Cmparisn f Age- and Sex-Specific Incidence Rate Patterns f the Leukemia Cmplex in the and the 009 1, 2 Rbert Schneider 3, 4 ABSTRACT-Data n cancer cases in cats and dgs ere cllected systematically by the Animal Neplasm Registry f Alameda and Cntra Csta Cunties, Calif., a ppulatin-based animal tumr registry. Etilgic relatinships ere evaluated n the basis f cmparisns f age-specific, sex-specific, and age-neutered-specific incidence rate patterns f the leukemias. Age-adjusted annual incidence rates fr all leukemias per 100,000 cats r dgs ere 224.3 and 30.5, respectively. The cat had 6.1 times mre malignant lymphmas and 15.7 times mre myelprliferative disease than the dg. Feline age-specific rates indicated abimdal age pattern fr all leukemias and fr malignant lymphma alne and a single early peak fr myelprliferative disease. In the dg, all age-specific patterns increased ith age and peaked later in life. Feline sex-specific, age-adjusted rates shed that the neutered female as at lest risk, flled by the neutered male, entire female, and entire male. In the dg, the neutered male as at lest risk hile the ther three sex categries ere clustered. Hever, the magnitude f expressin ithin each species separately as the same fr the neutered male, entire male, and entire female, but nt fr the neutered female. Neutering decreased the risk f leukemias in the female cat by apprximately ne-half but did nt affect the risk f leukernlas in the female dg.-jnci 1983; 70:971-977. Study f the natural expressin f cancer in dmestic animals has been limited because flack fadequate animal data. Animal tumr cllectins traditinally either have been designed t gather nly representative cases f varius types f tumrs, r, if brader in cncept, as are mst veterinary schl cllectins, tend t have tumr distributins that may nt be representative f the nrmal ppulatin because f referrals and the specific interests f the faculty. T achieve representativeness, sme studies have utilized cmbined animal cancer data frm a number f veterinary schls (1-7). Adequate ppulatin-at-risk data fr calculatin f incidence rates have als been a prblem. The clsest t the prbable true ppulatin at risk in the abve-cited studies has been achieved by use f the patient ppulatin frm hspitals r clinics included in the study. Hever, such ppulatins may cntain varius types f bias (8). A ppulatin-based animal tumr registry cvering a defined gegraphie area, in the traditin fhuman registries, uld represent a mre psitive apprach t the achievement f representativeness f bth cases and ppulatin at risk. Such a registry has been active as the ANR. The ANR develped methds f systematically cllecting cancer cases diagnsed by veterinarians in resident animals f a defined gegraphie area (9) and f peridically btaining estimates f the animal ppulatins at risk by surveys (TO). T fully evaluate etilgic relatinships fund in animals and apply such knledge t understanding the human cancer prblem, ne needs t have knledge n cancer expressin in defined animal ppulatins. Such knledge uld include incidence rates fr varius demgraphie parameters, such as age and sex. The present study cmpares age-specific, sex-specific, and "age-neutered"-specific incidence rate patterns f the leukemia cmplex in cats and dgs. Age-neutered-specific incidence rates are a ne cncept; they are calculated separately fr specific ages at neutering subppulatins ithin chrnlgical ages. MATERIALS AND METHODS Fr this paper all cancers f the leukemia cmplex ere divided int t categries, malignant lymphma and myelprliferative disease. Malignant lymphma included all slid lymphcytic cancers and lymphcytic leukemias. In the dg and the cat, lymphcytic leukemia rarely ccurs ithut slid lymphcytic invlvement. Myelprliferative disease included nly malignancies frm erythrcytic r granulcytic stern cells t mre differentiated cells f the t bne marr series. The case grup included nly thse cases histpathlgically cnfirmed. Practitiners ere asked t submit tissues, including bld and bne marr smears, frm all pssible tumrs. T encurage cperatin, the ANR paid all csts fr submissins including diagnstic csts fr histpathlgy and sent a cpy f the diagnsis t the submitting practitiner ithin a fe days f receipt f a specimen. Tissue examinatin as dne by cntract ith a human hspital pathlgy labratry in the gegraphie area. As a randm quality-cntrl measure, ithut knledge f the labratry diagnsis every tenth submissin as autmatically revieed by Jack E. Multn, Department f Veterinary Pathlgy, University f Califrnia, Davis. Of the first 545 cases revieed in 5,477 submissins, agreement ith and acceptance f the cntract labratry diagnsis as crrect ere 92.5%. Further details f the ANR methdlgy ere described earlier (9). Incidence rates ere calculated by using 1 years f cases first diagnsed beteen July 1968 and June 1978 as nurneratrs. Denminatrs ere ppulatin estimates btained by averaging t surveys dne as f December 31, 1970, and as f December 31, 1975. Sex categries ere designated as neutered female, entire female, neutered male, and entire ABBREVIATIONS USEO: ANR=Animal Neplasm Registry f Alameda and Cntra Csta Cunties, Calif.; FeLV=feline leukemia virus. 1 Received September 28, 1982; accepted December 17, 1982. 2 Supprted by Public Health Service grant CA-14916 frm the Natinal Cancer Institute. 3 Animal Neplasm Registry, Department fepidemilgy and Preventive Medicine, Schl f Veterinary Medicine, University f Califrnia, Davis, Calif. 95616. 4 I thank Ms. Gretchen Luise Bradfield and Ms. Mari-Arm Green fr their technical assistance. Dnladed frm http://jnci.xfrdjurnals.rg/ at Pennsylvania State University n May 8, 2016 971 JNCI, VaL. 70, NO. 5, MAY 1983
972 Schneider male. Fr each case, the sex categry at the time f first leukemia diagnsis as used and fr the ppulatin it as the sex categry as f the dates f ppulatin estimates. The denminatrs fr the age-neutered-specific incidence rates ere the crrespnding age hen neutered subppulatin ithin each chrnlgical age f the neutered ppulatin. Age at neutering as available fr mst cases. It as derived frm a cmbinatin f ne f the flling: date neutered and data f birth r date neutered, date f diagnsis, and age at diagnsis. Animals ith unknn ages at neutering ere prprtinately distributed accrding t the knn ages ithin a chrnlgical age grup. Data n age hen neutered fr the ppulatin at risk ere cllected in the 1975 survey nly, and the prprtins fund ere applied t the 1970 and 1975 averaged ppulatins. Ageneutered, age-specific rates ere calculated fr each neutered sex ithin species fr 6 chrnlgical age grupings: under 1, 1, 2, 3, 4-8, and ver 8 years. T facilitate cmparisn ithin each species, the age-, sex-, and age-neutered-specific rates ere age standardized by the direct methd t a standard ppulatin by age. Fr the calculatin f the age-adjusted, age-neutered-specific rates, the age-specific incidence rates f the nnneutered cases ere used fr the chrnlgical ages prir t neutering age. This prcedure as flled fr t reasns: 1) Nnneutered expressin may have influenced subsequent neutered expressin at a variable frequency ith age, and 2) the adjusted rate uld be distrted if nly expressin frm the age hen neutered as cmpared ver the life-span f the cat fr the 6 chrnlgical age grupings. S that cmparisns culd be made beteen these species, the ppulatin standard f the cat as adjusted t that f the dg t reflect the average survival differences after maturity fund beteen the t species. Table 1 shs the divisin TABLE 1.-Ppulatin standard by age fr the cat and the dg that equates the expected survival time beteen species Age, yr <1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 Ttal Standard ppulatin, N. 31,258 11,608 5,408 5,248 5,021 4,940 4,716 4,310 3,875 3,872 3,501 3,208 2,849 2,612 2,196 1,702 1,369 957 638 712 a 100,000 a Includes all ages abve this age als. Dg 27,061 13,134 6,418 6,395 6,056 5,855 5,526 4,793 4,649 4,213 3,739 3,270 2,903 2,156 1,653 1,046 643 490 a 100,000 TABLE 2.-Case numbers and average yearly ppulatin at risk fr the cat and the dg Disease-sex categry Allieukemias Entire <:2 Unknn sex Malignant lymphma Entire S' Unknn sex Myelprliferative disease Entire S' Unknn sex Ppulatin at risk Entire S' Unknn sex Cancer type Crude Case N. r average yearly ppulatins at risk 3,905 869 1,458 557 1,004 17 2,689 614 1,054 401 605 15 1,216 255 404 156 399 2 171,228 61,461 45,682 25,744 37,364 977 Incidence rates Age-adjusted Crude Dg /dg rati f age-adjusted rates Age-ad- justed Dg 817 237 33 169 378 714 202 28 141 343 103 35 5 28 35 260,570 64,691 11,233 64,025 118,874 1,747 TABLE 3.-Crude and age-adjusted incidence rates fleukemias per 100,000ppulatin fr the cat and the dg All leukemias 228.1 224.3 31.6 30.5 7.4 Malignant 157.0 159.9 27.6 26.4 6.1 lymphma Myelprliier- 71.1 64.4 4.0 4.1 15.7 ative disease by age f the ppulatin standard fr each species, adjusted t a ttal ppulatin f 100,000. RESULTS There ere 3,905 cases fleukemia diagnsed in the cat and 817 in the dg during the 10 years beteen July 1968 and June 1978 (table 2). Malignant lymphma cmprised 68.9% f the cat cases and 87.4% f the dg cases. Myelprliferative disease accunted fr the remainder f the cases. The ttal average yearly ppulatins at risk ere 171,228 cats and 260,570 dgs. Crude and age-adjusted annual incidence rates per 100,000 ppulatin fr all leukemias in the cat ere 228.1 and 224.3, respectively; in the dg, the same rates ere 31.6 and 30.5, respectively (table 3). Cmparing the age-adjusted rates beteen the t species indicated that the cat had 7.4 times mre leukemia than the dg. Table 3 als shs the Dnladed frm http://jnci.xfrdjurnals.rg/ at Pennsylvania State University n May 8, 2016 JNCI, vr., 70, NO. 5, MAY 1983
Cmparisn 01 Age- and Sex-Speci1ic Leukemia Rates 973 m r-- ON.0 O ON 0:: 0 CL N I- 0 ::~ u Z ~ Cl U =~ --l :::::l0 Z", Z ~O U> ::> :;:: 0.0 2.0 4.0 6.0 8.0 10'.0' 12'.0' 14'.0 16'.0 18'.0 20'.0 AGE IN iears l.-age-specific incidence rate pattern fr the cat f all leukemias (ML+MD), fmalignant lymphma (ML), and f' myelprliferative disease (MD). TEXT-FIGURE crude and age-adjusted rates fr malignant lymphma and myelprliferative disease. The cat had 6.1 times mre malignant lymphmas and 15.7 times mre myelprliferative disease. Feline age-specific rates indicated abimdal age pattern fr all leukemias cmbined and fr malignant lymphma alne (text-fig. 1). The myelprliferative disease pattern had nly ne age peak, an early ne. In the dg, all agespecific patterns increased ith age and peaked later in life (text-fig. 2). ML MD Sex-specific, age-adjusted rates shed marked differences ithin the feline species and limited differences ithin the canine species (table 4). In the cat, the neutered female as at lest risk, flled in rder by the neutered male, entire female, and entire male. The difference beteen the neutered female and entire male rates as apprximately threefld. In the dg, the neutered male as at lest risk, ith the risks fr the neutered female, entire male, and entire female elustered else t each ther near 1.0. Cmparing the relatinships ithin the fur sex-specific, 0 0.0> CL (X) CL O 1-... CL ~ u :: 2~ u -.J... ::J 0 m CJ 0 N ::> 0 0.0 2.0 4.0 6.0 8.0 10.012.014.016.018.020.0 AGE IN iears TEXT-FlGURE 2.-Age-specific incidence rate pattern fr the dg f all leukemias (ML+MD), fmalignant lymphma (ML), and fmyelprliferative disease (MD). TABLE 4.-Sex-specific, crude, and age-adjusted incidence rates f leukemias per 100,000ppulatin fr the cat and the dg Incidence rates Incidence rates Disease-sex categry Dg Crude Age-adjusted Rati" Crude Age-adjusted Rati" Allleukemias Neutered ~ 141.4 147.7 1.0 36.6 27.9 1.0 319.2 292.8 2.0 29.4 20.8 0.7 Entire ~ 216.4 354.5 2.4 26.4 29.5 1.1 268.7 464.9 3.1 31.8 34.0 1.2 Malignant lymphma Neutered ~ 99.9 105.9 1.0 31.2 23.8 1.0 230.7 216.2 2.0 24.9 17.5 0.7 Entire ~ 155.8 263.5 2.5 22.0 24.5 1.0 161.9 338.0 3.2 28.9 30.3 1.3 Myelprliferative disease Neutered ~ 41.5 41.8 1.0 5.4 4.1 1.0 88.5 76.6 1.8 4.5 3.3 0.8 Entire ~ 60.6 91.0 2.2 4.4 5.0 1.2 106.8 126.9 3.0 2.9 3.7 0.9 Dnladed frm http://jnci.xfrdjurnals.rg/ at Pennsylvania State University n May 8, 2016 a Age-adjusted rates divided by the neutered female age-adjusted rates ithin each cancer categry. JNCI, VaL. 70, NO. 5, MAY 1983
974 Schneider T ABLE 5.-Cmparisn f sex-specific, age-adjusted incidence rates fleukemias shing the same rati frequencies fr entire male, entire female, and neutered male in the cat and the dg Disease-sex categry a Ratis that agree beteen species. g ~ age-adjusted rates (table 5) beteen the t species shed that the neutered male, entire male, and entire female rates ere prprtinately the same beteen species but that the neutered female rates differed. Except fr myelprliferative disease in the dg here l rates ere present, hich culd have cntributed t larger variability, the rati fthe entire male rates t the entire female rates in bth species as apprximately 1.2: 1.4. The rati f the entire male rates t the neutered male rates as 1.6: 1.7 in bth species. Hever, cmparisns ith female rates indicated neutered fe- ~ 00 ~~ a...g N I CI 0 g u... 0 u:il -1 0 CI ~ CD CI (!)... CI >0 re TEXT-FIGURE 0.0 2.0 4.0 6.0 8.0 10.0 12.0 14.0 16.0 18.0 20.0 AGE IN YEARS Ratis fr: EH Dg All leukemias n 1.8 1.0 Entire /entire ~ 1.3 a 1.2 a Entire /neutered 0 1.6 a 1.6 a Neutered ~/entire ~ 0.4 0.9 Malignant lymphma n 1.8 1.2 Entire /entire ~ 1.3 a 1.2 a Entire /neutered 0 1.6 a 1.7 a Neutered ~/entire ~ 0.4 1.0 Myelprliferative disease n 1.9 0.8 Entire /entire ~ l.4 a 0.7 Entire /neutered 0 1.7 a 1.1 Neutered ~/entire ~ 0.5 0.8 3.-Age-specific, sex-specific incidence rate pattern fr the cat f alileukemias. EM=entire male, EF=entire female, NM=neutered male, and NF=neutered female. EF NH NF male:entire female ratis f 0.4:0.5 in the cat and 0.8: 1.0 in the dg. Thus cmpared t the entire female rate, neutered rates indicated that neutering decreased the risk f all leukemias in the female cat by apprximately ne-half but did nt appear t affect the risk in the female dg. The feline sex-specific age rate distributins (text-fig. 3) appeared t have 4 age grupings int hich the age-specific patterns fr each sex culd be divided fr smthing: under 1 year, 1-3 years, 4-8 years, and ver 8 years f age. The under-1-year-f-age rates fr all sexes appeared t be the same. The 1- t 3-year age grup frmed the first peak, hereas the secnd age peak as frmed in the grup ver 8 years f age. ith the use f these age grupings, t distinct patterns, an entire ne and a neutered ne, became apparent (text-fig. 4). In each pattern, the female cat as at ler risk. Althugh nt as bvius as in the cat, there als appeared t be sex-specific differences f a l rder f magnitude in the dg (text-fig. 5). These differences ere f t types, ler expressin at all ages in neutered males cmpared t neutered females, hich resulted in neutered male rates being apprximately 75% fthse fneutered females (table 4), and reduced expressin t 3 years f age in bth the neutered male and female hen cmpared t the entire male and female. Age-at-neutering rates (table 6) indicated that the chice f neutering age and the sex had prfund interactins n hether neutering decreased, increased, r did nt change expressin, hen cmpared t the expressin amng nnneutered animals. Overall, except fr neutering in fern ale 0"" 00 0 0... r-- a...g CD I ~ U 0... 0 u... -1 0 CI ~(l') '" g (!)N >0 ~ 0.0 2.0 4.0 6.0 8.0 10.012.014.016.018.020.0 AGE IN YEARS TEXT-FIGURE 4.-Age-specific, sex-specific incidence rate pattern af all leukemias fr the cat < 1 yr, 1-3 yr, 4-8 yr, and >8 yr afage. EM=entire male, EF=entire female, NM=neutered male, and NF=neutered female. EM EF NM NF Dnladed frm http://jnci.xfrdjurnals.rg/ at Pennsylvania State University n May 8, 2016 JNCI, VOL. 70, NO. 5, MAY 1983
Cmparisn f Age- and Sex-Specific Leukemia Rates 975 m "0 000 O CL<- ~ 0 <D U Z LI'l C) u Z......J :::J ZO z'" t.:) "" :> ~ 0.0 2.0 4.0 6.0 6.0 10.0 12.0 14.0 16.0 16.0 20.0 AGE IN iears TEXT-FIGURE 5.-Age-specific, sex-specific incidence rate pattern f all leukemias fr the dg <1 yr, 1-3 yr, 4-8 yr, and >8 yr fage. EM=entire male, EF=entire female, NM=neutered male, and NF=neutered female. TABLE 6.-Age-adjusted, age-neutered incidence rates" fall leukemias per 100,000 female and male cats and dgs Age neutered, yr Age-adjusted, age-neutered leukemia incidenee rates per 100,000 ppulatin f: Neutered Neutered Neutered Neutered female eat female dg male cat male dg <1 119.3 29.0 188.1 1 117.1 29.0 237.1 12.6 2 166.8 34.2 232.3 12.4 3 153.3 16.0 340.9 27.4 4-8 193.2 21.2 576.1 26.1 >8 331.3 49.5 608.6 43.6 Nt neutered" 330.4 29.1 397.0 29.2 a In ealeulatin f an age-adjusted rate fr the chrnlgical ages prir t the neutered and chrnlgieal ages agreeing, the age-speeific incidence rates f the nnneutered grup ere used. b Cmparative nnneutered rates ere used fr this cmparisn; nnneutered rates here differ frm thse given in table 4 because f different cmbinatins f age grups and the eliminatin f the unknn ages. dgs, neutering befre 3 years f age deereased leukemia ineidenee. Female dgs neutered befre 3 years f age expressed the same ineidenee as nnneutered females. In the grups neutered at ages 3-8 years, there generally as deereased expressin (exeept fr male eats in the 4- t 8-year age grup); hever, females shed mueh mre deereased expressin than males. In the age grup ver 8 years, expressin as either the same (female eat) r inereased apprximately 1.5 times, hen empared t the expressin in nnneutered animals. EM NF EF NM DISCUSSION Cmparisn f leukemia expressin beteen the dg and the eat indieated markedly higher rates in the eat fr bth malignant lymphma and myelprliferative disease. Fr all leukemias, the rate in the eat as 7.4 times higher than that in the dg n the basis f emparative age-adjusted ineidenee rates (table 3). In additin, a majr prtin f feline eases as expressed at early ehrnlgieal ages. These bservatins euld supprt an etilgy invlving an in fectius agent such as FeLV eausing leukemia in the eat, as is believed t be the ease by many researehers. Hever, as indieated in table 5, the sex expressin relatinship fr entire males, entire females, and neutered males as the same fr the eat and the dg. Ifne assurnes that FeLV causes feline leukemia, then the territrial habits f male eats uld render them mre highly suseeptible t infeetin ith FeLV and lead t an exeess feline male expressin as bserved. Breeding entaet in entire females euld render them mre highly suseeptible als. Henee there euld be ensisteney ith FeLV infeetin and feline disease t this pint. Hever, n infeetius agent has been fund asseiated ith leukemia in the dg. hy then des the dg have the same prprtinal sex expressin as the eat, ith the exeeptin fthe neutered female, unless etilgy and/r pathgenesis have smething in emmn? Anther majr questin still t be ansered is hether the magnitude f the expressin variatin beteen these speeies euld be due nly t etilgie reasns such as FeLV, r hether it euld be due partially r ttally t intrinsie speeies differenees such as thse invlving immunlgie empetenee. A eritieal ensideratin ith regard t immunlgie empetenee euld be the magnitude f the early age peak fr leukemia bserved in the eat (text-fig. 1) but nt present in the dg (text-fig. 2). If ne ensiders all the immunlgie stresses in the yung, and espeeially the many different feline viral disease agents empared t the fe such agents in the dg, the eat's immunlgie system n a ppulatin basis may be mre stressed than the dg's. ith inereasing number r timing f insults, the immunlgie system f the eat may beeme less prteetive and/r may enhanee eertain lympheyte clnes t prliferate; henee mre and earlier leukemias eeur in that speeies regardless f FeLV aetivity. As has been previusly shn (11, 12), the bimdal age-speeifie pattern f feline leukemia is almst exactly like the bimdal age-speeifie pattern f human Hdgkin's disease, hieh als shs a large, early age peak. Of all the human leukemias, Hdgkin's disease is thught t be the mst likely eandidate t have a speeifie infeetius agent etilgy, althugh an agent has thus far eluded disevery despite large research effrts. Similar t cats, humans harbr many viral disease agents. Perhaps then the etilgy f leukemias, espeeially the lympheytie varieties, is mueh brader in eneept than just a single ne-agent hypthesis, even in the eat. ithin the variables tested in this study, leukemia expressin appears t be intrieately invlved ith the sex f the dg r eat and as aseparate entity, presenee r absence f sex hrmnes due t neutering in bth males and females. hatever the etilgie ensideratins, mre male expressin empared t female expressin as present in bth the dg Dnladed frm http://jnci.xfrdjurnals.rg/ at Pennsylvania State University n May 8, 2016 JNCI, VOL. 70, NO. 5, MAY 1983
976 Schneider and the cat as in man. hen nly rates fr all leukemias in entire dgs and cats ere cmpared, there as an apprximate range f 20% mre male expressin in the dg t a 30% excess expressin in the cat (table 5). Human subppulatins in the United States als sh variable percent excesses f male ver female age-adjusted leukemia rates, sme in the same ranges as thse in the cat and the dg, but mst falling beteen 40 and 60% r apprximately t times the dg t cat excess percentages (13). It has been hypthesized that the majr reasn fr excess human male cancer at mst sites as a mre efficient immunlgic system in human females (14). Female dgs and cats als appear better able t survive in ur envirnment than their male cunterparts, fr in bth species, as in humans, the survival gap cnsistently idens beteen male and female ith increasing age (10). Mrever, in an unpublished analysis f mrtality data fr dgs and cats cllected in the t ppulatin surveys used in this study, fern ales had ler age-adjusted, disease-nly mrtality rates amng bth neutered and entire grups than their male cunterparts. In cntrast t humans, dgs, and cats, ther species fr hich there have been sufficient data available tend t have excess expressin f leukemia in the female. These speeies are the muse (15), rat (16), guinea pig (17), hrse (7), and c (7). Thus the leukemia patterns f humans, dgs, and cats differ in sex expressin preference frm the ther named species. The reasns fr this difference may be imprtant in understanding the etilgy and/r pathgenesis fleukemia and hy sex hrmnes can affect risk. The t mst bvius differences are physical envirnment and diet. The dg and the cat tend t share clsely the same physical envirnment f man, and sme aspects f this envirnment may relate t male leukemia excess. It is als pssible, hever, that diet may be mre imprtant, in that humans, dgs, and cats eat meat and animal prducts as a majr dietary surce, hereas the ther species d nt. Perhaps animal-surce sterid r prtein metablism is in sme ay invlved. In additin t male-female differences, effects f sex hrmne remval via neutering ere als present (text-figs. 4, 5). The effects f neutering appeared t be related partially t species, partially t sex, and partially t the age hen neutering ccurred. Species and sex differences ere fund in the fernale nly. In the males fbth species, entire male age-adjusted rates ere apprximately 60% mre than neutered rates, hereas fr the neutered fern ale cmpared t the entire female, there ere marked differences beteen dgs and cats (tables 4, 5). There as little r n change due t neutering in the female dg, here neutered expressin as almst the same as the entire expressin. Hever, in the fern ale cat, neutering reduced expressin by apprximately 40-50% f the entire fern ale age-adjusted rate. The reasn fr these female differences as nt clear and shuld be pursued further, especially since males f bth species shed the same magnitude freduced risk frm neutering. T areas that might be fruitful fr study are the differences in estrus cycles beteen species and the effect fpregnancy, hich uld generally ccur mre frequently in cats. Neutering in three strains f mice (15) resulted in higher leukemia expressin in thse neutered, hich as exactly ppsite t the results shn in this paper fr thedg and TABLE 7.-Ratis fprir age-adjusted, age-neutered incidence rates falt leukemias divided by the subsequent rates fr female and male cats and dgs Ages in ratis, yr Ratis fr: Neutered Neutered Neutered Neutered female female male male cat dg cat" dg <1/1 1.0 1.0 0.8 1/2 0.7 0.8 1.0 1.0 2/3 1.1 2.1 0.7 0.5 3/4-8 0.8 0.8 0.6 (1.0) 1.0 4-8/>8 0.6 0.4 0.9 (0.6) 0.6 a Numbers in parentheses indicate rati values if age-adjusted incidence rate f male cats neutered at 4-8 yr f age as ::::340/100,000 instead f 576.1. the cat. Neutered male hrses and cs (7) als had excess leukemia expressin as as fund in the muse. Thus there appears t be a cnsistency f ppsite neutering as ell as ppsite male-female effects in the dg and the cat and perhaps man als, hen cmpared t the effects seen in rdents and herbivres. In additin, age at neutering appears t be imprtant in the neutered risk effect fr bth males and females (table 6). It is bvius that the majr part f the reduced risk effect f neutering in the feline fernale and male and the canine male as due t neutering befre maturity (table 6). Interestingly, there as a definite pattern f increasing and decreasing risk t the ratis btained hen prir age-adjusted, ageneutered leukemia incidence rates ere divided by subsequent age-adjusted, age-neutered ineidence rates (table 7). The same pattern as present in the female regardless f species. Thus even thugh neutering did nt affect the leukemia expressin f the female dg, age at neutering shed a similar pattern f risk effect as seen in the female cat, here neutering reduced leukemia expressin by apprximately 40-50% (table 5). ith a slight reductin in the 4- t 8-year incidence rate f the neutered male cat, a similar rati pattern culd als be seen in males f bth species, here the effect fneutering as the same (table 7). Further rk is necessary t gain an understanding f the pattern f increasing and decreasing risk effect f age at neutering. In summary, age and sex preferences f leukemia expressin in the cat and the dg resemble thse in humans. The sex preference cntrasts ith hat has been previusly fund in sme rdent and herbivre species. In additin, neutering reduced risk markedly in the fern ale cat but less s in the male cat and dg and did nt appear t affect risk in the female dg. 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