Occupational and Environmental Medicine 1997;54:477-482

Laryngeal and hypopharyngeal cancer andoccupation: results of a case-control study

Paquerette Goldberg, Annette Leclerc, Daniele Luce, Jean-Frangois Morcet,Jacques Brugere

AbstractObjectives-To ascertain whether certainoccupations are associated with laryngealor hypopharyngeal cancer.Methods-A hospital based case-controlstudy was carried out in 15 hospitals inFrance. It included 528 male cases diag-nosed between January 1989 and April1991, and 305 male controls with variousother types of cancer. Interviews werecarried out to obtain lifetime job historiesand information on potential confound-ers. Logistic regression was used to com-pute the odds ratios (OR) for each ofabout 80 occupations and industries.Results-There was an excess risk oflaryngeal and hypopharyngeal canceramong service workers (OR 2.2, 95% con-fidence interval (95% CI) 1.3 to 3.9), agri-cultural and animal husbandry workers(OR 1.6, 95% CI 0.9 to 2.8), miners andquarrymen (OR 2.0, 95% CI 0.9 to 4.3),plumbers and pipe fitters (OR 2.6, 95% CI0.8 to 8.1), glass formers and potters (OR4.3, 95% CI 1.0 to 18), transport equip-ment operators (OR 1.5, 95% CI 1.0 to2.5), and unskilled workers (OR 1.7, 95%CI 1.0 to 2.9). Analysis by industrialbranch showed an excess risk for coalmining (OR 2.1, 95% CI 1.1 to 4.1), manu-facture ofmetal products (OR 1.9, 95% CI1.0 to 3.3), and administration and sani-tary services (OR 1.7, 95% CI 1.1 to 2.5).Conclusion-These results suggest thatoccupational exposure might have a rolein generating laryngeal and hypopharyn-geal cancer, and indicate the need for fur-ther evaluation of these findings, and forthe identification ofthe carcinogens whichmight account for the excess risks foundfor certain occupations.

(Occup Environ Med 1997;54:477-482)

Keywords: epidemiological study; occupational risk fac-tor; anatomical site

During the period from 1983 to 1987, theannual age standardized incidence of laryngealcancer among men varied from four to six per100 000 in most European countries, but wasas high as 12 per 100 000 in Italy and France.'For the hypopharynx, the age standardizedincidence in France (8.6 per 100 000 men-years) was higher than in the other Europeancountries,' where it varied from 0.7 to 1.2. Forthe white male population ofthe United States,the age standardized incidences from 1983 to

1987 were 6.8 and 1.5 respectively (for100 000 men-years) for cancer of the larynxand hypopharynx.Tobacco smoking and alcohol consumption

have been established as the main risk factorsfor laryngeal and hypopharyngeal cancers." Amulticentre study coordinated by the Inter-national Agency for Research on Cancer(IARC) in six populations of southern Europe4showed that the risk associated with a high levelof alcohol consumption (more than a litre ofwine a day or equivalent) rose about twofoldfor the larynx and about fourfold for thehypopharynx compared with the risk forsmaller consumers. In the same study, the con-sumption of more than 25 cigarettes a day wasassociated with a risk of laryngeal or hypopha-ryngeal cancer 16 times greater than the riskfor non-smokers. Comparable results havebeen established in other studies.5 8As the studies on occupational risk factors

for laryngeal cancer'-12 or pharyngeal cancer" 1have produced conflicting results, the existenceand magnitude of certain associations betweenthe risk factors studied and these diseases arestill questionable, as shown in a review of theepidemiological literature on the occupationalfactors for cancers of the upper respiratorytract.'5 The aim of the present analysis of acase-control study by job title was therefore toprovide additional information about theoccupational risk factors for laryngeal andpharyngeal cancer.

Subjects and methodsCases were male patients with primary malig-nancies of the hypopharynx and the larynxdiagnosed between 1 January 1989 and 30April 1991; for the hypopharynx, the caseswere collected over a shorter period, so thattheir number did not exceed half the totalnumber of cases collected. In all, 664 patients,all resident in France, were identified for studyin the 15 participating hospitals. However, 1 1of them (1.6%) died before an interview couldbe completed, 40 (6%) could not be inter-viewed for health reasons, 63 (9.5%) could notbe located, and 22 (3.3%) refused to partici-pate. Finally, therefore, 528 histologically con-firmed cases of squamous cell cancer wereincluded in the study. Of these, 300 affected thelarynx (196 the endolarynx, and 104 theepilarynx), 206 the hypopharynx, and 22 werecases of unspecified or synchronous cancers ofthe larynx and hypopharynx. The codingscheme for sites and subsites was that used byTuyns et at': the endolarynx includes thesupraglottis (international classification of

INSERM Unite 88, 14rue du Val d'Osne,94410 Saint-Maurice,FranceP GoldbergA LeclercD LuceJ-F Morcet

Institut Curie, 26 rued'Ulm, 75005 Paris,FranceJ Brugere

Correspondence to:Dr Paquerette Goldberg,INSERM Unite 88, HopitalNational de Saint-Maurice,14 rue du Val d'Osne, 94415Saint-Maurice Cedex,France.

Accepted 26 February 1997

477

on May 17, 2020 by guest. P

rotected by copyright.http://oem

.bmj.com

/O

ccup Environ M

ed: first published as 10.1136/oem.54.7.477 on 1 July 1997. D

ownloaded from

Goldberg, Leclerc, Luce, Morcet, Brugire

Table 1 Laryngeal and hypopharyngeal cancer andoccupation, France (1989-91) characteristics of cases andcontrols

Cases Controls

n (%) n (%/-)

Region:Lille 149 (28.2) 76 (24.9)Strasbourg 99 (18.8) 58 (19.0)Paris 96 (18.2) 68 (22.3)Bordeaux 80 (15.2) 46 (15.1)Nantes 68 (12.8) 33 (10.8)Caen 36 (6.8) 24 (7.9)

Age at diagnosis (y):<50 107 (20.3) 42 (13.8)50-59 190 (36.0) 88 (28.9)60-69 172 (32.6) 101 (33.1)70 59 (11.2) 74 (24.3)

Mean 58.0 60.7Level of education:

Primary 317 (60.0) 137 (44.9)Lower vocational 144 (27.3) 84 (27.5)Lower secondary 19 (3.6) 23 (7.5)Upper secondary 16 (3.0) 15 (4.9)Upper vocational 17 (3.2) 12 (3.9)University 15 (2.8) 33 (10.8)Other - 1 (0.3)

Tobacco smoking (pack-years):Data missing - (0.6) 1 (0.3)Non-smoker 15 (2.8) 82 (26.9)1-29 130 (24.4) 112 (36.7)30-45 138 (26.1) 61 (20.0)45 245 (46.0) 49 (16.1)

Alcohol consumption (glasses/day):Data missing, abstainers 24 (4.5) 9 (3.0)Occasional and 1-2 77 (14.8) 112 (36.7)3-4 80 (15.2) 61 (20.0)5-8 158 (29.8) 74 (24.3)9-12 109 (20.6) 31 (10.2)¢ 12 80 (15.2) 18 (5.9)

Total 528 305

diseases ninth revision (ICD-9) 161.1), glottis(ICD-9 161.0), subglottis (ICD-9 161.2), andendolarynx unspecified (ICD-9 161.8-9), theepilarynx includes the free border of theepiglottis (ICD-9 146.4), the posterior surfaceof the suprahyoid portion (ICD-9 161.1), thejunctional region of three folds (ICD-9 146.5),the aryepiglottic fold, the arytenoid andinterarytenoid incisure (ICD-9 161.1, 148.2),and the epilarynx unspecified (ICD-9 149.8,195.0), and the hypopharynx includes the piri-form sinus (ICD-9 148.1), the post-cricoidarea (ICD-9 148.0), the posterior wall (ICD-9148.3), and the hypopharynx unspecified(ICD-9 149.8).This study on laryngeal and hypopharyngeal

cancer was part of a larger one on the occupa-tional risks of cancer of the upper respiratorytract (sinonasal cavities, larynx, and hypophar-ynx). For practical reasons, controls wereselected during the 1987-91 period, andconsisted of patients in hospital selected to becomparable with the cases. Thus, controls weremale patients with primary cancer selected byfrequency matching for age, with a control tocase ratio of about 1: 1 for the larynx, and 3:2for the hypopharynx. To obtain comparablecatchment areas for cases and controls, thecontrols were patients with types of cancer

requiring the same medical environment as thecases. The hospital departments concernedwere specialised departments in the public or

semipublic sector, located in the same hospitalsas the cases, or in similar hospitals nearby. Allthe eligible controls were identified on the

admission lists ofthese departments as patientswithout previous treatment for the pathologythat caused the admission to hospital, withcharacteristics corresponding to the inclusioncriteria. Identification through hospital admis-sion lists had already been used by others,7 10and led here to the recruitment of 355 eligiblecontrols. However, 50 ofthem (14%) could notbe interviewed (14 for health reasons, 22 couldnot be located, and 14 refused), so that 305were actually included in the study.

Controls were patients with primary cancerof 15 sites: rectum or anal canal (n=30), liver orgall bladder (n= 15), pancreas (n=1 1), haemat-opoietic system (n=34), bones or cartilage(n=7), soft tissues (n=1 1), melanoma (n= 18),prostate (n=63), testis (n= 17), bladder (n=29),other urinary organs (n=27), brain or nervoussystem (n=18), thyroid (n=18), colon (n=5),and stomach (n=2).

Table 1 shows the regional distribution ofcontrols and cases. As the distribution wassimilar according to the region, adjustment forthis variable was considered unnecessary.

Personal interviews were conducted witheach subject. The questionnaire covered demo-graphic characteristics, detailed alcohol con-sumption, and tobacco smoking, and detailedlifetime occupational history, including jobtitles and description of tasks performed. Forthis history, a questionnaire close to that elabo-rated in Montreal by Gerin and Siemiatycki,'6was used, to collect detailed information on alljobs held for six months or longer. Thisquestionnaire had already been used in Frenchstudies. "

Jobs were coded according to the 1968international standard classification of occupa-tions (ISCO) of the international labourorganisation (ILO code 1968)18 and the indus-trial branches, according to the United Nationsinternational standard industrial classification(ISIC) code.' To obtain sufficient numbers foranalyses, jobs were grouped into 51 categoriesand industries into 44, largely on the basis ofthe subheadings.

Analyses were conducted for the larynx andhypopharynx together, with the same controlgroup, because of the contiguity of theseanatomical sites and the similarity of their mainrisk factors (alcohol and tobacco). Also, oddsratios (ORs) were computed for each of thethree subsites (endolarynx, epilarynx, andhypopharynx).Two kinds of occupational variable were

used for the analyses: having ever (v never)worked in a selected occupation, and havingever (v never) worked in a selected industry.For each occupation, the period of firstemployment, in two categories (until 1945, andas from 1946), was also analysed to find possi-ble differences between the risks of these peri-ods. Similarly, analyses were performed ac-cording to the duration of employment, intotwo classes (<9 years, and > 10 years), to findpossible dose-response effects. To allow for anyinduction and latency effects, analyses werealso performed after excluding all exposureduring the 10 years immediately precedingdiagnosis.

478

on May 17, 2020 by guest. P

rotected by copyright.http://oem

.bmj.com

/O

ccup Environ M

ed: first published as 10.1136/oem.54.7.477 on 1 July 1997. D

ownloaded from

Laryngeal and hypopharyngeal cancer and occupation

Table 2 Laryngeal and hypopharyngeal cancer and occupation, France (1989-91): odds ratios by job title

Cases Controls 5 ¶ILO code

J7ob title 68 n n OR (95% CI) OR (95% CI)

Professionals, technicians, managersAdministrative workersSales workersService workersFarmersAgricultural, animal husbandry workersForestry workers, fishermen, huntersProduction supervisorsMiners, quarrymenMetal processersWood preparation, paper workersChemical processersTextile workersFood, drink processing (not butchers,

bakers)ButchersBakersTailors, dressmakersShoes, leather goods makersCabinet makersStone cutters, carversBlacksmithsToolmakers, metal pattern makers, metal

markersMachine tool setter-operatorsMachine tool operatorsMetal grinders, polishers, tool sharpenersOther blacksmiths, toolmakers, machine

tool operator.Machine fitters, machine assemblersWatch clock precision instrument makersMotor vehicle mechanicsMachine fitters, assemblers (not electric)Electricians, electroniciansPlumbers, pipe fittersWelders, flame cuttersSheet metal workersStructural metal preparers, erectorsGlass formers, pottersRubber plastics product makersPrintersPaintersOther production and related workersBricklayers, stonemasonsReinforced concreters, cement finishersRoofersCarpenters, joiners, parquetry workersPlasterersOther construction workersStationary engine operatorsDockers, freight handlersOther material handling and dockersTransport equipment operatorsUnskilled workers

* P<0.05; t 0.05<P< 0.10; * controls n = 0; § ajusted for age, drinking, smoking; ¶ and education.

Analyses were conducted with multivariatelogistic regressions, and variables were calcu-lated with EGRET software20 with adjustmentsfor age, drinking, smoking, and with and with-out adjustment for level of education. To avoidtoo small numbers, the analyses according tothe period of first employment and theduration of employment were conducted withadjustment for age only. Age was categorised as

a four class variable (<50 years, 50-59, 60-69,and 70 years), smoking, as a four classvariable (non-smoker, <30, 30 to <45, and3e45 pack-years), drinking, as a five class vari-able, in number of glasses of alcoholic beverageconsumed daily (occasional drinker or one to

two glasses, 3-4, 5-8, 9-12, and > 13 glasses),and level of education, as a two class variable(primary level or less, more than primarylevel). Non-respondents for alcohol (n=5) andtotal abstainers (n=28) were excluded from theanalysis. Indeed, the category of non-drinkerscomprised former heavy drinkers who eventu-

ally stopped drinking alcoholic beverages due

to their health. As in other studies,'0 12 ORs

were not calculated when the number ofexposed subjects (cases plus controls) was lessthan five.

ResultsThe main characteristics of the sample (table1) indicate that the cases were slightly youngerand less educated than the controls: thus, 60%of the cases had only primary education but44.9% of the controls. More cases thancontrols were smokers and drinkers, withhigher levels of consumption.

Table 2 shows, according to job title, thenumber of cases and controls, and the ORs and95% confidence intervals (95% GIs), calcu-lated with and without adjustment for educa-tion, for all sites combined. High ORs, signifi-cance at P<0.05, or borderline significance at

0.05<P<0. 10, were found for service workers,agricultural and animal husbandry workers,miners and quarrymen, plumbers and pipe fit-

Oxx to 2xx3xx4xx5xx60x to 61x62x63x to 64x70x71x72x73x74x75x

77x77377679x80x81x82x831

832833834835

83984184284384985x87187287387489x90x92x93x94x951952953954955956 to 95996x971972 to 97998x99x

5590549055681713372391023

17202267

17418

99

186

16313

2726272224186

1356

249

55145

367

237

2517

118104

6980392649278

121313847

61111477

2

4682

10183

16181658

10

448

113

1625

11

81

258

3728

0.5*0.7t0.82.2*0.71.6t0.90.72.Ot0.90.41.31.9

1.80.91.31.30.61.02.93.5

1.21.20.71.7

1.01.00.71.10.71.12.51.81.1

4.3*0.60.3t1.20.91.62.50.41.5

1.23.40.3*0.71.5t1.7*

(0.3 to 0.7)(0.4 to 1.0)(0.5 to 1.4)(1.3 to 3.9)(0.4 to 1.1)(0.9 to 2.8)(0.3 to 2.3)(0.3 to 1.8)(0.9 to 4.3)(0.4 to 1.9)(0.1 to 1.3)(0.4 to 5.1)(0.7 to 5.0)

(0.6 to 5.7)(0.4 to 2.3)(0.5 to 3.0)(0.2 to 7.4)(0.2 to 2.4)(0.4 to 2.6)(0.3 to 31)(0.8 to 16)

(0.3 to 4.5)(0.4 to 3.9)(0.3 to 1.7)(0.2 to 12)

(0.4 to 2.5)(0.5 to 2.1)(0.1 to 3.9)(0.5 to 2.4)(0.3 to 1.4)(0.5 to 2.5)(0.8 to 7.6)(0.7 to 4.6)(0.4 to 3.0)(0.7)(1.0 to 18)(0.1 to 3.5)(0.1 to 1.1)(0.5 to 2.8)(0.2 to 3.7)(0.8 to 3.1)(0.5 to 11)(0.1 to 1.9)(0.7 to 3.3)(0.8)(0.5 to 2.9)(0.4 to 30)(0.1 to 0.6)(0.3 to 1.8)(1.0 to 2.5)(1.0 to 2.9)

0.5*0.7t0.92.2*0.6*1.40.80.81.80.80.41.51.6

1.90.91.21.20.61.12.53.1

1.51.20.81.4

0.91.00.71.20.71.22.6t1.91.2

3.7t0.60.3t1.10.91.42.50.41.5

1.23.80.3*0.61.41.6t

(0.3 to 0.8)(0.5 to 1.1)(0.5 to 1.5)(1.3 to 3.9)(0.3 to 1.0)(0.8 to 2.4)(0.3 to 2.0)(0.3 to 2.1)(0.9 to 3.9)(0.4 to 1.7)(0. 1 to 1 .2)(0.4 to 5.8)(0.6 to 4.5)

(0.6 to 6.0)(0.4 to 2.2)(0.5 to 3.1)(0.2 to 7.1)(0.2 to 2.3)(0.4 to 2.8)(0.2 to 26)(0.7 to 14)

(0.4 to 5.5)(0.4 to 4.1)(0.3 to 1.9)(0.2 to 9.6)

(0.4 to 2.4)(0.5 to 2.2)(0.1 to 3.7)(0.5 to 2.5)(0.3 to 1.5)(0.6 to 2.7)(0.8 to 8.1)(0.7 to 5.0)(0.4 to 3.1)(0.7)(0.9 to 15)(0.1 to 3.4)(0.1 to 1.2)(0.5 to 2.7)(0.2 to 3.7)(0.7 to 2.7)(0.5 to 12)(0.1 to 1.7)(0.7 to 3.2)(0.8)(0.4 to 2.7)(0.4 to 35)(0.1 to 0.5)(0.2 to 1.7)(0.9 to 2.3)(0.9 to 2.6)

479

on May 17, 2020 by guest. P

rotected by copyright.http://oem

.bmj.com

/O

ccup Environ M

ed: first published as 10.1136/oem.54.7.477 on 1 July 1997. D

ownloaded from

Goldberg, Leclerc, Luce, Morcet, Brugire

Table 3 Laryngeal and hypopharyngeal cancer and occupation, France (1989-91): odds ratios by industrial branch

Cases Controls (P (¶)

Industrial branch ISIC code n1 n OR (95% CI) OR (95% CI)

AgricultureCoal miningOther miningManufacture of food (not bakery, alcohol)Manufacture of bakery productsAlcohol industriesSpinning, weaving, finishing textilesManufacture of textile (not spinning,

weaving)Manufacture of leather footwear and repair

Sawmills, wood millsManufacture of wood (not sawmills)Manufacture of paperPrinting, publishingManufacture of chemical product (not

fertilisers)Manufacture of fertilisers, pesticidesManufacture of petroleum, coal productsManufacture of rubber, plastic productsManufacture of pottery, earthenware, glass,

mineralsBasic metal industriesManufacture of metal productsManufacture of machinery (not electrical)Manufacture of electrical machineryShip buildingManufacture of transport equipment (not

shipbuilding)Other manufacturing industriesElectricity, gas, waterConstructionTradeRestaurants, hotelsRailway transportationRoad transportationOther transportationCommunicationsFinancing, real estate servicesAdministration, sanitary services

Education, scientific institutesMedical servicesSocial services

Recreational services

Repair (not leather, vehicles)Repair of motor vehiclesLaundry, cleaningDomestic services

Barber, beauty shops

l lx to 13x 13221x 4722x to 29x 731x 423117 263131 to 3133 143211 31

32x 8323 324 9511 83311 3033x 22341 11342 13

351 352 193512 3353 354 4355 356 10

36x 2537x 39381 64382 54383 133841 11

384 40385 to 390 134xx 75xx 16161x 62x 6463x 347111 307112 to 7114 317116 to 7191 1672x 48xx 4291x 92x 96x 169931 932 21933 13934 to 939 594x 79512 9514 9519 79513 21952 8953 69591 5

* P<0.05; t 0.05<P< 0.10; t controls n = 0; § adjusted for age, drinking, smoking; ¶ and education.

ters, glass formers, and potters (based on 13cases and four controls), transport equipmentoperators, and unskilled workers. The calcula-tions with or without adjustment foreducational led to similar results. For otheroccupational groups, mainly professional, tech-nical, and administrative workers, printers, anddockers and freight handlers, ORs were signifi-cantly lower than unity or borderline.

In the analyses by anatomical subsite (resultsnot shown), an excess risk of cancer was alsofound among blacksmiths for the endolarynx(OR 4.6, based on nine cases and twocontrols); among toolmakers, metal patternmakers, and metal markers (OR 4.1, based on

four cases and four controls) for the epilarynx;and (except for butchers and bakers) among

food and beverage processers (OR 4.0) andbricklayers and stonemasons (OR 3. 1), for thehypopharynx.The results according to the period of first

employment (not shown) showed a significanthigh risk for the more recent period (1946-80),among service workers, agricultural and animalhusbandry workers, miners and quarrymen,

plumbers and pipe fitters, painters, and brick-layers and stonemasons. There was an excess

risk for both periods among transport equip-ment operators and unskilled workers.The ORs were only slightly modified whenallowance was made for a 10 year latencyperiod.When the data were analysed by duration of

employment (results not shown), significantlyhigh or borderline ORs were found for serviceworkers, transport equipment operators, andfor unskilled workers irrespective of the dura-tion. For miners and quarrymen, there was an

excess only in those employed for 10 years or

more.

Table 3 shows the associations resulting fromdata analysis according to industrial branch,calculated with and without adjustment foreducation: significant or borderline excess riskswere found for coal mining, manufacture ofmetal products, and public administration andsanitary services. For the activities of trade,communication, and education, ORs were

lower than unity.

DiscussionAn essential point in a case-control study isthat the people selected as controls should havesimilar past potential exposure as the cases. In

72161015121015

121117728

6337

1316232285

3056

67448

121187

3173291365416

23

1.22.1*0.41.51.41.11.2

0.40.90.81.72.40.6

2.30.50.40.8

1.31.51.9*1.30.80.9

0.81.71.01.30.6t1.91.31.00.80.2*0.61.7*0.4*0.60.70.41.10.9

2.13.3

(0.8 to 1.7)(1.1 to 4.1)(0.1 to 1.4)(0.8 to 3.0)(0.6 to 3.2)(0.4 to 3.1)(0.5 to 2.4)

(0.1 to 1.2)(0.3 to 2.8)(0.4 to 1.6)(0.7 to 4.5)(0.5 to 12)(0.2 to 1.7)

(0.8 to 7.1)(0.1 to 2.8)(0.1 to 2.1)(0.2 to 2.5)

(0.6 to 2.9)(0.7 to 2.9)(1.0 to 3.3)(0.7 to 2.3)(0.3 to 2.2)(0.3 to 2.8)

(0.4 to 1.5)(0.5 to 5.7)(0.3 to 3.3)(0.9 to 1.9)(0.4 to 1.1)(0.8 to 4.9)(0.6 to 3.0)(0.5 to 2.2)(0.3 to 2.3)(0.1 to 0.9)(0.3 to 1. 1)(1.1 to 2.5)(0.2 to 0.8)(0.2 to 1.5)(0.2 to 2.7)(0.1 to 1.8)(0.2 to 4.5)(0.4 to 2.0)(1.0)(0.3 to 14)(0.6 to 18)

1.02.0*0.41.51.51.01.0

0.40.90.71.72.40.6

2.50.50.40.8

1.11.41.9*1.40.80.9

0.81.91.01.20.6t2.01.41.00.80.22t0.71.7*0.5*0.70.60.41.00.9

1.83.4

(0.6 to 1.5)(1.0 to 3.8)(0.1 to 1.3)(0.7 to 3.0)(0.6 to 3.4)(0.3 to 3.1)(0.5 to 2.2)

(0.1 to 1.2)(0.3 to 2.7)(0.4 to 1.5)(0.6 to 4.4)(0.5 to 12)(0.2 to 1.7)

(0.8 to 7.7)(0.1 to 2.8)(0.1 to 2.2)(0.2 to 2.6)

(0.5 to 2.6)(0.7 to 2.8)(1.1 to 3.4)(0.7 to 2.5)(0.3 to 2.4)(0.3 to 3.0)

(0.5 to 1.5)(0.5 to 6.5)(0.3 to 3.5)(0.8 to 1.8)(0.4 to 1.1)(0.8 to 5.0)(0.6 to 3.1)(0.4 to 2.1)(0.3 to 2.2)(0.1 to 1.0)(0.4 to 1.3)(1.2 to 2.5)(0.2 to 1.0)(0.3 to 1.7)(0.1 to 2.5)(0.1 to 1.8)(0.2 to 4.3)(0.4 to 2.0)(1.0)(0.3 to 12)(0.6 to 20)

480

on May 17, 2020 by guest. P

rotected by copyright.http://oem

.bmj.com

/O

ccup Environ M

ed: first published as 10.1136/oem.54.7.477 on 1 July 1997. D

ownloaded from

Laryngeal and hypopharyngeal cancer and occupation

a study based on patients in hospital, a biascould arise if the reasons for being in hospital inthe public or semipublic sector departmentsselected for recruitment were not similar forcases and controls. In France, most cases ofcancer ofthe larynx or hypopharynx are treatedin such departments. The choice of the hospi-tal in a given area mainly depends on medicalcriteria. For this reason, the list of cancer sitesfor the present controls was established in sucha way as to ensure that cases and controls hadcomparable medical environments needed fortreatment. Hence the choice of participatinghospital services was unlikely to have been asource of bias.The fact that the controls were recruited over

a longer period than the cases might have led toa bias. However, when the controls selectedduring the periods 1987-8 and 1989-91 werecompared, their main characteristics werefound to be similar.Another problem in such a study is the ques-

tion of multiple comparisons, which maygenerate significant associations which occurby chance, independently of any associationbetween exposure and disease. For this reason,each result requires careful examination andevaluation of its relevance2" in the light of theresults of previous studies and of the knowl-edge available about both dose-response pat-terns and induction time.

Comparisons with the results of previousinvestigations by others were complicated,because different authors used different waysof classifying the occupations, industrialbranches, and anatomical sites consideredhere. The results previously reported for theoccupational risks of laryngeal and pharyngealcancer mostly concerned the endolarynx, whichwas sometimes subdivided into the glottis andsupraglottis." 22 23 However, the investigationson the pharynx did not distinguish between thehypopharynx and oro- pharynx.'3 14 24 Also, thediscrepancies between the results reportedmight have occurred because of statisticalimprecision due to sparse data.

Previous authors found a moderate excessrisk for the agricultural job categories' 10 12 13and it is therefore of interest to note that wefound an increased risk among agricultural andanimal husbandry workers, but not amongfarm managers and farmers. This differencemight be due to higher levels and longer dura-tions of exposure to a set of occupational orsocial risk factors for agricultural and animalhusbandry workers.The occupations involved in metal process-

ing and manufacture have already been consid-ered in different studies, including those ofmetal processor,9 metal grinder,'" and metalworking machine operator.'2 In the presentstudy, the OR for the basic metal industry wasmoderate (table 3), whereas the excess risk formetal product manufacturing was 1.9. Workersin these industrial branches with an excess riskwere blacksmiths (OR 4.6 for the endolarynx),and toolmakers, metal pattern makers, andmetal markers (OR 4.1 for the epilarynx), withhigher ORs for 10 years or more of employ-ment. In these branches, potential exposure to

several substances, including metals in general,specific metals, metal dust, cutting oils,and sulphuric acid, had already beenstudied.9 10 12 22 23 27 28 No strong evidence oftheir association with laryngeal cancer wasshown, but as the results of several studies wereconcordant for these branches, it would be ofinterest to continue analysing the specific typesof exposure they involve.Plumbers and pipe fitters, previously found

to be at risk of laryngeal cancer9 12 with anexcess risk when education was controlled for,as well as welders and flame cutters with amoderate OR of 1.8, might have been exposedto some of the same substances as workers inmetal industries as well as specific exposure tometal fumes.Although the role of asbestos in laryngeal

cancer is still controversial25 26 the excess riskfound here for bricklayers and stonemasons(OR 3.1 for the hypopharynx) might be due toexposure to asbestos. Asbestos might also be apotential risk factor for plumbers and otherworkers in the construction industry, in whichasbestos was much used. In several studies, theoccupations relating to this industry showedassociations with laryngeal cancer5 10-12 andpharyngeal cancer.'4 24

Contrary to previous studies, we found norisk for motor vehicle mechanics" 12 working inautomobile construction or the repair industry,in which the role of machining fluids (cutting,soluble, and synthetic oils) had beeninvestigated.27 28

The present result for miners and quarry-men is consistent with the results reportedelsewhere for mining occupations,24 and so isthe result for glass formers and potters.29 Bothcategories were exposed to silica, which hasalready been considered a possible risk factorfor laryngeal cancer.24

In agreement with other studies7 " in whichan excess risk was found for diesel oil andgasoline fumes, we found an excess risk fortransport equipment operators.On the basis of the present results, it would

be worth attempting to explain the excess riskswe found, by extending the analysis to includethe potential workplace carcinogens, which arestill under investigation for their role inlaryngeal and pharyngeal cancer.

This study was made possible by the support of the followinghospital departments: Service ORL (Ear, Nose, Throat), CHR,Lille (Pr Piquet, Dr Chevalier); Service ORL, Centre OscarLambret, Lille (Dr Lefebvre); Service ORL, CHR H6pital B,Lille (Pr Desaulty); Service ORL, H6pital des Enfants,Bordeaux (Pr Traissac); Centre Hospitalier Pellegrin-Tripode,Bordeaux (Dr Stoll); Service ORL, Fondation Bergonie,Bordeaux (Dr Renaud-Salis, Dr Faucher); H6pital Haut-Leveque, Pessac (Pr Amouretti, Pr Couzigou); Service ORL,CHR, Strasbourg (Pr Conraux); Service de Radiotherapie,Centre Paul Strauss, Strasbourg (Dr Jung); Service ORL, H6pi-tal de Hautepierre, Strasbourg (Pr Klotz); Service ORL, InstitutCurie, Paris (Dr Brugere); Service ORL, H6tel Dieu, Nantes(Pr Beauvillain); Service de Radiotherapie, Centre Rene Gaud-ucheau, St Herblain, Nantes (Dr Peuvrel); Service ORL, CentreFranqois Baclesse, Caen (Dr Blanchet); Service de Radi-otherapie, Centre Frangois Baclesse, Caen (Dr Couet).Interviews were conducted by B Agullo, J Allio, S Boulanger, JJChak, N Contour, G Mamane, S Pueyo, B Weber, P Zagury.Association pour la Recherche contre le Cancer (ARC), ComiteDepartemental du Val d'Oise de la Ligue Nationale contre leCancer, Ministere de la Recherche et de la Technologie.

481

on May 17, 2020 by guest. P

rotected by copyright.http://oem

.bmj.com

/O

ccup Environ M

ed: first published as 10.1136/oem.54.7.477 on 1 July 1997. D

ownloaded from

Goldberg, Leclerc, Luce, Morcet, Brugere

1 Parkin DM, Muir CS, Whelan SL, Gao YT, Ferlay J, PowellJ. Cancer incidence in five continents. Vol VI. Lyon: IARC,1992.

2 International Agency for Research on Cancer. IARC mono-graphs on the evaluation of carcinogenic risks to humans: alco-hol drinking. Vol 44. Lyon: IARC, 1988.

3 International Agency for Research on Cancer. IARC mono-graphs on the evaluation of carcinogenic risks of chemicals tohumans: tobacco smoking. Vol 38. Lyon: IARC, 1986.

4 Tuyns AJ, Esteve J, Raymond L, Berrino F, Benhamou E,Blanchet F, et al. Cancer of the larynx/hypopharynx,tobacco and alcohol: IARC international case-controlstudy in Turin and Varese (Italy), Zaragoza and Navarra(Spain), Geneva (Switzerland), and Calvados (France). Int_7 Cancer 1988;41:483-91.

5 Gubnel P. Chastang JF, Luce D, Leclerc A, Brughre J. Astudy of the interaction of alcohol drinking and tobaccosmoking among French cases of laryngeal cancer. 7 Epide-miol Community Health 1988;42:350-4.

6 Blot WJ. Alcohol and cancer. Cancer Res 1992;52:S2119-23.

7 Ahrens W, Jockel KH, Patzak W, Elsner G. Alcohol,smoking, and occupational factors in cancer of the larynx:a case-control study. Am . Ind Med 1991;20:477-93.

8 Zheng W, Blot Wj, Shu XO, Gao YT, Ji BT, Ziegler RG,Fraumeni JF. Diet and other risk factors for laryngeal can-cer in Shanghai, China. Am j Epidemiol 1992;136:178-91.

9 Burch JD, Howe GR, Miller AB, Semenciw R. Tobacco,alcohol, asbestos, and nickel in the etiology of cancer of thelarynx: a case-control study. _7 Natl Cancer Inst 1981;67:1219-24.

10 Zagraniski RT, Kelsey JL, Walter SD. Occupational risk fac-tors for laryngeal carcinoma: Connecticut, 1975-80. Am JEpidemiol 1986;124:67-76.

11 Muscat JE, Wynder EL. Tobacco, alcohol, asbestos, andoccupational risk factors for laryngeal cancer. Cancer 1992;69:2244-51.

12 Wortley P, Vaughan TL, Davis S, Morgan MS, Thomas DB.A case-control study of occupational risk factors for laryn-geal cancer. BrJt Ind Med 1992;49:837-44.

13 Huebner WW, Schoenberg JB, Kelsey JL, Wilcox HB,McLaughlin JK, Greenberg RS, et al. Oral and pharyngealcancer and occupation: a case-control study. Epidemiology1992;3:300-9.

14 Maier H, Fisher G, Sennewald E, Heller WD. BeruflicheRisikofaktoren fuir Rachenkrebs. HNO 1994;42:530-40.

15 Berrino F. Occupational factors of upper respiratory tractcancers. In: Hirsch A, Goldberg M, Martin JP, Masse R,eds. Prevention of respiratory diseases. Lung biology in healthand disease 68. New York: M Dekker, 1993:81-96.

16 Grin M, Siemiatycki J. The occupational questionnaire inretrospective epidemiologic studies: recent approaches incommunity-based studies. Appl Occup Environ Hyg 1991 ;6:495-501.

17 Luce D, Leclerc A, Morcet JF, Casal-Lareo A, Gerin M,Brugere J, et al. Occupational risk factors for sinonasalcancer: a case-control study in France. Anm 7 Ind Med1992;21:163-75.

18 International Labour Office. International standardclassification of occupations. Revised 1968. Geneva: BIT,1969.

19 Statistical Office of the United Nations. International stand-ard industrial classification of all economic activities.New-York: United Nations, 1968. (Statistical papers series M,number 4, revision 2.)

20 EGRET. Reference manual. Seattle: Statistics and Epidemiol-ogy Research Corporation 1985, 1989.

21 Savitz DA, Olshan AF. Multiple comparisons and relatedissues in the interpretation of epidemiologic data. Am 7Epidemiol 1995;142:904-8.

22 Soskolne CL, Jhangri GS, Siemiatycki J, Lakhani R, DewarR, Burch JD, et al. Occupational exposure to sulfuric acid inSouthern Ontario, Canada, in association with laryngealcancer. Scandj7 Work Environ Health 1992;18:225-32.

23 Maier H, Gewelke U, Dietz A, Thamm H, Heller WD, Wei-dauer H. Kehlkopfkarzinom und Berufstatigkeit Ergeb-nisse der Heidelberger Kehlkopfkrebsstudie. HNO 1992;40:44-51.

24 Haguenoer JM, Cordier S, Morel C, Lefebvre JL, Hemon D.Occupational risk factors for upper respiratory tract andupper digestive tract cancers. Br.7Ind Med 1990;47:380-3.

25 Smith AH, Handley MA, Wood R. Epidemiologicalevidence indicates asbestos causes laryngeal cancer. .Occup Med 1990;32:499-507.

26 Piolatto G, Negri E, La Vecchia C, Pira E, Decarli A, Peto J.An update of cancer mortality among chrysotile asbestosminers in Balangero, nothern Italy. Br.7 Ind Med 1990;47:810-4.

27 Eisen EA, Tolbert PE, Monson RR, Smith TJ. Mortalitystudies of machining fluid exposure in the automobileindustry I: a standardized mortality ratio analysis. Am .7 IndMed 1992;22:809-24.

28 Eisen EA, Tolbert PE, Hallock MF, Monson RR, Smith TJ,Woskie SR. Mortality studies of machining fluid exposurein the automobile industry III: a case-control study of lar-ynx cancer. Am j Ind Med 1994;26:185-202.

29 Guknel P, Engholm G, Lynge E. Laryngeal cancer inDenmark: a nationwide longitudinal study based on regis-ter linkage data. Br7 Ind Med 1990;47:473-9.

482

on May 17, 2020 by guest. P

rotected by copyright.http://oem

.bmj.com

/O

ccup Environ M

ed: first published as 10.1136/oem.54.7.477 on 1 July 1997. D

ownloaded from