a case-control study of wood dust exposure,...

50/. 4, 583-588, Sepiem/er /995 Cancer Epidemiology, Biomarkers & Prevention 583

A Case-Control Study of Wood Dust Exposure, Mutagen Sensitivity,

and Lung Cancer Risk’

Xifeng Wu,2 George L. Delclos, John F. Annegers,Melissa L. Bondy, Susan E. Honn, Betty Henry,T. C. Hsu, and Margaret R. Spitz3

Departments of Epidemiology IX. W.. M. L. B.. S. E. H.. B. H.. M. R. S.l and

Cell Biology IT. C. HI. The University of Texas M. D. Anderson Cancer

Center. and The University of Texas School of Public Health 1G. L. D..

J. F. Al. Houston. Texas 77030

Abstract

The associations between lung cancer risk, mutagensensitivity (a marker of cancer susceptibility), and aputative lung carcinogen, wood dust, were assessed in ahospital-based case-control study. There were 113African-American and 67 Mexican-American cases withnewly diagnosed, previously untreated lung cancer and270 controls, frequency-matched on age, ethnicity, andsex. Mutagen sensitivity ( 1 chromatid break/cell aftershort-term bleomycin treatment) was associated withstatistically significant elevated risk for lung cancer [oddsratio (OR) = 4.3; 95% confidence intervals (CI) 2.3-7.91. Wood dust exposure was also a significant predictorof risk (overall OR 3.5; CI 1.4-8.6) after controllingfor smoking and mutagen sensitivity. When stratified byethnicity, wood dust exposure was a significant riskfactor for African-Americans (OR 5.5; CI 1.6-18.9)but not for Mexican-Americans (OR 2.0; CI 0.5-

8.1). The ORs were 3.8 and 4.8 for non-small cell lungcancer in Mexican-Americans and African-Americans,respectively, but were only statistically significant forAfrican-Americans (CI 1.2-18.5). Stratified analysissuggested evidence of strong interactions between wooddust exposure and both mutagen sensitivity and smokingin lung cancer risk.

Introduction

Lung cancer is the paradigm of an environmentally induceddisease. However, only a fraction of exposed individuals will

develop the disease. Genetically determined modulation of en-vironmental exposure is an attractive mechanism to explain the

variation in host susceptibility ( 1 ). Hsu has hypothesized inter-

individual differences in susceptibility to mutagenesis, based on

an in vitro assay. quantificating the number of bleomycin-

induced chromatid breaks in short-term. cultured peripheral

lymphocytes (2). Previously. we have demonstrated that

Received 3/14/95: revised 5/3 1/95: accepted 6/2/95.

� This work was supported by grant CA 55769.2 In partial fultlllment of the requirements for the doctoral degree at The

University of Texas Schml of Public Health. Houston. TX.

, To whom requests for reprints should be addressed, at Department of Epide-

miology. Box I 89, The University of Texas M. D. Anderson Cancer Center,1515 Holcombe Boulevard, Houston. TX 77030.

mutagen sensitivity was a significant predictor of multiple

primary cancer risk after an initial head and neck cancer (3).Our data from this study and previous studies have alsoshown that mutagen sensitivity is an independent risk factor

for lung and upper aerodigestive tract cancers after control-ling for the effects of tobacco and alcohol (4-6).

Although tobacco exposure is the overwhelming environ-mental determinant of lung cancer. occupational factors havealso been implicated in lung-cancer risk. In particular. it isbiologically plausible that exposure to inhaled dusts (with or

without concomitant cigarette smoking) has an etiological role

in lung cancer. Exposure to wood dust occurs worldwide be-

cause of the traditional use of wood for fuel and as construction

material. The association of wood dust with adenocarcinoma of

the nose and paranasal sinuses has been convincingly demon-

strated (7-11). Because the tracheobronchial mucosa is similarto the mucosa lining the sinuses. the link between bronchialcarcinoma and wood dust exposure has been evaluated but withinconsistent results ( I 2-I 7). The use of a variety of potentially

carcinogenic chemicals to preserve, manufacture, and finish

wood products might also be implicated in the adverse effect of

such exposure (18).This present report of tobacco and wood dust exposures is

based on data from a case-control study of lung cancer incor-porating epidemiological data with a panel of susceptibilitymarkers. Because of the data cited above, wood dust exposurewas selected a priori for this occupational analysis. The pur-

pose of this analysis was to evaluate wood dust exposure as apotential lung carcinogen, to assess the interactive effects ofmutagen sensitivity and cigarette smoking on lung cancer risk,

and to test the hypothesis that cancer risk was increased inindividuals who have a susceptible genetic trait and a relevant

carcinogenic exposure.

Materials and Methods

Study Subjects. The cases and controls included in this report

are from an ongoing molecular epidemiological study of lungcancer in minority populations (African- and Mexican-Amen-

cans). The 180 cases had newly diagnosed. histologically con-

firmed lung cancer. had not been treated previously with ra-diotherapy or chemotherapy, and reported themselves as being

of African-American (n = I 1 3) or Mexican-American (n = 67)

ancestry. The cases were recruited from The University ofTexas M. D. Anderson Cancer Center; from county. commu-nity. and Veterans Administration hospitals in the Houston

metropolitan area; and from community hospitals in San An-tonio, TX. There were no age, histological, or stage restrictions.

The controls were 134 African-American and 136 Mexican-American healthy individuals without prior histories of cancerwho were recruited from community centers, cancer screeningprograms, churches. and employee groups in both Houston and

San Antonio and then frequency-matched to the cases by age,ethnicity. and sex.

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584 WOOd Dust. Mutagen Sensitivity, and Lung Cancer

4 The abbreviations used are: DOT. Dictionary of Occupational Titles: NSCLC,non-small cell lung carcinoma: OR. odds ratio: Cl. confidence interval.

Data Collection. Epidemiological data were collected by per-

sonal interview. After informed consent was obtained, a struc-

tured interview lasting approximately 45 mm was conducted bytrained bilingual interviewers. Subjects were asked to describe

the occupation that they had held for the longest period of time.

To assist in assigning the correct occupational codes, detailedinformation was requested on job title, duties on the job, and

equipment used. The participants were also asked to indicate

from a list of defined exposures (either from hobbies or occu-

pations). which they had experienced for at least 8 h/week for

at least I year. Wood dust was one of these specified exposures.At the end of interview. each participant received a $20 grocery

coupon.The occupation each subject had held for the longest

period of time was reviewed blindly by a trained occupational

coder who used a three-digit standard occupational code from

the DOT� of’ 1977, independent of the stated industry (19). Inlike fashion, the industry that had employed each subject the

longest was identified by a two-digit standard industry code inaccordance with the Standard Industrial Classification Manualof 1972, without regard to the stated occupation (20).

Wood-related occupations include forestry and logging

(DOT codes 450-459), processing of wood and wood products

(DOT codes 560-569), wood machining. such as cabinetmak-

ing and pattern making (DOT codes 660-669), and fabrication

and repair of wood products (DOT codes 760-769). Wood-related industries are those that produce lumber; wood prod-ucts. furniture, and fixtures: and paper products (standard in-

dustry codes 24-26, respectively). All occupations andindustries involving wood dust exposure were reviewed and

defined by a certified industrial hygienist. Information was

missing for 7 cases and 6 controls on self-reported exposure andfor 6 cases and 5 controls on occupation.

A smoker was defined as someone who had smoked atleast 100 cigarettes in his or her lifetime. A former smoker was

defined as one who had smoked cigarettes in the past but hadstopped smoking at least 1 year before diagnosis (or 1 year

before the study began. for the controls). Lighter and heaviersmokers were categorized by the 75th percentile pack-year

value for the controls, i.e. , <30 pack-years and �30 pack-

years. which was also the approximate 25th percentile pack-

year for the cases. Pack-year information was missing for2 cases and I 3 controls.

Mutagen Sensitivity Assay. This assay has been described indetail previously ( 14). At completion of the interview, 30 ml ofblood was drawn into hepaninized tubes for the assay. Peniph-

eral lymphocyte cultures were grown in RPMI 1640 mediumsupplemented with 20% fetal bovine serum. On the third day of

incubation, standard lymphocyte cultures were treated with

bleomycin (0.03 units/ml) for 5 h. During the last h. the cellswere treated with Colcemid (0.04 pg/mI) to arrest the cells in

mitosis before harvesting for conventional air-dried prepara-

tions. All prepared slides were coded and stained with Giemsa

without banding. The number of breaks in 50 metaphases/sample was counted and expressed as the average number ofbreaks/cell. Only frank chromatid breaks or exchanges wererecorded: chromatid gaps or attenuated regions were disre-

garded. The slides were read and coded without knowledge ofthe subjects’ case or control status.

Analytical Methods. The linear trend was estimated by the �

test for trend. The differences in continuous variables wereevaluated by Student’s t test. Partial correlation coefficientswere calculated to evaluate the relationship between variables.To test for significant associations among tobacco smoking,wood dust exposure, and cancer risk, univariate ORs were

calculated as estimates of relative risks. Ninety-five % CIs werecomputed according to the method of Woolf (2 1). When the

numbers were small, the exact method was used. Mutagensensitivity was analyzed as a continuous variable, or dichoto-

mized at the level of 1 break/cell (the value of the 75th per-centile of breaks/cell in controls) or categorized by the quartilesof break/cell in the controls. Age was analyzed as a continuousvariable or categorized by the median value of the studypopulation, i.e., 63 years.

To test the hypothesis of an association between lungcancer and wood dust exposure, separate analyses were per-formed for: (a) self-reported employment in wood and furnitureindustries, independent of the type of occupation or self-re-ported exposure; (b) self-reported occupational exposure, with-

out regard to the industry or self-reported exposure list; and (c)

self-reported exposure to wood dust from the list of defined

exposures without regard to the industry and occupation.Finally, a summary variable was computed incorporating ex-

posure in at least one of the above categories.

Stratified analysis was used to test for the interactionbetween wood dust exposure, mutagen sensitivity, and smokingstatus or pack-year (the 75th percentile of pack-year in controlsand 25th percentile of pack-year in cases was around 30 pack-years). Logistic regression was conducted to estimate risks,which were adjusted for multiple factors, with STATA statis-

tical software (22). A stepwise variable selection procedure was

used to determine the best fitting logistic model.

Results

Host Characteristics. Table 1 describes the demographiccharacteristics, history of tobacco use, and educational level ofthe subjects. There were 180 cases, of whom I I 3 (78 men and35 women) were African-American and 67 (48 men and 19women) were Mexican-American. The mean age for both Mex-ican-Amenican cases and controls was 64 years; for African-American cases and controls the means were 60 and 59 years.respectively. Educational attainment of the controls was notsignificantly different from that of the cases (mean years of

education of 10.6 and 9.5, respectively). No marked differencewas noted in the distribution of cases and controls by quartilesof average annual income (data not shown).

Predictably, there were significant differences in smokingstatus between cases and controls. Over 90% of the cases had

ever been smokers, with 40.6% of the cases being formersmokers and 50.6% current smokers, compared with 27.8 and

3 1 .5%, respectively, for the controls. The mean age at smokinginitiation was not different for cases and controls ( 18.4 versus

19.6 years; P > 0.05). However, the mean lifetime tobaccoconsumption (pack-years) was significantly higher for the casesthan for the controls (45.4 versus 12.0; P < 0.001).

The mutagen sensitivity data were available only on asubset of the study population, so that complete data wereavailable for 132 cases and 240 controls (Table 2). The meanbreak/cell value was 1 . 1 1 for the cases and 0.78 for the controls(P < 0.001 ). Fifty-four % of the cases had mutagen sensitivity

scores � 1.00 break/cell, compared with 21 .7% of the controls.There was no significant difference in tnean breaks/cell valuesby histology, wood dust exposure, smoking status, or tumor



Cancer Epidemiology, Biomarkers & Prevention 585

Table 1 Distribution of select host characteristics by case-co ntrol status

No. (�/)

‘� valueCases Controls

(ii = 180) (ii = 270)

Sex

Mextcan-Amencan

Male 48 (71(0 96(70.6)

Female 19 (28.4) 40 (29.4) 0.876

African-American

Male 78 (69.5)) 86 (64.2)

Female 35 (31.0) 48 (35.8) 0.422

Total

Male 126 (70.1)) 182 (67.4)

Female 54 (30.0) 88 (32.6) 0.562

Mean age. yr (SD(

Mexican American 64.1 (l0.5( 63.5 (I 1.9) t).730

African American 59.8 ( I I .3) 58.6 ( I 2.2) 0.424

Education. yr (SD( 9.5 (4.0) 10.6 (5.0) 0.108

Smoking status

Never 16 (8.9) llO(40.7(

Former 73 (40.6) 75 (27.8) <0(8)1

Current 91 (50.6) 85(31.5) <0(101

Pack-yr (SD) 45.4 (34.1 ( 2.0(18.0) <0(8)1

stage. After adjustment for age. sex. ethnicity, pack-year. and

wood dust exposure. mutagen sensitivity (� 1 break/cell) was a

significant risk factor for lung cancer. with an OR of4.3 (CI

2.3-7.9). When subjects were categorized into quartiles of

breaks/cell values, there was a dose-response relationship be-tween lung cancer risk and mutagen sensitivity. with <0.50break/cell as the referent category. The adjusted ORs for mdi-

viduals with increasing breaks/cell were 1.3, 2.3, and 5.5,

respectively. The trend test by linear regression analysis was

significant (P < 0.0001). When lung cancer was categorized byhistological type. mutagen sensitivity was significantly associ-

ated with risk for adenocarcinoma (OR = 5.1: CI = 2.2-I 1.9)

and squamous cell carcinoma (OR = 4.7; CI 1.6-13.4) (data

not shown). The ORs for mutagen sensitivity were even higher

in never smokers (OR = 8. 1 ) and former smokers (OR = 4.8)than in current smokers (OR 2.9). The data were alsostratified by age at diagonosis <63 or �63 years (which wasthe median of the age distribution of the cases and controls).The risk estimate for younger patients was 7.8 (CI 2.8-21.5)

compared with 2.7 (CI = 1 .2-6.2) for older patients.

Wood-related Industries, Occupations, Self-reported Expo-sure, and Lung Cancer. A summary variable of wood dustexposure was estimated from one or more of the followingvariables: longest employment in wood and wood-related in-

dustnies; longest employment in wood and wood-related occu-pations; and exposure list. Controls (9.5%) were exposed towood dust compared to 17.3% of the cases according to thesummary variable (Table 3). In the wood dust-exposed subjects,

50% were employed in sawing occupations, 16.7% in fabrica-

tion and repair of furniture occupations. others in logging and

related occupations. cabinet makers, wood machining occupa-tions. and fabrication and repair of wood products occupations.

Multivaniate analysis showed significantly elevated ORs forself-reported wood dust exposure (OR 3.6; CI 1 .4-9. 1 ), as

well as for the summary variable of wood dust exposure (OR =

3.5: CI = I .4-8.6), after adjustment by age, sex, ethnicity,

Table 2 Risk estimates for mutagen sensitivity in lung cancer cases

and controls

Mutagen sensitivityNo.

Cases

(C%)

ControlsOR” (CI)

Break/cell

�l.00

<1.00

71 (53.8)

61(46.2)

52 (21.7)

188(78.3)

4.3 (2.3-7.9)”

Break/cell”

<0.50

0.50-0.69

0.70-0.95

0.96+

12 (9.1)

19 ( l4.4

30 (22.7)

71 (53.8)

58)24.2)

63 (26.3)

60 (25.0)

59 (24.6)

1.0

1 .3 (0.5-3.8)”

2.3 (0.8-6.2)”

5.5 (2.1-14.5)”

Smoking status

Never

�l.00

<1.00

6(54.5)

545.6

17(17.9)

7882.l)

8.1 (1.9-34.3)’

Former

�l.0()

< I .00

36 (61.0)

23 (39.0)

16 (23.9)

5 1 (76. I)

4.8 (2.2-10.5)’

Cun’ent

�l.00

<1(8)

29 (46.8)

33(53.2)

19 (24.4)

59(75.6)

2.9 ) 1.3-6.5)’

Age at diagnosis

<63 yrs

>IAX)

<1.00

3549.3)

36(50.7)

1906.0)

1(10 (84.0)

7.8)2.8-21.5)”

63+ yrs

� I (8)

< 1.18)

36 (59.0)

25 (41.0)

33 (27.3)

88 (72.7)

2.7 ( I .2-6.2)”

,, Adjusted by age (entered as a continuous variahle. sex. race. pack-year. and

overall wood dust exposure.

,‘ Values corresponding to the quartiles of breaks/cell in the controls.

C Adjusted by age. sex. race. and overall wood dust exposure.

pack-year, and mutagen sensitivity (Table 3). The risk estimatewas elevated but not statistically significant for individuals with

longest employment in wood and wood-related industries andwas similiar to those with longest employment in wood andwood-related occupation. Ethnic-specific analyses showed thatthe adjusted OR was significantly increased for wood dustexposure and lung cancer risk in African-Americans, with an

OR of 5.5 (CI = 1.6-18.9; Table 3). However, no such asso-ciation was noted in the Mexican-Americans. Among the his-

tological subtypes of lung cancer, wood dust exposure was

associated with an increased risk of NSCLC for both African-Americans and Mexican-Americans, but only for African-Americans was the risk estimate statistically significant (Table4) with an OR of 4.8 (Cl = 1.2-18.5). When NSCLC was

further subcategonized by histological type. the ORs for wooddust exposure were significantly elevated for adenocarcinoma,squamous cell carcinoma, and large cell carcinoma for African-

American with ORs of 3. 1 , 3.5, and 10.0, respectively. None ofthe subhistological types was associated with a significantlyincreased risk with wood dust exposure for Mexican-Amen-icans with histological-specific ORs of 3.3. 1 .4, and 0.7.

respectively.

Interactions between Wood Dust Exposure, Mutagen Sen-sitivity, and Smoking. We also performed stratified analysisto assess the possible interactions between wood dust exposure



586 Wood Dust, Mutagen Sensitivity, and Lung Cancer

Table 3 ORs for wood dust exposure

ExposureTotal African-American Mexican-American

Cases Controls OR” (CI) Cases Controls OR” (Cl) Cases Controls OR” (CI)

Expc�ure list

Exposed 28 23 3.6(1.4-9.1) 22 9 4.9(1.4-17.3) 6 14 2.4(0.5-10.6)

Not exposed 145 241 86 120 59 121

Employment in wood and

wood-related

occupations

Exposed 8 4 2.5 (0.4-16.1 ) 7 1 4.3 (0.4-49.8) 1 3 0.2 (0.()-40.5)

Not exposed 66 261 102 128 64 133

Wood dust (overall)

Exposed 3)) 25 3.5 (1.4-8.6) 23 9 5.5 (1.6-18.9) 7 16 2.0(0.5-8.1)

Not exposed 143 239 85 120 58 1 19

I Adjusted by pack-year. mutagen sensitivity ) � I break/cell). age (entered as a continuous variable), sex, and ethnicity.

I, Adjusted by pack-year. mutagen sensitivity ) � I break/cell), age (entered as a continuous variable), and sex.

Table 4 ORs fo r wood dust exposure by histopat hological type

Wood Dust Exposure- OR(C1)Exposed Nonexposed

African-American

NSCLC 16 65 4.8” (1.2-18.5)

Controls 9 I 20

SCLC” 0 9 0.7 (0.0-12.4)

Controls 9 120

Mexican-American

NSCLC 7 27 3.8” (0.8-17.4)

Controls 16 119

SCLC 0 0 0.3 (0.0-6.2)

Controls 16 119

,‘ Adjusted by age (entered as a continuous variable. sex. mutagen sensitivity, and

pack-year. When zero cells appeared. 0.5 was added to each cell and crude ORswere calculated.

,, SCLC. small cell lung carcinoma.

and both mutagen sensitivity and cigarette smoking (Table 5).

The referent group was those not exposed to wood dust andwho were not mutagen sensitive or had never smoked. The ORfor wood dust exposure in the absence of mutagen sensitivitywas 1.9 (Cl = 0.8-4.3); for mutagen sensitivity without wood

dust exposure, the estimate was 3.8 (CI 2.3-6.3). In the

presence of both wood dust exposure and mutagen sensitivity,the OR was 19.7 (CI 4.0-96.8). This combined OR suggeststhat the joint efTect is greater than the multiplicative. However,in the logistic model, the interaction term was not statistically

significant, probably due to small sample sizes in the strata,

which also resulted in the width of the confidence limits. In

spite of the small numbers, the lower limit of the 95% CI was

still 4.0 suggesting that there is a notable association. A similar

effect was suggested for wood dust exposure and smoking

status (ever versus never). The respective ORs for wood dust

exposure, ever having smoked, and the two variables combinedwere 0.3, 5.9, and 43.9, respectively. The effect between wood

dust exposure and pack-years of smoking followed the same

pattern. When ethnic-specific analysis was performed, similarinteraction patterns were observed for African-Americans andMexican-Americans. When the analysis was restricted to just

Table 5 Interaction of wood dust exposure. mutagen sensitivity. and smoking

status

Variable I Variable 2 Cases Controls OR (CI)”

Wood dust exposure Mutagen sensitivity

No No 49 164 1.0

Yes No I I 22 1.9 (0.8-4,3)

No Yes 55 48 3.8 (2.3-6.3)

Yes Yes 12 2 19.7 (4.0-96.8)

Wood dust exposure Smoking status”

No No 16 97 1.0

Yes No 0 9 0.3 (0.0-5.6)

No Yes 127 142 5.9 (3.2-10.9)

Yes Yes 30 16 43.9 (9.5-203.2)

Wood dust exposure Pack-yr

No No 16 97 1.0

Yes No 0 9 0.3 (0.0-5.6)

No Yes 36 95 2.8 (1.4-5.6)

Yes Yes I I 13 21.4 (4.2-108.6)

Wood dust exposure Pack-yr”

No No 16 97 1.0

Yes . No 0 9 0.3 (0.0-5.6)

No Yes ‘A) 35 6.5 (3.9-10.9)

Yes Yes � 19 18.1 (6.2-53.4)

“ Adjusted by age (entered as a continuous variable), sex, and ethnicity. Whenzero cells appeared. 0.5 was added to each cell and crude ORs were calculated.

,, Nonsmokers rersus ever smokers.

‘ Nonsmokers versus <30 pack-year smokers.

,, Nonsmokers t’ersus �30 pack-year smokers.

NSCLC, similar interaction patterns were evident. Size consid-erations prevented us from performing the three-way interac-tions of wood dust exposure, smoking, and mutagen sensitivity.

Discussion

In a recent review of the carcinogenic effects of wood dust,Nylander and Dement (17) highlighted inadequacies in study-

ing the mutagenicity and carcinogenicity of wood dust in lab-

oratory animals and in vitro. Few extractable components ofwood have been thoroughly tested for their cytotoxic and mu-

tagenic effects. Wood dust is a complicated exposure that,

particularly in recent decades, may involve a multitude ofchemical exposures. Carcinogens in wood dust have been



Cancer Epidemiology, Biomarkers & Prevention 587

comprehensively reviewed by IARC and include acrylonitrile,

acrylic fibers, arsenic and arsenical compounds, benzene, buta-diene-styrene copolymers, carbon tetrachloride, coal-tar deriv-

atives, fluorochrome arsenate phenol, and formaldehyde (10).The association of lung cancer and exposure to wood dust

is controversial. Excess lung cancers among workers exposed

to wood have been reported in case-control studies in Louisiana(23), Montreal (24), Shanghai (25), Sweden (26), New Zealand

(27). Georgia (28). Florida (29), and Missouri (15) and incohort studies ( 1 8). In a large case-control study of 4,43 1 cases

and I 1 ,326 controls, Zahm et al. ( 15) showed that lung cancerrisk (especially risk for adenocarcinoma of the lung) was ele-vated for men employed as carpenters and cabinet and furnituremakers. In contrast, several other studies failed to implicatewood dust exposure in lung cancer risk (12, 13). In a nestedcase-control study of male wood workers, Kauppinen et al. (30)also reported no excess of lung cancer among workers exposed

to wood dust.Our results suggest that exposure to wood dust is a risk

factor for lung cancer in susceptible African-Americans but notin Mexican-Americans. However, larger sample sizes areneeded for testing the difference between these two groups.Swanson et al. (3 1 ) observed that the association betweenoccupation and lung cancer was different among African-American and white men. They suggested that Afnican-Amer-icans have historically been given “dirtier” jobs with greater

carcinogenic exposures and highlighted the need to evaluateoccupational exposure by ethnic groups and also to consider

differences in inherent or acquired host susceptibility.In our stratified analysis, the effects of wood dust exposure

and smoking were greater than multiplicative, suggesting thatthere was an interaction between wood dust exposure and

smoking. Our data also support the findings of Stellman andGarfinkel ( 18) who similarly suggested an interaction betweenwood dust exposure and cigarette smoking. This finding is

consistent with the relationship of tobacco smoking to other

lung carcinogens such as asbestos, arsenic, and radon and toother sources of ionizing radiation (32). A similar associationbetween smoking and wood dust exposure and nasal cancer hasbeen observed (33). There are several potential mechanisms forinteraction of wood dust exposure and cigarette smoking. Wood

dust might serve as a cocarcinogen in the initiating stage oftumor development, i.e. , a coinitiating effect. A number ofchentical agents have been shown capable of acting as co-initiators (34-35), i.e., chemicals devoid of tumor-initiating

activity at a particular dose or exposure level but capable ofenhancing the initiating activity of another tumor initiator.

Another potential mechanism for the interaction of wood dustexposure and cigarette smoking is cocarcinogenesis in the formof tumor promotion characterized by chronic inflammation. Ithas been documented that wood dust exposure could causechronic airflow obstruction and chronic bronchitis (36).

There are several inherent limitations in this study. The

study was designed to evaluate genetic susceptibility markersfor lung cancer and, thus, representativeness of the control

group was less of a concern than if the study hypotheses were

based solely on exposure covariates. The use of a conveniencesample for controls raises concerns of bias in assessment and

analyses of potential occupational exposures. It is possible thatthe prevalence of employment in wood-related occupations

could vary with residence and socioeconomic status. Fortu-nately, cases and controls were all drawn from metropolitanSan Antonio or Houston, and there were no significant case-

control differences in educational attainment or family income.The study is also limited by small numbers of subjects in

some strata and by the absence of lifetime occupational data

and documentation of levels, type, and duration of exposures.Recall bias is a potential problem because the study relies onself-reported subjective exposure information. Subjects mayhave been exposed to mixed hard- and soft-wood dusts, and

even those with the same job title may have had extremelydifferent exposure milieus. Finally, we did not have any infor-mation about the processes used.

This study is strengthened by the incorporation of a bio-logical marker of susceptibility to carcinogenesis. We haveshown previously that there is an interaction between mutagensensitivity and cigarette smoking in cancer risk (4), althoughsmoking status, years of exposure, and tumor stage do notindependently modify the sensitivity profile of cases and con-

trols (3). We also demonstrate a suggested interaction (whichappears to be multiplicative) for wood dust exposure and mu-tagen sensitivity. These finding support the hypothesis that

susceptibility to carcinogenesis is an important determinant of

lung cancer risk and that lung cancer occurs in exposed mdi-

viduals with a susceptible phenotype.

Acknowledgments

The authors would like to thank Dr. Lawrence Whitehead for his assistance with

the occupational exposures. Dr. Maureen Goode for editorial assistance. Margo

Graves and Shirley Arbeleaz for interviewing the subjects and obtaining blood

samples. and Shirley Norris for preparation of the manuscript.

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1995;4:583-588. Cancer Epidemiol Biomarkers Prev X Wu, G L Delclos, J F Annegers, et al. sensitivity, and lung cancer risk.A case-control study of wood dust exposure, mutagen

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