epidemiology of coffee and pancreatic cancer1 - cancer … · this paper reports on the results of...

[CANCER RESEARCH 43, 3900-3906. August 1983]

Epidemiology of Coffee and Pancreatic Cancer1

E. L. Wynder,2 N. E. L. Hall, and M. Polansky

Division ol Epidemiology, Mahoney Institute for Health Maintenance, American Health Foundation, New York, New York 10017

ABSTRACT

The association between pancreatic cancer and putative riskfactors was examined using 275 incident cases and 7994 controls interviewed in six United States cities for a major study oftobacco-related diseases. From the comparison population were

excluded patients with other diseases postulated to be associated with pancreatic cancer (e.g., other pancreatic diseases anddiseases of the gallbladder) and those admitted for disordersknown to be associated with smoking.

After carefully controlling for age, the data failed to indicate anassociation between coffee consumption and pancreatic cancer(odds ratio =1.0). This was true both before and after adjustmentfor cigarette smoking and in both males and females. There wasa statistically significant association between pancreatic cancerand smoking in both males and females (odds ratio 3.0 for maleswho smoked more than 1.5 packs/day and 2.0 for females whosmoked more than 1 pack/day).

INTRODUCTION

The etiology of cancer of the pancreas has been the subjectof a number of investigations (3, 11, 14, 18, 19, 32, 33). Whilethe evidence is quite consistent in showing a moderate increasein risk for cigarette smoking, the identity of other etiologicalagents which contribute to worldwide differences in incidencerates of pancreatic cancer remains in question. The associationof dietary fat, both animal and vegetable, with pancreatic cancerhas received support based on both epidemiological and laboratory studies (1, 4, 13, 15, 32). One postulated mechanism ofdietary fat action is by the control of the amount and nature ofthe pancreatic secretions, which may in themselves act as enhancing or promoting stimuli. Another factor reported to beassociated with increased pancreatic cancer risk is occupationalexposure, such as to oil refining, paper manufacturing, and avariety of other industries as well as occupations not associatedwith exposure (e.g., managers and administrators) (22, 24).Diabetes, pancreatitis, and heavy alcohol consumption have alsobeen reported, although inconsistently, to be associated withpancreatic cancer (16, 31, 33).

Recent studies have produced equivocal and controversialevidence of the possible relationship between coffee consumption and risk of pancreatic cancer. While there have been anumber of reports that demonstrate an association betweenpancreatic cancer and coffee consumption (8, 18, 20, 23, 28),there have also been a number of reports that demonstrate noassociation (2, 9, 12, 26, 27). At this time, there is no evidencefrom bioassays documenting a carcinogenic potential for coffeeextract. Coffee is known to contain caffeine, in addition to several

' Supported in part by USPHS Contract N01-CP-05684, Grant CA32617 from

the National Cancer Institute, and American Cancer Society Special InstitutionalGrant SIG-8.

2To whom requests for reprints should be addressed.

Received October 26. 1982; accepted April 21. 1983.

suspected and known animal carcinogens (e.g., polyaromatichydrocarbons) and cocarcinogens including the catechols, postulated to affect A/-nitrosamine production (1, 7, 17). Although

certain inferences can be made to support a role in humancarcinogenesis, many of the mutagenic components present incoffee are also present in other common foods including roastedmeats. Further detailed study of the possible relationship ofcoffee consumption in the etiology of cancer of the pancreas ishighly pertinent, both as a public health issue and in view of theconsiderable public attention given the current conflicting data.This paper reports on the results of a case-control study of the

association of pancreatic cancer and smoking, alcohol consumption, and coffee drinking habits.

MATERIALS AND METHODS

The American Health Foundation has been interviewing tobacco-

related cancer cases and controls in hospitals since 1969 (35). The studysubjects were cases with tobacco-related diseases and matched hospitalcontrols with non-tobacco-related diseases. Interviewers reviewed the

daily admission records in each participating hospital. For the presentstudy, charts of patients with admitting diagnoses of pancreatic cancer,possible pancreatic cancer, and pancreatic tumor or mass were checkedto determine eligibility. All pancreatic cancer patients were consideredeligible if they had been diagnosed with histologically confirmed primarypancreatic cancer and were between the ages of 20 and 80. Within 2months of the case interview, controls matched on the basis of age (Â±5years), race, sex, and room status (ward versus nonward) were interviewed by trained interviewers in the same hospital. Interviews tookplace within 6 months of the time of diagnosis in 17 hospitals in 6 majormetropolitan areas in the United States (New York, Birmingham, Pittsburgh, Philadelphia, Chicago, and San Francisco). The hospitals includedfederal Veterans Administration, public, private, and tertiary cancer careinstitutions.

In 1981, of 160 patients screened, there were 73 completed interviews(45%). Twenty-three % were not interviewed because of physician or

personal refusal, illness, psychiatric complications, inability to speakEnglish, or discharge or death prior to interview. Twenty % were notinterviewed because the diagnosis was not confirmed, and an additional12% were ineligible because they were diagnosed more than 6 monthsprior to interview. Thirty-five % of controls completed interviews. The

refusal rate (25%) was similar to that of the cases. However, over 40%were ineligible for interview because they were diagnosed more than 6months earlier.

The interview contained questions on a number of variables includingdemographic characteristics. When questions concerning personal habitswere asked, the interviewer directed the patient to answer on the basisof habits in the year before diagnosis. A number of questions, includingbrand used, were asked about tobacco use. Coffee consumption habitswere elicited by questioning the usual number of cups daily. This studyreports the results from 275 incident cases of cancer of the pancreas(153 males and 122 females) and 7994 controls interviewed during theperiod between 1977 and 1981. Because of the small number of cases,our comparison sample was not restricted to those matched to the cases(1:1). To maximize the power of the study, we did not carry out amatched analysis. We did a stratified analysis which used the large pool

3900 CANCER RESEARCH VOL. 43

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Pancreatic Cancer, Smoking, and Coffee

of 7994 controls interviewed as matches for other cases in the sameperiod and in the data base of our ongoing study.

Due to the design of the larger study, the disease diagnoses of thecontrols included a spectrum of clinical conditions not associated withtobacco use (all cancers, 36% male and 47% female; including gastrointestinal tract, 8 and 7%; prostate, 9 and 0%; breast, 0 and 12%; otherfemale genital, 0 and 6%; skin, 5 and 5%; other nontobacco cancersincluding leukemia, lymphoma, thyroid, and sarcoma, 14 and 17%;noncancers including infectious diseases, 4 and 3%; trauma, 8 and 5%;hernias and disc, 4 and 2%; arthritis, 1 and 2%; benign prostatichyperplasia, 4 and 0%; benign neoplasms, 9 and 12%; and othernonneoplastic diseases, 12 and 18%). Controls were excluded based onan admitting diagnosis of the following tobacco-related diseases: cancers

of the respiratory tract, esophagus, oral cavity, pancreas, liver, kidney,and bladder, and myocardial infarction; also excluded were cirrhosis,chronic bronchitis and emphysema, stroke, and gastric ulcer. Given thehigh frequency of misdiagnosis of pancreas cancer, this study benefitsfrom all cases having histologically confirmed diagnoses. Additionally, toreduce possible bias, we excluded controls with diagnosis of conditionspostulated to be associated with pancreatic cancer (nonneoplastic pancreatic diseases, gallbladder disease and gallbladder cancer, and diabetes).

Analysis. To study the association of factors with pancreatic cancerrisk, the control population was adjusted by the direct method (5) to thatof the cases for age (5-year groupings) and, when stated, other factors

including smoking, religion, and hospital. Subjects were classified asexsmokers if they had stopped smoking at least 1 year prior to diagnosis.For adjusment purposes, smoking was divided into several categorieswhich included never smokers (only those individuals who never smokedany tobacco product), 4 levels of current cigarette smokers, (1 to 10,11to 20,21 to 30, and 31 + cigarettes/day), 3 levels of ex-cigarette smokers(<15 ex-years at 1 to 20 cigarettes/day; <15 ex-years at 21 + cigarettes/day; >15 ex-years, all ex-cigarette/day categories), and a category

composed of pipe and cigar smokers. Pipe and cigar smokers includedonly those people who were never cigarette smokers. Other factorswere adjusted for, with the distributions shown in Table 2.

Unadjusted and adjusted relative risks (odds ratios) were computedto study the associations between putative risk factors and pancreaticcancer. Relative risks were calculated as exposure odds ratios with 95%confidence intervals calculated using the method of Woolf (25). Therelative risks and 95% confidence intervals were computed individuallyfor the risk factors thought to be associated with the occurrence ofpancreatic cancer. Statistical tests for significance used included x2 tests

for independence (10).

RESULTS

Coffee as a Possible Confounder

Prior to our final analysis, we investigated coffee use in thereferent population to measure the presence and extent of itsinteraction with other known and postulated risk factors. Consumption of coffee Â¡sa common habit. In our population ofpatients hospitalized for diseases that are not related to tobaccousage (including cancer), 83% of the males and 80% of thefemales regularly drank coffee (Charts 1 and 2).

The age- and sex-specific coffee drinking habits of this control

population were similar to those reported in the National HealthSurvey (6) (Chart 3). The data indicated an age-dependent pat

tern for coffee consumption. In addition to an overall decreasein amount consumed, in our sample, older people were morelikely to drink decaffeinated coffee (Table 1).

As expected, when coffee drinking was examined in relationto smoking habits, not only did more heavy smokers drink coffee,

IOO .

'39 40

Chart 1. Distribution of males by daily coffee consumption and age: AmericanHealth Foundation population, 1977 to 1981.

IOO

50

'39 40

Chart 2. Distribution of females by daily coffee consumption and age: AmericanHealth Foundation population, 1977 to 1981.

IOO .

80

Chart 3. Distribution (%) of people by daily coffee consumption and age: UnitedStates, 1976(6).

but heavy smokers who drink coffee were also heavy coffeedrinkers (Charts 4 and 5). The percentage of those drinking 6cups of coffee or more was more than twice as great amongheavy cigarette smokers as compared to nonsmokers. No consistent associations were found when coffee drinking habits wereexamined in relation to other variables (i.e., occupation status,education, religion, and alcohol usage).

Epidemiology of Pancreatic Cancer

The demographic breakdown of the case and control population for the variables investigated is shown in Table 2. The studyanalysis examined the association of coffee and other variableswith pancreas cancer.

Smoking. To measure the association of pancreatic cancerand smoking, pancreatic cancer cases were compared to controls, standardizing for age (Table 3). Smoking was a statisticallysignificant risk factor. In males, the risk associated with smokingincreased with number of cigarettes smoked 3-fold for thosesmoking over 1.5 packs/day in comparison to those who did not

AUGUST 1983 3901



E. L. Wynder et al.

Table 1Age-specific coffee drinking habits by type

Non-coffeedrinkersAge(yr)Male

controls<3940-4950-5960-6970+TotalFemale

controls<3940-4950-5960-6970+TotalNo.72137339304100952438717315062515%282018151817.4252221182120.4Regular

onlyNo.1674481236123931934111122434804341441413%656464625662.4646157534855.9DecaffeinatedonlyNo.10591542299054212259311951300%48816169.97611151711.9Regular

anddecaffeinatedNo.952203239615648459011440297%3710121110.351111141311.8TotalNo.2586961934201157054691754008368172972525%4.712.735.436.810.41006.915.833.132.411.8100

MALES N- 5469

3-5

U

&

.100FEMALES N - 2525

I-o

SMOKING CATEGORY

Chart 4. Coffee drinking for each smoking category (males).

use any tobacco product (95% CI3 = 1.67 to 5.53). The 2-fold

elevation in risk associated with pipe and cigar smoking wasalso statistically significant (95% CI = 1.07 to 3.66). Becausecertain demographic factors could be related to pipe and cigarsmoking, further analyses standardized for hospital (Memorialversus other) and religion (Jewish versus other), in addition toage, were performed. The results were independent of thesefactors. In females, there was also a statistically significantincrease in relative risk associated with cigarette smoking (oddsratios of 2.0 for those smoking more than 1 pack/day; 95% CI= 1.05 to 3.80). These findings are similar to and consistent withprevious reports which demonstrate an association betweencigarette smoking and pancreatic cancer (3,10,14). We obtainedalmost identical results when the analysis was done with cancercontrols and noncancerous controls separately.

Coffee. To assess the association between coffee and pan-

3-5

HIUlili,oo

o

-IOO

- 50s

l

3The abbreviation used is: CI, confidence interval.

SMOKING CATEGORY

Chart 5. Coffee drinking for each smoking category (females).

creatic cancer, the data were first examined after adjustment forage, and then examined after adjustment for both age andsmoking. In both cases, the odds ratio deviated little from unity.There was no association between coffee drinking and pancreatic cancer (Table 4). The data indicated no relationshipbetween coffee consumption per se or by quantity of intake withpancreatic cancer for either men or women. This was true bothbefore and after standardization for cigarette smoking. Becauseof the possible confounding effect of illness on coffee drinkinghabits, we also analyzed the data with cancer and noncancercontrols separately. For both males and females, following ageadjustment or age and smoking adjustment, using either groupof controls, there was no association between coffee drinkingand pancreatic cancer. No dose-response was seen, with a range

of odds ratio estimates from 0.7 to 1.4. Since the different controlgroups did not materially change any of the odds ratio estimates,the results using the total control series were chosen for presentation.





Table 2

Demographic description of cases and controls by percentage

MalesCasesTotalAge

(yr)s3940-4950-5960-6970+ReligionProtestantCatholicJewishOtherEducation

(yr)1-111213-1516+OccupationProfessional/managerialSales/clericalBlue

collarHousewifeCoffee

consumption0cups/day1cup/day2

cups/day3-cups/day>5

cups/dayCityNew

YorkBirminghamPittsburghPhiladelphiaChicagoSan

FranciscoAlcohol

use0oz/day<1

oz/day1-2.9oz/day3-4.9oz/day5+

oz/daySmokingNonsmokerPipe-cigarExsmokerPresent1-20

cigarettes/day21-30cigarettes/day31+

cigarettes/dayNo.1535135358246346321054402631531880241534502891419151014224529134127185226820%3.38.534.637.915.741.730.521.56.635.826.517.220.535.111.953.015.99.922.533.118.559.52.612.49.86.59.214.730.019.38.727.317.911.934.417.25.313.2ControlsNo.54692586961934201157023701692934467190014138021353199060428829527391064187084420241004758641718324101317431149552101016445221609970260414%4.712.735.436.810.443.330.917.18.534.725.814.724.836.411.052.617.413.519.534.215.437.018.413.911.713.15.918.531.921.010.118.430.39.629.617.94.87.6FemalesCasesNo.12241535462237483073947221416332548251925361766318132242441612756262766%3.312.328.737.718.030.339.324.65.732.038.518.011.413.127.020.539.320.515.620.529.513.954.12.514.810.718.034.736.413.29.95.846.321.422.35.05.0ControlsNo.252517540083681729794993945917677289342243848968646388751538855375431511153311234222812539781033335997914414384528690%6.915.833.132.411.837.637.218.27.030.635.416.817.319.427.215.935.120.415.421.929.912.544.213.14.916.711.110.038.740.913.33.93.157.417.518.03.43.6

Other Possible Factors. When the effect of alcohol wasexamined, no significant association between alcohol consumption and pancreatic cancer was apparent (Table 5).

Following standardization for the 2 risk factors known to beassociated with pancreatic cancer, age and smoking, we lookedat the effect of other demographic factors on the risk of pancreatic cancer. When the variables defined in Table 2 were testedby x2 tests for independence, no statistical association was

found for education, religion, or occupational status with pancreatic cancer.

DISCUSSION

The results confirmed previous reports of an association between cigarette smoking and pancreatic cancer (33). Any consideration of causation needs to be viewed in light of internal andexternal consistency of the data. The association between smoking and pancreatic cancer satisfies these criteria. The resultsshowed a consistent dose-response and temporal relationshipand a plausible biological mechanism.

In contrast to recent findings by MacMahon ef al. (20), the

AUGUST 1983 3903



E. L. Wynder et al.

Tab)e3Age-standardized odds ratios tor pancreatic cancer by smoking characteristics

MalesSmoking

status8NonsmokerCurrent1-10

cigarettes/day11-20 cigarettes/day21-30 cigarettes/day31+cigarettes/dayExsmokerPipe/cigarTotalCases17.62.6

14.45.9

13.134.611.8153All

controls(%)29.04.811.1

4.27.133.99.85464Odds

ratio1.00.9

2.12.33.01.72.0CI0.31-2.58

1.13-4.061.06-5.011.67-5.531.04-2.721.07-3.66Cases46.39.113.2

10.1621.5121FemalesAll

controls(%)57.3CO

COCMCO0CO19.22525Odds

ratio1.01.8

1.52.01.4CI0.92-3.49

0.85-2.671.05-3.800.86-2.24

a When only cigarette smokers and never smokers are investigated for trend, the XZM- EXT= 17.39 for mates (<0.001)

and 6.00 for females (p < 0.025) (21).21+ cigarettes/day.

Table 4Odds ratios for pancreatic cancer by coffee drinking characteristics

Males Females

Total cups coffee/dayCases All con- Odds

(%) trois (%) ratioCases All con- Odds

(%) trois (%) ratio

No. of cases studied 153 5469 122 2525

Age- and smoking-adjusted

CI

0123-56+15.99.922.533.118.5Age-adjusted 17.01.014.120.134.214.60.81.21.01.40.39-1.440.71-2.040.63-1.690.78-2.3520.515.620.529.513.920.216.022.329.811.81.01.00.91.01.20.52-1.770.52-1.600.58-1.650.84-1.60

0123-56+No.

of cases studies15.99.922.533.118.515315.812.819.534.017.954691.00.81.11.01.00.40-1.480.68-1.950.59-1.590.59-1.7920.515.620.529.513.912218.916.121.130.613.225251.00.90.90.91.00.48-1.640.51-1.590.53-1

.500.52-1.83

TablesAge- and smoking-ad/ustedodds ratios for pancreatic cancer by alcohol consumption

Mates Females

Alcohol use Cases Controls Odds(oz/day) (%) (%) ratio CI

Cases Controls Odds(%) (%) ratio CI

0<11-33-55+Total14.730.019.38.727.315317.630.620.610.320.954691.01.21.11.01.60.70-1.960.64-1.960.51-2.010.92-2.6338.740.913.33.93.112236.441.913.84.43.425251.00.90.90.80.90.61-1.380.51-1.610.32-2.180.29-2.05

present study found no association between total coffee consumption and cancer of the pancreas. Assuming an increase inrisk of 2.0, power calculations showed that, with males andfemales analyzed separately, our study power was 0.74 and0.68, respectively (25). On the other hand, while showing no riskassociated with coffee drinking, the present study did indicate adose response for cigarette smoking of a magnitude similar tothat demonstrated in other retrospective and prospective studies(3,14,32,33).

The study showed that there is a high correlation betweencigarette smoking and coffee consumption. Therefore, demonstration of an independent association for coffee requires carefulstatistical control for smoking, a known risk factor. Appropriatestandardization requires use of a large number of smokingcategories that reflect the increase in pancreatic cancer riskassociated with increase in cigarette consumption.

In view of the probable causative association of smoking andpancreatic cancer, the lack of any significant association between





these factors in males in the MacMahon Study (20) suggests aninherent problem. Differences in definitions or classifications usedin their smoking categories may be responsible for the disparatefindings. Prior investigators have shown that the risk associatedwith light or moderate cigarette smoking is nominal. The inclusionof 20 cigarettes/day in the heavy cigarette smoking categorymay have resulted in weighting the heavy smoking categorytoward the 1 pack/day direction and, concomitantly, may haveminimalized an apparent association of heavy smoking withpancreatic cancer. Another difference between this and MacMahon's analysis was in the treatment of the pipe and cigarsmokers. In MacMahon's analysis of smoking risk, only cigarette

smoking habits were considered. This is important, since thecategory of pipe and cigar smokers, a weak statistically significant risk factor in this study, contains about 10% of our malestudy subjects (both cases and controls), and has been mentioned as a risk factor in other studies (3, 33).

Hospitalized controls, many with cancer, may in fact be anonrepresentative comparison population for an analysis of pancreatic cancer risk. However, since the coffee drinking habits ofour controls were comparable to the general nonhospitalizedpopulation interviewed in the National Health Survey, we believethat the control population was adequate for comparison. Inaddition, analyzing the cancer controls and noncancer controlsseparately yielded the same results.

A potential pitfall in this study, and in any interview study, isbiased or random misclassification of responses. Over 90% ofthe interviews used in this study were completed before theMacMahon study was reported linking coffee use and pancreaticcancer. Therefore, the resulting publicity, which might be predicted to affect the interviews or the respondents' answers,

would not materially change the data. In addition, while misclassification of the responses might be predicted to affect the doseresponse of a factor, only a change in classification of a "never"or "occasional" coffee drinker to a "1+ cup/day" coffee drinker

or vice versa would affect the question of exposure. Since noonus is associated with coffee drinking and such a question isrelatively straightforward, it is unlikely that random misclassification influenced our results showing no relationship betweencoffee use and pancreatic cancer.

The lack of an association between coffee and pancreaticcancer reported in this study is supported by a number of recentreports of retrospective studies (9, 12, 27). Also, studies on percapita consumption of coffee did not show a strong associationof increased mortality from pancreatic cancer after appropriateadjustment for cigarette smoking (2, 8). Per capita consumptionof coffee in Sweden and Finland is about 5 times higher thanthat in the United Kingdom without a concomitant increase incancer of the pancreas. In addition, although nonwhites in theUnited States have a higher rate of pancreatic cancer than dowhites, their intake of coffee is significantly lower. (Our datashow that 40% of black males compared to 15% of white malesdo not drink coffee.)

Stocks' widely cited 1970 report (28), which showed a strong

association between pancreatic cancer mortality and coffee consumption in males, did not control for cigarette consumption.Stocks reported only a weak association between cigaretteconsumption and lung cancer mortality, and no association between cigarette consumption and other known tobacco-related

cancers. Thus, while some lifestyle characteristics which may be

associated with coffee consumption, such as smoking or dietaryhabits, may be risk factors for pancreatic cancer, the evidencefor the role of coffee in the etiology of the disease is inconsistent.

The present study did not show an association between lowor moderate alcohol drinking and pancreatic cancer. The smallincrease in risk seen in male heavy drinkers was not statisticallysignificant and may be spurious.

The issue of decaffeinated coffee could not be adequatelyaddressed in the present study, since information on duration ofdecaffeinated coffee use was not available. The data on age andcoffee consumption suggested an increase in decaffeinated coffee consumption with advancing age. In addition, coffee use wasinfluenced by the personal health of an individual. Duration datawill obviously be necessary before analysis on decaffeinatedcoffee can be done. As an extension of this investigation, suchduration data are currently being collected. The data presentedhere do not address and therefore do not negate a role fordecaffeinated coffee.

In summary, a case-control study of pancreatic cancer con

firmed a low order association of cigarette smoking to cancer ofthe pancreas. It showed no association between consumptionof coffee and cancer of the pancreas.

The 1964 Surgeon General's Report (29) included an eloquent

discussion on judgment for causation in epidemiology. It is ourcontention that, as epidemiologists increasingly deal with weakassociations, the principles in the Surgeon General's Report are

often overlooked, and the data tend to be stretched beyond theirelasticity.

By analogy, it would seem that the same criteria can be usedto establish a finding of "no association." Although not as

exciting to the investigator and certainly not to the media,establishing that no association exists between 2 variables is ofequal importance to scientific knowledge. If the criteria of judgment for causation in the Surgeon General's Report are used to

assess the data presented in this paper, we can conclude thatthere is, in fact, no association between the consumption ofcoffee and cancer of the pancreas.

ACKNOWLEDGMENTS

We gratefully acknowledge the following cooperating institutions and individuals:Memorial Hospital, Dr. David Schottenfeld; Manhattan Veteran's Hospital, Dr.

Norton Spritz; Long Island-Jewish Hillside Medical Center, Dr. Arthur Sawitsky;University of Alabama Hospital, Dr. William Bridgers; Birmingham Veteran's Hos

pital, Dr. Herman F. Lehman; Loyola University Hospital (Chicago), Dr. Walter S.Wood; HiÃ±esVeteran's Hospital (Chicago), Dr. John Sharp; Hospital of the Univer

sity of Pennsylvania, Dr. Robert M. Levin; Jefferson Medical College and ThomasJefferson University Hospital, Dr. J. A. Colberg; Allegheny General Hospital (Pittsburgh), Dr. Stanley A. Briller; University of Pittsburgh Eye and Ear Hospital, Dr.Lewis H. Kuller; Pittsburgh Veteran's Hospital, Dr. Eugene N. Myers; Moffitt

Hospital (San Francisco), University of California at San Francisco, and CountyHospital (San Francisco), Dr. Nicholas Petrakis; and St. Luke's Hospital (San

Francisco), Dr. Richard A. Bohannan.The authors also wish to thank Dr. L. Breslow, Dr. J. Fraumeni, Dr. N. Hanis,

Dr. I. Higgms. Dr. E. Millner, Dr. J. Schlesselman. Dr. P. Stolley, and Dr. A. Zauberfor reviewing and commenting on previous drafts of the manuscript, and M. Nanfaroand M. Hewson for assistance in manuscript preparation.

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1983;43:3900-3906. Cancer Res E. L. Wynder, N. E. L. Hall and M. Polansky Epidemiology of Coffee and Pancreatic Cancer

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