Document a4mK6RGZQxZKBMYgv2B3XOgBR

87. [Risk factors analysis of leukemia and aplastic anemia in China. Chinese Epidemiologic Study Group of Leukemia and Aplastic Anemia]. Chung-Kuo i Hsueh KOHsueh Yuan Hsueh Pao Acta Academiae Medicinae Sinicae, I-'& J 1992 Jun, 14(3):185-9. J'1 Language: Chinese. (UI: 93008605) Abstract: Based on the incidence survey of leukemia and aplastic anemia (AA) from 1986 to 1988, Case control studies (1257 new leukemia cases and 339 new AA cases) were carried out according to the type of leukemia and AA in order to better understand the epidemiologic characteristics of the diseases. Controls were matched randomly (age, sex and ethnic group) from the same population. The data were analyzed with the conditional Logistic multi-regression model and calculated on an IBM-PC/XT. The risk factors of M2a were found to be X-rays, antipyretics, benzene, pesticides and bimolane; that of M3 was chloramphenicol; that of M5 was X-rays; and that of other ANLLs was phenylbutazone. The risk factors of ALL were chloramphenicol, phenylbutazone and family members with cancer: those of CML were X-rays and hepatitis; those of CLL were chloramphenicol and benzene; those of AAA were antipyretics and hepatitis; and that of CAA ws X-rays. i f 1 &&;%E&&@@B%h%%*& Table 1 Type distribution of the cases studied M2a NO. of cases 193 NO. of coutrol 386 A NLL M2b M 3 't M5 Others) A L L CML CLL AAA CAA -. 26'12 171 178 309 152 3 "I?. 3G7 24 312 356 416 618 304 68 144. 534 M2a M 3ANLLM 5 Other ALL CML CLL AAA CAA X-ray 1.24' 1.15 1.47** 1.09 1.10 1.71** 1.23 0.93 1.82" Chloramphenicol 0.96 1.90' 1.34 1.28 1.96.' 1.52 2.83' 2.13 1.37 Antipyretics a~l~Antireumntics Birnolane 1 TO** 0.84 4.@0" 1.25 0.64 - 1.10 C.37. - 1.07 1.18 1.40' -1.64' 2.45* 1.43 2.73 2.22 1.17 2.22'' 1.14 1.00 - -- -1.18 Beozcne 0 1.58' Fertilizer and iasccticides 2.23. 1.42 1.44 -- - - -1.20 1.12 1.65. -- -3.07' 1.71 1.57 Viral hrpatilis Fomilyhistory of mslgnamy 1-55 1.35 1.55 1.63 0.GI 0.81 1.45 1.59 2.53, 1.15 1.78" - 3.00 4 . O V 1.67 0.67 1.47 1.02 '. 1 1, I 3 #I ___---_I--. -. ~ ._ m ------B --- ~ -_- ~ '\ ~ n ~, 1 . 1$7 ~ ?& 3 B ~ ~ ~ ~ ~ . R ; S ~($BB~*fit?J) ~ ~ ~ ~ ~ ~ ~ Table 3 ORs of the risk factors of l e u k e m i a s and aplastic an em in,^ ANLL M2a M3 M5 X-rv Chlxamphenical Antipyretics 1.22. 1.99. 1.u* Antirenmatics Benzene Fertilizer. insecticides Virnl hepatitis 1.a* 2.15, Family histony of malignancy 1.46." Other 1.62' ALL CML 1.73.* 1.87.. 2.89** \ CLL /AAA 2.42- CAA I 1.:t** 2.73. 1.96'. 6.87. A calculated with conditional logistic model for multiple variables 14 I ?*z1985; Jniversitp 3 1979: Blood rRisk Factors Analysis of Leukemia and Aplastic Anemia in China , 9 c g i n c s e g i d e m i o l o g i c 9 u d y Group of &/ Leukemia and Aplastic Y 4s -/ G a s e d o n the incidence survey of leukemia and aplastic anemia (AA) from 1986 to 1988, Case control studies (1257 new leukemia cases and 3 3 9 new AA cases) were carried out according to the type of leukemia and AA in order to beffer understand the epidesioloxic characteristics of t h e diseases. Controls mere matched randomly (age. sex and ethnic group) from t h e same population. ' The deta wYere analyzed w i t h the conditional Logistic multiregression model a n d e calculated on a n IBM-PC/XT. T h e risk factors of were found to be X-rays, autipyretics, benzene. pesticides and bimolane: that of. hI3 was :chIorc- amphenicol; that of M5 was X-rays: and t h a t of other ANLLs was pheoylbu- . tazone. The risk factors of ALL were -choloramphenicol, phenylbutazone a n d f i family members with cancer: those of CML were X-rays and hepatitis; those of C L L were chloramphenicol and benzene:those of AAA were antipyretics and Jhepatitis; and t h a t of CAA was X-rays Key words leukemia anemia, aplastic factor analysis, statisti-I corresponding author: Ynog Chongli, et a18 Iastitutz of Hernatohgyt Thnjia Countrywide Analysis of Risk Factors for Leukemia and Aplastic Anemia Narional Investigative Group for the Survey of Lcukcr~*iiaand Aplastic Anemia Synopsis The fouiidation of our study of Ieukeriiirt arid apiastic anemia i s a coniyarntivc survey using a 1:2 case ratio drawn from the entire population, surveyiiig the risk factors iu 1,257 cases of leukemia and 339 cases of aplastic anemia. Analyzing risk factors for leukemia and aplastic anemia types using conditional logistic\model analysis, dter accounting for extraneous factors, wc discovered risk factors associated with M2a include X-rays, antipyretic drugs, benzene type stibstanccs, arid insecticides arid chemical fertilizers. Bimolanc typc drugs is a high risk factor, Factors associated with M3 include chloramphenicol. Factors associated with M5 include X-rays. Factors associated with othcr fornis of acute non-lyinphatic letikcrnia (ANLLj include antircumatic type drugs. Factors associatcd with acute lymphatic leukemia (ALL) iiicludc chloramphenicol substances, antireumatics, and a family history of rnaligmncy . Factors associated with chronic myelocytic leukemia (CML) include X-rays and viral hepatitis. Faclors associated with nciitc aplastic anemia (AAA) iriciude antipyrelics and viral hepatiris. Factors associated with ciuonic aplastic ;;uicnua (CAA) iriclude X-rays. Single factor alalysis shows thnt significant factors associated with ckroilic lymphatic leukemia (CL,L) include chlormiptieiuccd and benzeric, ; Fey t e r m ~ C U ~ C I T U ~ Iaplastic ancnia si;ltis[irS;LI analysis of risk factors Lukcmia is a malignancy of the blood production system; aplastic anernia is a degradation of thc blood production system. Both illnesses are an equally 0Umve tlqeat to human health, Possible causes of these illnesses include four areas: physical, chemical, organic, and heredity. From 1986 to 1989, the National liivestigative. Group for the Study of Lmkenua and Aplastic Ancrnja conducted ~~eseitrc01b1 tho pathology arid risk factors of leukemic1 and aplastic anemia. The analysis of risk factors is presented bclow. Materids and Methods 1. Object of survey 1,257 cases of leukemia and 339 cases of aplastic anemia. All were ncw cases from each survey site during the period 1986 to 1988. Except for Beijing, Yanji in M n , and Shihezi in Xinjiang, due to condirions restricting comparative analysis, survey of risk factors was undcrtakcn at all 1 survcy sites. Each case was placed in a saniplc group according to age, sex, arid nationality, and then cornpared with "healthy individuals" who had never experienced blood disease or rnalignnncy and had been selwted at random. 2. Survey Method and Content All cases and comparisons uscd the same survcy qucsttiunnaire. Each iiivcsiigative site took rcsponsibility for thc survcy according to a singlc survey mcthod. The conten( of rhc survey included: general condition, environment, medical history, history of contacl with physical and cheirrical factors, medication history, family history, etc.. 3. Statistical Method All data was recorded on an IBM PC-XT using dBase-111. First we rmde an initial selection of risk factors by undertaking 3 process ofisolation and grouping of successive variables according to an analytical processing of conditions and hazards.' We [hen uscd a conditional logistic model to analyze single factors. Last, we undertook multiple factor logistic analysis using a progressive selection method.' Variables were selected by the test of comparative likciiess so as to obtain thc best n o n - s m m d iriodcl (Pq0.05; P<O,Ol). 4. Type Distribution Both I c L I ~ ~ J I I . ~a;n~d aplastic ancmia werc analyzcd accordin,s:to respective typcs. (ANLL secondary types M2a, M2b, M3, and M 6 were analyzed individually. Other ANLL secondary types, MI, M4, M6, and M7 had few cases and were combined for analysis.). II I NO. casci, No. 01 conrrol Table 1 T y p Dislribution ofCnscs Studied ANLL --.- ALL CML. CLL AAA CAA M2;1 G?b IvG M5 Others 193 12 171 178 2013 309 152 34 72 267 386 24 342 356 416 618 304 68 144 534 Res ul ts 1. Conditional Logistic Model for Monovariables Since there were too few cases of MZb, it's associated risk facrors wcre not discovered. X-ray, antipyretics, bimolam, bermnc, chemical fertilizer arid insecticides wcre related to M2a illness. Chioraniphenicol is related to M3. X-ray and anti reulnatics arc associated with MS. Chlorainphenicol is associated with othcr ANLL types. ChloraInphcnicol, antireurnafics, and fainily history of nxdignancy is associated wilh ALL, X-rays, antipyretics, bcnzcne, and viral hepatitis is asscxiatcd with CML. Chlor;rnipiienicol and krlzenc is associated with 2 CLL. Antipyre tics and viral hepatitis are associatcd with x u t c aplastic anemia (AAA). X-rays and benzene arc. associated with chronic aplastic anerrlja (CAB). - Ie- ---_ Tablc 2 OXs ol the k s k Factors of J-ruketniaand Aplastic hnerrLa* ANLL 1 . 0* 1.34 1.10 0.37" - 1.44 -- 1.55 0.8I 1+09 1.10 1.71** 1.28 1 . 9 ~1.52 1.07 ' 1.18 1.M* 1.64* 2.45* 1A3 2.73 2.22 1.20 1.12 -- c 1.45 1.59 1.15 1.78** u 1.23 2.m* 1.17 I ,oo - $.07* - 3 .oo 0.07 .93 2,13 2-.22** - 1.71 - 4.00" 1.47 1.82 1,37 1,14 1.18 - 1.57 r 1.67 1.02 2. Conditional Logistic Model for Multiple Variables Each type ot' leukemia and aplastic anemia, according to a process of progressive sclcction, wexe analyzed fox each risk factor using a conditional logistic rnodel for r.lluldple analysis, so as to find, the best non-saturatedmodel for each. After accounting for extraneous variwblcs, we discovered risk factors ; kssociated with M2a includc X-rays, antipyretic drugs, benzene type substances, and pesticides aid chemical fertilizers, Factors associated with M3 include C h l o f 9 r t ~ i ~ h ~ r i i C U !F.actors associated with MS include X-rays. Factors associated with other sccontiniy types of ANLL include antireumatics. Factors associated with ALL inchick chloramphenicol, antirerimatjcs, and a family history of malignancy. Factors associated with CML iwludr: X-rays and viral. hepatitis. Factors associttced M A iiicludc antipyretics a i d viral hepatitis. Factors associated with CAA include X-rays (Table 3), Cases of CLL were relatively few and niukiplc analysis fcv each fxtor yielded no statistically sigrrificant results. 3 1.62' 2.8P 2.73* I .%* 2.42** 6.87 Discussion Previous surveys of risk factors wcrc limited by the number of cascs, arid for the most parr did not analyze major causes of dit'fcrent types of leukemia and aplastic arierilia. This survey was carried uut on c? countrywide scale, with fi relatively largc ntitnber of cascs, and analyzed thc risk factors associated with the major typc.s of lcuke~niaand aplastic anemia. Surveys of inedical radiation tcchnieians, radiarion workers, and Japancsc atomic kmb survivors prove that leukemia and aplastic anemia i s a sidc-cffcct of ionized radiation .,'4s This survey further shows that ioiiized radiation is a major cause of M2a, bl5 arid CML myelocytic leukemias and chronic aplastic aiiciiia. Wc havc not yet discovered a clear relatioil between ionizcd radiation and lymphatic leukemia. 8imolatie type drugs are new drugs which in recent years havc klccn used to treat psoriasis. 1-iowcver, since it was introduced, the Chitme Journal of Hcnturolo~yhas received over 80 reports of this diu$ causing acutc myelocytic ; Icukemia (Ihostly M2a and M3): Laboratory observalions S ~ Q Wthat birnolmc is a strong chromosome abnormality inducer,' This siirvcy also discovered thal bimolslne is associated with M23, but since thc riitio of those who have used binlolane is relatively low, iiiultiple variable analysis is unable to confirm the relahiship betwren this drug and M2a, The aurhors belicvc that the many rcprts of illness, however, codirm a relationship t x ~ e e tbiinlolane and myelocytic lcukenlia, arid we have already recorntnended to the Ministry of Hcalth that rhe use of this drug be discontinued. The destructive effccis of chloramphenicol 011 bone fmn'ow is absolutely clair, Many shidics have all showed thar chlorarnplicrhd has strong lcukcmia arid aplastic anemia effects?" Sirice Japan restricted thc use of chloramphenicol in 1975, the death rate froin aplristic anemia has noticeably dccliiied.' This study discovered that chloraniphcriicol is a risk factor for M3 arid ALL. I I also has some reiatiunship wirli CLL. T I I ~cffcct on other types of Ieukenlirt rind aplastic anemia is unclear. Related studies i n China have chscoverd that therc is a defiriite relationship belwceri antipyretics arid aplastic anemia8 The results of ihis study also indicatc that antipyretics are associatcd with M2a and A A A . It is generally considered that antireumatics (most iinportantly ,4 I pheoy)butaz,enc) can cause acute Its rok as a cause of aplastic aiei7lia is not as apparent.' This study also did not discover a relationship between aritircuniatics and aplastic anemia, but this kind of drug has sonic reiatioiishup with ANLL and ALL. The destructive effect of benzene OrA the blood iiroduction system was c a d y established, Aksoy et a1 discovered that thc iociderice rare of leukcmia in Turkish beiizene 'workers was clearly higher than for. the general population.' Our research indicates that berxene has a strong cooperative relationship with MZa, arid somc rclationship with CML, CLL, and CAA. Surveys indicate that thc itdcience of leukenlia at oil ficIds is relatively high, sliowing that an e~ivironnleat coritamiriatcd with knzene and other chcinical. pollutants can cause leukemia. A r e i a h x h i p bctwecn insecticides and chcinic;d fertilizcrs, and leukemia and aplastic anemia has occasiotmlly been reported. This study indicates thcre is i:possiblc rctationship with M2a. We alicady know rhat viruses an caisc lcukcniia in scvcral animals such as chickens, clogs, and iiiicc.lo Adult T-cell leukemia i s caused by viral ii~cction. There is a relationship between Riirkitt's IyriipLiosarcorru and the EB virus, otiicr viruses can also cause iicutc degradation of blood production capability, and viral hepatitis c m lcad to acute aplastic anemia, The rcsults of this study indicate that there is a relationship betwecri vim1 hepatitis and both CML. and AAA, showing that therc is sonic cmperativc relationship bctwecii viral hepa'itis and lcukenria and aplastic merrlia. Previously, studics of fanliiics and twins indicaied that a portion of leukemia C ~ S C Sare influenced by heredity." Our study proves tha( there is a close 1I 1I relationship between ALL and a fariuly history of malignancy, showing that ALL has a relatively strang hereditary background. From the rcstilts of rhis study we can SCC that ~nyclocyticlei&icinia,cspxially M2a. is iiiore cIcwly affcctcd by e~ivironmentailrdlucnccs t ) m Iyrnphlic Icukcmia, ard hercditxy factors brtvc a close retationship with ALL. Due to the: limitations cJf retrospective. stildies anti tkc faci that the incubat iori periods for Ieukcmia and aplastic anemia arc s i l l iinclear, the rcsults of this study stiIl cannot indicatc the cause and effect relatiotiship betwecn risk factor; and leukcilia and aplastic atwmia, m d can only provide {cadsfor futurc: research on leiikcmia and aplastic rineniia pathology. -uI1------ 'Liu Y wiyuan, Expluiti~iliorfior lite iJse of Atralyticd Yroccwhg 01Cirtrcliiiorrs ard Hu:irrtD. Beijing: Scicncr Publishing, 1'336, pp. 19-35. z Y uSoiighn,et d," C o n d i h a l Logistic Rcgrcssm h h h i d s for Conipclrativs Resardi," C'hiirt?se LIiiIltJtirrf i r P m w i t i v e hledicitit~1985: 19 (5):292. 3Lincl h4S 'I'hc. Icuhemias: Epidemiologcx q x c t s . Nc\\ Y id.: Oxford Cmversit; I'rcss, 19x5 5 6