Document NGD1Z53BJp2kkV9gzXZ8OprXQ

Lr*rmir R a d Vd. 16, No. 6fl. pp. 62144.1992 Rimed L Grut Briuia. IS CIGARETTE SMOKING A RISK FACTOR FOR NON-HODGKIN'S LYMPHOMA OR MULTIPLE MYELOMA? RESULTS FROM THE LUTHERAN BROTHERHOOD COHORT STUDY MAR^ S. L m , *JOSEPH K. MCLAUGHLIN,A. NN W. HSING,'SHOLOMWACHOLDER,. HARVEYT. Co CHIEN,? LEONARD M. SCHUMAN,~ERIK BJELKEan~d WILLIAM J. BLOT' *Epidemiology & Biostatistics Program, National Cancer Institute, Rockville, MD 20892,U.S.A.; tWestat Inc., R o c W e , MD 20850,U.S.A.; $University of Minnesota, Minneapolis, MN 55455, U.S.A. and Kcnter for Epidemiologic Research, University of Bergen, Norway (Received 13 August 1991.Accepted 14November 1991) Abstract-Among 17633 U.S. white male insurance policy holders whose use of tobacco was characterized in a 1966 self-administered questionnaire, there were 49 deaths from non-Hodgkin's lymphoma (NHL) and 21 from multiple myeloma (MM) during a Byear follow-up. Men who had ever smoked cigarettes had an elevated mortality from NHL (RR = 2.1;CI = 0.949). with risk almost four-fold greater amongthe heaviestsmokers(RR= 3.8;CI 5: 1.4-10.1)compared with those who used no tobacco. In contrast, risk of Mh4 was only slightly elevated among those who had ever smoked Cigarettes (RR= 1.3; (=I = 0.4-3.9) and without evidence of a dosxesponse trend. S i this is the first cohort study suggesting a link between cigarettesmokingand NHL and findings from case-control studies have been inconsistent, additional clarification should be sought from larger incidence-based cohort investigations. Key w o r k Cigarette smoking, non-Hodgkin's lympholpa, multiple myeloma, prospective study, United states. I INTRODUClTON SINCE 1950, age-adjusted incidence rates for non- Hodgkin's lymphoma (NHL) and multiple myeloma 0have increased at l e p t two-fold in the U.S. [l].Although rates rose for males -and females in most age groups, increaseswere qost notable for the oldest groups, while plateaus or small declines have occurred in recent years among middle-age groups. Reason for these changes are largely unknown, although similar types of environmental factors (including ionizing radiation, solvents, pesticides, and other chemicals) have been postulated in the etiology of both lymphoproliferative malignancies [2,3]aswell as the leukemias 141. As evidence linking cigarette smoking with both myeloid [%lo] and lymphoid [6,7,11] leukemia has increased, the role of cigarette smoking in other hematolymphoproliferative cancers needs evaluation. An exam- ination of cigarette smoking and NHL and M M is Comaponderne to: Martha Linet,AS/BB/EBP/DCE, National Cancer Institute, Executive Plaza North Suite 415B. Rockville, MD 20892 U.S.A. presented here using data from a cohort study of 17633 American men. MATERIALS AND METHODS The methods of thisstudy have been d e s c r i i in detail elsewhere [12].EligibIe subjects were white male policy holders of the Lutheran Brotherhood Insurance Society. A mailedquestionnaire sent to membersaged35and older was completed by 68.5% of the subjects. Respondents differed little from non-respondents in age, urban/mral residence, policy status, and cancer mortality [13]. Information on tobaccouse,diet, and demographicbackground was collected in the questionnaire. Most study subjects resided in the upper midwest and northeast regions of the United States. Compared with the U.S. population, a higher proportion of subjectswere farmersfrom ruralareas and of Scandinavian heritage [14]. In 286 731 person-years of follow-up during 1%7-1986, there were 4513 deaths. Death certificates were coded for underlying and contributory causes of death by the nosologist of the Minnesota State Department of Health. Twenty-three percent of the cohort (4027subjects) were lost to follow-up due to lapsed policies or discontinuation of policies after premium maturity. The smokinghabits of these subjects did not differ from those remaining in the cohort. 621 . I --. 622 M.S. LINETer al TABLE 1. mSK OF DEATH FROM NON-HODGKIN'LSYMPHOMA AND MULTIPLE MYELOMA ASSOCIATED WITH CIGARElTE SMOKlNG HISTORY.LUTHERAN BROTHERHOOCODHORT, 196746 Non-Hodgkin's lymphoma Multiple myeloma Tobacco use* ~~~~~ Never any tobacco Any tobam, excluding cigarettes Ever cigarettes5 4 0 cigslday 11-20 cigs/day > mcie/day ( p for trend) No. person-years 58 888 21 680 190640 6357s 80230 43 268 RRt (95% CI) -1-.0- 1.1 (0.3-4.4) 2.1 (0.9-4.9) 1.0 (0.3-3.0) 2.3 (0.9-5.9) 3.8 (1.4-10.1) p <0.005 No. deaths4 6 3 38 7 17 13 RR (95% CI) -1-.0- 0.4 (0.1-3.8) 1.3 (0.63.9) 1.5 (0.4-5.2) 1.6 -(0.5--5.6) p = 0.70 No. deaths ~ 4 ~~ 1 14 7- 7 0 AU categories refer to ever users. t Adjusted for age. $ Missing data not included. 0 Includes current and ex-smokers. c A PoissonremessionDromam for modeling hazard func- DISCUSSION tioas was used co calculite&-adjusted relathe risks,with the hazardfunction assumed to be castant in each age interval [15,16]. Five-year age intervals were used, with relative risk calculated for each age stratum and summarizedover all strataforthe selectedvariables. Person-years, To our knowledge, this is the first cohort study to show a dose-response relationship between cigarette smoking and non-Hodgkin'slymphoma. In contrast, mortality from multiple myeloma was not notably were accumulatedup to death, loss to follow-up, or 1986. ?=.. increased among cigarette smokers nor assoCiated i4th amount smoked, although these findings are based on small numbers. i No significant excess of NHL, was found among RESULTS cigarette smokers in a cohort study of American male college students [5] nor was risk of combined There were 49 deaths from non-Hodgkin's lym- categories of hematolymphoproliferative neoplasms phoma and 21 from multiple myeloma during the 20- (NHL not separately considered) significantly elev- ! year follow-up. Risk of death from NHL or from MM did not vary significantly by level of education, ated among U.S.veterans [17]or British male physicians (181. Mortality from malignant lymphoma urban/rural status, occupation/iidustry, or place of (includingHodgkin'sdisease) was 38% higher among birth (data not shown). men aged 35-64, but not elevated among those aged Subjects who used any type of tobacco had an 65-79, who ever smoked compared with those who elevated risk of NHL (RR = 1.9; 95%CI =0.84.5) never regularly smoked in a follow-up s h d y of but little increase in M M (RR = 1.1; 95%CI = 0.4- American Cancer Societyvolunteers [191. Somecase- 3.3). When smokers were classified by number of control studies have reported an excess risk for NHL cigarettes smoked daily, a s t a t i s t i d y significant of 3040% among cigarette smokers, but none found dosMesponse pattern was observed for NHL,with a gradient with amount smoked (20-221. Other case- risk increasing to 3.8 among those smoking more than oae pack per day (Table 1). Risks were similar control investigations have found no association tu,241. for current and ex-smokers, although the numbers Multiple myeloma was not separately evaluated, of deaths were sparse (data not shown). Risk of but included in combined groupings of hemato- M M was increased by 30%among cigarette smokers, lymphoproliferative malignancies, in some earlier although there was no dose-response, and lower than cohort studies which showed no excess of these neo- expected among users of pipes and cigars only plasms among cigarette smokers [17,18]. In other (Table 1). cohort investigations of cancer Occurrence among Cigarette smoking 623 cigarette smokers, findings for M M were not shown jects to minimize the actual level of cigarettes smoked (even as part of combined group of hemato- daily. lymphoproliferative neoplasms) [S,191. Recently, In summary, our cohort study shows evidence sug- Mills et uf. reported a sigmficant increase and dose- gesting a causal link between cigarette smoking and response trend for multiple myeloma based on 9 ex- NHL.Findings do not support such an association smokers and 2 current smokers (11 myeloma cases for MM. Additional confirmation of our results is who had ever smoked cigarettes) in a six-year follow- needed. Cohort and casecontrol investigations with up of BOO0 U.S. Seventh Day Adventists [B]. No substantialnumbers of histologically verified incident excess of M M has been found in the 26-year follow- cases of NHL and M M would be helpful, particularly up 293 916 U.S.veterans (Heineman er ul..,personal if emphasis is given to subtype specification of NHL. communication). Case-control studies of multiple myeloma in both the U.S.[20,25,26] and Canada [27] have generally shown no associations, although REFERENCES a Swedish study reported an increased risk among former cigarette smokers [a]. 1.Devesa S. S., Silverman D. T., Young J. L., Pollack E. S., Brown C.C., Horm J. W., Percy C. L., Myers Incidence trends for NHL during the past several decades are consistent with an etiologic role for tobacco use. Incidence rose dramatically among the elderly, and to a lesser extent among middle-aged persons, with the rate of increase among the latter M.H., Mckay F. W. & Fraumeni J. F. Jr (1987)Cancer inadence and mortality trends among whites in the United States, 19474.1. nurn. Cuncer Imt. 79,701- no. 2. Greene M.H. (1982)Non-Hodgkin's lymphoma and mycosis fungoides. In Cancer Epidemiology and Pre- apparently peaking during the 1970s. vention (Schottenfeld D. & Fraumeni J. F. Jr, Eds). 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