I N01-CR21017 Costtt $203 00rAnatysls Goat Anbsera against Avran. Bovme. Feline Murine. and Prrmate intact Viruses and Vrral Proteins Antrbodres, to Immunoglocul.ns for a number of species Prermmune Sera avaltaoie br some Virus AniBnra Conlsott Coordinator for Research Resources Blotogrcbt CarcrnoQenes,s B•anch. DCE. Nu. NIH Landow BI g . ~ ~ 9A22 Bethesda MD. (301) 49t-1951 QOatt $10 001ml Pius Shipping (Pre. Immone Sera-$5 OD+mI) Feline. Munne, and Primate Vr• Viruses Avian Baboon Sera Collected from An,mals m Sera trom Primates which were r.0used in the , ruses Prepared in T6ssue Culture Sukhu•m. USSR wrth High and Low Incidence U S and Irkcitculated with Material from the of Malignant Lymphoma Sukhumr Baboons Z.'O11lYQttt Ce::'d!nator fpr Research Resources Contacq Coordinator lot Research Contaels Coordinator br Research Biological Csrcrnogsirests Resources Resources NCI. /JIH Branch OCE Biological Carcrrog enesrs Biological Car ~•nogenesis . . Room ~3A2? Landon 81 Branch. DCE. NCt. NIH Branch. OCE. NCt. NIH 26200205 Bethesda Landow Bldg. Room 9A22 Landav Bldg Room 9A22 . (301) 496-1951 Bethesda. MD 20205 Bethesda. MD 20205 (301) 496•1951 (301) 496•1951 Cost Inquire Cosh Shipping Charges Only aGast Shipping Charges Only Human L3sues Car'c!nomas. Sa!comas. Melanomas. Lymphornas. Leukermas. Benign Tumors and other NOn-Mat~gnant Disorders Human Sera from dpnors with Carcinomas Sarcomas. Me!anomas. Lylnphorqlas. Leuke• mras Benign Tumors. Norrpat lndivrduats. Family Memhrns o1.Leukemics HematologiCal Diseases an.y othai Non-Malrgnant Drsorders Contao4t C:oordneitor for Research Resources Biological Caromogenesrs Branch. DCE. NCI. NIH 9A22 Lando+r,Bt~D 20205 Bethesda (301;496•195t Cpst1 Shipping Chartles Only Catton•Top Marmosets (S oedrpusl tor Use as Models for Carcrnogenes-s-Ho!dmg mocu:a• tron. ObservaLoh and Pathology Services are Avarlab!e Contactt: Dr Neal Clapp Marmoset Research Program Oak Ridge Assoc-ated Universities P06ox117 Oak Ridge TN 37831 6t5) 576-4103 dmg Contract AN01•CR21004 Gostt $10 00 per d!em (or higher tor procedures rnvotvrng additional Care- etc ) 51000 per Dlood sample Chemical Carunog'en Relerence Standard Repository Reference ouantrhes of nearly 700 com pounds are aYarlabpe Included are numerous representatives of the lollowing c!asses po!y nucloar ammathc hydrocarbons. PAH meta7obtes raorotabeleo PAy metabontues. nitrogen het• e'ocyJe5 ndmsarrmrnesmrtrosamrdes- aromaUc amines aromatic amine metab0!ites rad,olabeted retmoods. azoa7oxy aromatics. !norganres. mtmaromahcss peshc des. p'+armaceu. U,:ats natural products_ dyes droxms chlonnated alrphab_s and miscellaneous groups Data sheets pnovrded with the compounds. include chemical and physKal propertres anatyt:cai data- hazards_ storage and handlirg information Catalog available upon request Contacts Coordm3tor tor Chemical Research Resources Chemical and Physical Carcmogenesrs Brancn. DCE NCI Landow Bidq Am 9801 t3emesda 4(D 20205 1301) 436 0471 COath Subleci to chemical ctass code and quantity (sez cataloal •E~idemiotogy The Immunotleticrency--Cancer Registry (ICR) is a unique registry of cancer cases that occur in patients with naturaeyCCCUrn[ca rm, munodei,crencres Case material couected by the ICR comes Irom case repons appearing in sc.entrbc literature and voluntary reporbng by physicians Cr!tena tor inclusion rn the registry are clm!cat o• labo'atory evidence of a pnma• ry rmmunedehc-ency synOrome pnOf Ib the onset of m3ugnancy Data contained in the ICR are avartab!e to the extramural research Communrry for the ptannrng_ design. and c6i duct Ot PesearCh efforts Limited assistance is available to investigators interested in utdrzrng the 'ee,qtry Contaau Dr Alexandre H Fdipo..ch Immur!odef crency-Cancer Regrstry Box 610 Meyo Umvers•ty of Minnesota Minneapolis. MN 554SS (612) 376-2174 Citing Contract rN01•CP3•1011 The Tumor Vrrus Eprdemnotogy Reposrtory (TVE R) contains sera and other bro!og•cai samples from more than 13 000 patrents and controls obtarned in 12 different countries The TVER was established primarily to supporl collaborative research on the rote of E pste:n Barr virus (EBv; +n Burkr115 tymphoma nasopharyngeal carcmoma and retated d-s- eases Pan of the collection includes sera that were obtained from nonhumin pr,mates •^a[u lated with EBv The TVEFI rs able to adtust ds cotlec!•on to ta crtnatc :he development nt new couaborat-ve stud~es rn adddhon some sampres are ava•, able to• reagents and independent research The most e>'rensive collecbons are serum samples from patients with Burkrtls !y^IphOma (sera Porn more than 1000 pai•en'S1 {.'oHtaCtt Dr Paul H Levine Co. t: Ctm~cal Ep~dem,o'~gv Brancn DCE NC! NrH landow E9uOd••+g Room &:41 Be',esoa MD:G:3:, ;3011 496 `067 ... f r('[• !r` Con3hn'.f' r^ ~.Yci C,i - Othe`s-Sh.pp:nq Cr.a•yes 0- r The Cancer Letter Vol. 10 ho a3/Page7

ft E has not influenced the blood j.evels. 11. Biochemical epidenniologic studies in Cauins. A series of case control studies of cancer are under way in high risk areas of China. Etiologic factors for cancers of the esophagus, lung, stomacla and cboriocarcinoma are being assessed via interview and labort+tory study funded by a contract with the - - - - - - - - - - - - - - - - - - - - - - - - - - OUNCBPT RB1I183P FICtl71tBS ARE BS'lI9oA'133S ON1.'t: kFPs, RFAs NOT YBT AVAILABLE The dollar estimates with each concept review brought before the vaeAous bodrds of scientific counselors are not intended to represent maamtdm or exact amounts which will be spent bn those projects. They are intended only as kumles for board members to help ittdetermining the value of the projects in relatton to resources available to the entire program ordivision. Responses should be baaed on the workscope and description of goals ard methoda included in the RFPs (contracts) and RFAs (grants and cowpecative agreements). Availability of RFPa and RFAs will be atmounccd when:h.e Institute is ready to release them. -------------------------- Cancet lnstitute of the Chinese Academyof Medical Scienc es. Support from the pr ed cotttr ac t would supplement the existing effort in two ways-by providing for replication of certain assays to assist in ycality eonerol, and by providing for additional nssaya that cannot now be reliably con- ducted in Chrrta. Mark Gtecne and Dean Mann are the project officers. °'Ihis ia a well conceived project," Board member Hilary Koprowski commented. "It is long overdue." "Ibis will be of terrific assistance to intca- mural researcht"Board member Gilbert Omenn said. "Would this knowledge be useful to extramural investigators? Can we make it available to all principai investigators and prospective applic antst This will advance the whole initiative of bro- chemical elidemiology.I think it is important to share this. Greene said the information would be made available to anyone. "'Ihe epidemiology bFanches are in an unfair sintation; Board member Myron Essex said."Wet labs can change directiorta by pauchasing new mat erials by transferring aup lies money from one area to atmthex. When epu~emiology takes s new direction, it has to be presented as new research:' (More concepts approvkd by the DCE Board wili appear in ne:t week's issue of 'llue Cancer LetterJ. Requests fot proposal described here pertain to coottacts platmed for aw•azd by thc National Can cc r I®stitute unless otherwise not ed. NCi liatiogs will show the phone taimber of the Cchntractittg Officer or Coa:tract Spcdalist who will respond to questions. Address requests for NCI RFPs citing the RFP adtmber, to the iocbvidual natoed, le Blau building room tauobashown,National Cancalostitute~ NIH Bethrada, MD. 20205. Proposals may be hand dehvereJ to the Blair building, 8300 Colesville Rd., Silver Spring Md., but the U.S. Postal Service will not d~}iPa ttere. RFP anaoamcementa from other sgencies v11'wclude the complete mailing address at the end of each. RFP NCl-CN-55443-20 Title: Operations office for anter-instiRnrional necleaa magnetic ttesonanee (NMR) studies. Deadline: Jan. 4 N CI's Drv. of Cancer Prevention g Control is solidting proposals from organizations interested in establishing an NMR operations office to organize anetwork of NMR laboratorxes to carryout rtsearcb in the detection and diagnosis of cancer.lt is the intent of this contract to initiate inter-inatitu- tional studies among NMR laboratories which are already contributing to cancer research. This proposedprocurementissubjeet to the availability of funds. Contract Specialst: Joan O'Brien RCB Blair Bldg Rm ,4A01 301-427-8745 NCI CONTRACT AWARDS 7111E: Preparation of monoelonal/monospecific antibodies to oncogene products of avian and mammalian retrov'truses CONTRAC7DR: Scripps Clinic & Research Foun- dation. $1,885,246. 'il1'LE; Application of the human tumor colony forming assay to new drug screening aDN'IR AC'I0RS: tkiv. of Arizona,;809,9 R5; Univ. of California (Los Angeles), $596,656; and Msyo Foundation, $687,700. TlTLE; Collection, storaget quality assurance and distribution of biological response mod- ifiers CON'1`RAC'PDR: Meloy Laboratories,;1,232,251. TTTLE: Partial support of Institute of Lab- oratory Animal Resources CONTRACTOR: National Academyof Sciences, $18S,00Q. 'RTLE: Tracingindividua)s for environmental =pi- demiologic studies of cancer using vital statistics records dDNTRAC7UR: WestatInc„)S7S,000. TheCsncer Letter _Editut Jer,v D. Bov d • • PyVhtrC. ~~ .v~fi]^I 1•mP1a NfP b. " : C.- -.r ti...,.. i-. . r . I ..•. . .' V:,... \ •j •. . .. "` - :1 . t .. • , ~I inr C•.• ._ , C I ~ t .