CIGARETIE SMOKING AND BODY FORM IN PEPTIC ULCER

GASTROENTEROLOGY Copyright @ 1970 by The Williams & Wilkin. Co. Vol. 58, No.3 Printed in U.S.A. CIGARETIE SMOKING AND BODY FORM IN PEPTIC ULCER RICHARD R. MONSON, M.D. Department of Epidemiology, Harvard School of Public Health, Boston, M assachusetis The cigarette smoking histories of physicians with peptic ulcer have been determined. Physicians with gastric or duodenal ulcers have smoked more than comparable control subjects. Those with duodenal ulcer started smoking at an earlier age than did control subjects. However, among those physicians who smoked cigarettes, patients and control subjects did not differ in percentage who had stopped, years smoked, or number of packs smoked per day. It is suggested that cigarette smoking and peptic ulcers result from a common cause; the role of smoking in the etiology of ulcer must be questioned. Body form as measured by height, weight, and ponderal index (height/ ~ weight) was compared between smokers and nonsmokers as well as between patients and control subjects. These comparisons were made for age 21 and for the time of the study in 1968. Physicians with duodenal ulcer were more slender than controls in 1968, but did not differ at age 21. The reported linearity of persons with duodenal ulcer therefore may be secondary to the ulcer rather than associated directly with a cause of ulcer. Physicians with gastric ulcer did not differ from controls. No association between body form and cigarette smoking could be demonstrated among duodenal ulcer patients; control smokers as well as all smokers were significantly more slender than nonsmokers in 1968 but not at age 21. In 1927 Barnett reported the first investigation of smoking and peptic ulcer in which a control group was used. 1 He concluded that "there is no proof that smoking is of any importance in the etiology of. peptic ulcer or gastric neurosis." In his series, 82% of males with peptic ulcer and 75% of male controls matched for age had smoked tobacco. This difference of 7% is not statistically significant at the 1% level, as used by Barnett, but is significant at the 5% level. Trowell reported in 1934 that Received September 12, 1969. Accepted October 13, 1969. Address requests for reprints to: Dr. Richard R. Monson, Department of Epidemiology, Harvard School of Public Health, 665 Huntington Avenue, Boston, Massachusetts 02115. This work was supported in part by Grant 5 T01 GM7 from the National Institute of General Medical Sciences, National Institutes of Health, United States Public Health Service. not only did more patients with duodenal ulcer smoke cigarettes than did control subjects, but also a greater percentage of those with duodenal ulcer inhaled. 2 Among the smokers, however, the average number of cigarettes smoked per day did not differ between cases and controls. Three subsequent clinical studies of the relationship between smoking and ulcer concluded that cessation of cigarette smoking increased the rate of healing of an ulcer but that reduction in the amount smoked was of no value.3-5 Two recent studies6 7 have confirmed the findings of Barnett and Trowell. Doll and his co-workers not only determined the smoking histories of patients with ulcer, but also manipulated the smoking habits of some patients during treatment. Their findings in male ulcer patients were: (a) more patients with gastric ulcer had smoked than either control subjects or 337

338 MONSON Vol. 58, No.3 patients with duodenal ulcer, (b) no relation between amount smoked and the future development of either type of ulcer could be determined, and (c) healing of gastric ulcers was hastened if smoking was stopped during therapy. These authors studied a postulated cause (smoking) in persons with a disease (peptic ulcer). Others have investigated ulcer in smokers and nonsmokers both as to morbidity and mortality. In a group of 1000 men aged 60 to 69, about 50% more ulcers had occurred in smokers than in nonsmokers.s In three prospective studies of mortality, smokers had higher death rates from ulcer than nonsmokers, with the mortality ratios being higher for gastric than for duodenal ulcer.9-11 In summary, it seems that, while cigarette smoking is deleterious in persons who have already developed an ulcer, the role of cigarettes in the etiology of ulcer is questionable because of the lack of a relationship between amount smoked and extent of risk of ulcer. However, even for lung cancer, in which there is a marked correlation between amount smoked and occurrence of disease,9-11 objections have been raised to the conclusion that smoking is of etiological importance.12-13 Fisher was particularly vehement in his protests.12 He felt that smoking and lung cancer could both be results of a common cause, for example, genotype. Comparisons of the emotional status of smokers and nonsmokers have shown that smokers are more neurotic14 or more extraverted.15 While these differences could be due to different genotypes, it is of course possible that they merely reflect differences in smoking habits.14 Another measure of genotype has had a long and varied history in its association with smoking as well as with peptic ulcer. The relation of body build to peptic ulcer has been reviewed by several authors.16. 17 It is agreed generally that persons with ulcer tend to be linear or slender. While many of the older studies failed to define adequate control groups or did not take into account the effect of ulcer on the body build, such linearity is felt to be "manifest in skeletal dimensions" 17; these are of course essentially unchanged in adults after development of an ulcer. In contrast, smokers have been reported to be heavier and taller than nonsmokers as well as larger in various anthropometric dimensions.1s Other authors, however, could find no difference between smokers and nonsmokers with respect to either height or weight.19 Most previous studies have compared the smoking habits of persons hospitalized with ulcers with those of persons hospitalized with other diseases. Although attention has been given to selecting controls who have diseases not known to be associated with smoking,6 it is desirable to study smoking and ulcer in a nonhospitalized population. The ulcer experience of almost 9000 physicians recently has been determined.20 Comparison was then made of the smoking histories and body forms of those with ulcer and of a sample of those without ulcer. Methods The method and results of a survey of peptic ulcer in Massachusetts physicians have been discussed previously."" Upon completion of the survey, to which over 90% responded, the physician population was divided into three categories: males who attended medical school in the United States or Canada, males who trained elsewhere, and all females. The separation for males was made because those who did not attend a United States or Canadian medical school constituted a heterogeneous population. Too few females reported ulcers to permit a similar separation. AI: 1 comparison sample matched for year of birth was selected at random from each of the three categories of physicians without ulcer. In April 1968, 6 months after the initial questionnaire, a second questionnaire was sent to those with the history of an ulcer (patients) and to those without (control subjects). In three mailings of the questionnaire 78.9% (645 of 818) of the patients and 75.9% (621 of 818) of the control subjects responded. Smoking history was not reported for 2 of the patients and 6 of the control subjects. There was no indication that nonrespondents differed from respondents to any significant degree. Where applicable, physicians were asked to give the

March 1970 SMOKING AND BODY FORM IN ULCERS 339 years that they started and stopped smoking and the type of tobacco product used at ages 20, 30, 45, and 60. Persons who were cigarette smokers also were asked to indicate the number of packs per day that had been smoked at these ages. A cigarette smoker was defined as one who had smoked at least 1 cigarette per day for at least 1 year. Ten per cent of the patients and 14% of the control subjects gave a history of pipe or cigar smoking alone; these physicians were defined as nonsmokers. Inasmuch as control subjects were matched to ulcer patients by year of birth, the age at diagnosis of the patient was used as a reference age for the control. In the subsequent discussion of cigarette smoking habits, the term "age at diagnosis" is used for both patients and control subjects. Physicians also were asked to give their current height and weight and their weight at age 21. The ponderal index (height/ ~ w e i g h t ) was calculated for each of these ages. Since the cube root of weight is in the denominator of this measure of obesity, an increase in weight at a constant height results in a decrease in the ponderal index. It was assumed that height remained constant after age 21. Information on body measurements at age 21 was obtained since this is prior to the age when diagnosis of most ulcers was made. Thus, there could not be an effect of the ulcer on the body form. Male patients trained in the United States were subdivided after the initial survey into three groups: (a) those with definite gastric ulcers, (b) those with definite duodenal ulcers, and (c) those with ulcers diagnosed on the basis of clinical symptoms only. The smoking habits and body measurements of the groups of patients were compared with the entire group of control subjects. Since patients with gastric ulcer were older and clinically diagnosed patients were younger than the control subjects, the Mantel-Haenszel summary X' test was used to test for significance of differences in smoking habits. For other comparisons, simple X' tests were used. The Student's t-test was used in comparing average ages. Results Smoking and peptic ulcer. The cigarette smoking habits of patients and control subjects of the three categories of physicians are presented in table 1. In this table only, those physicians who started smoking after the age at diagnosis are defined as nonsmokers. These were primarily physicians whose age at diagnosis was prior to 21. Except for the clinically diagnosed patients, a history of smoking was more common in all categories of physicians with ulcer than in comparable control subjects. Within the category of males who trained in the United States or Canada, past smoking habits are analyzed in table 2. At each of four ages, 20, 30, 45, and 60 years, physicians who had lived to at least that age are compared as to the percentage TABLE 1. Percentages of ulcer patients and control subjects who had smoked cigarettes prior to the age at diagnosisa Category Group Total no. No. Cigarette smokers Percentage P valueb Males trained in the United States Duodenal cases 452 307 67.9 or Canada Gastric cases 52 42 76.2' Clinical cases 46 22 53.5' Controls 530 295 55.7 Other males All cases 62 42 67.7 Controls 51 25 49.0 All females All cases 31 15 48.4 Controls 34 8 23.5 <0.001 <0.001 "'0.3 <0.05 <0.05 a See text for definition of age at diagnosis. b Each group of cases was tested against the corresponding group of controls, Age adj usted to the age distribution of the controls.

340 MONSON Vol. 58, No.3 TABLE 2. Past cigarette smoking patterns of ulcer patients and control subjects at four ages Age Duodenal ulcer patients Percentage smoking cigarettesa Gastric ulcer patientsb Percentage of smokers who were smoking more than one pack per day Duodenal Gastric Control subjects ulcer ulcer Control patients patientsb subjects --- --- 20 52.7t (452) 40.1 (52 ) 38.9 (530 ) 27.3 38.8 30.1 30 65.0t (448) 76.9t (51 ) 53.7 (518 ) 43.0 45.7 47.1 45 52.5* (366 ) 72.7t (44) 42.9 (413 ) 49.5 60.2 46.9 60 35.4 (161 ) 32.6 (26 ) 27.2 (184 ) 40.4 54.1 44.0 Average age smoking started 19.5* 21.2 20.3 A verage age in 1968 54.2 56.7 53.6 a N umbers in parentheses are total number of physicians living at each age. Statistically significant differences between duodenal or gastric ulcer patients and control subjects: *, P < 0.05; t, P < 0.00l. b Age adjusted to the age distribution of the controls. who were smoking at that age. Also, among those who still were smoking, the percentage who smoked more than one pack per day is indicated. At all ages, about 1.3 times as many duodenal ulcer patients as control subjects were smoking. Also, duodenal ulcer patients started smoking significantly earlier than control subjects. However, among smokers, there was no difference between duodenal ulcer patients and control subjects as to amount smoked at each age. Gastric ulcer patients differed from control subjects to essentially the same degree, except that the average age when they started smoking was no different from that of the controls. It should be pointed out that comparison of patients and control subjects at several ages in the past does not result in independent probabilities of significant differences. The differences noted in table 2 are essentially reflections of the differences in table 1. The percentages of duodenal ulcer patients and control subjects who were smoking at the above four ages with respect to the age at diagnosis are compared in table 3. The smoking habits prior to diagnosis are noted above the dashed line; for example, for physicians whose age at diagnosis was between 30 and 44 years, smoking habits prior to diagnosis are at age 20 and 30. For all ages at diagnosis, duodenal ulcer patients had smoked to essenti ally the same relative excess at all ages prior to diagnosis. In other words, the percentage of duodenal ulcer patients who smoked at age 20 shows no relative increase between that age and the age at diagnosis. Except for those whose age at diagnosis was 60 years or above, duodenal ulcer patients started smoking at an earlier age than did control subjects. Duodenal ulcer patients and control subjects were found to be similar in other comparisons. Among those who had ever smoked, 61.3% of duodenal ulcer patients and 61.2% of control subjects have stopped; the average ages at stopping were 43.9 and 44.3 years, respectively. The average length of time that physicians had smoked prior to the age at diagnosis was 18.3 years for duodenal ulcer patients and 18.1 years for control subj ects. Cigarette smoking, body form, and peptic ulcer. Those physicians whose age at diagnosis was less than 21 or whose height or weight was not given are not included in tables 4 and 5. Height, weight, and ponderal index at age 21 and at the time of the study in 1968 are given in table 4. Since gastric ulcer patients were older than control subjects, a direct adjustment for age was made. The only statistically significant difference between patients and controls was that in 1968 duodenal ulcer patients were more

;t::... TABLE 3. Percentages of duodenal ulcer patients and control subjects smoking cigarettes at four ages, by age at diagnosis Age at diagnosisa Age <20 2()-29 3{)-44 45-59 ~ 6 0 Percentage smoking'> Percentage smoking Percentage smoking Percentage smoking Percentage smoking Patient Control Patient Control Patient Control Patient Control Patient Control - - - -- - - - -- 20 60.0 (20) 30.0 (20) 52.1 (119) 47.0 (149) 52.5 (181) 37.6 (197) 52.4 (103) 31.9 (119) 51.7 (29) 40.0 (45) ------ - - - -- 30 52.6 (19) 57.9 (19) 55.2 (116) 51.4 (138) 68.5 (181) 54.3 (197) 70.9 (103) 53.8 (119) 69.0 (29) 55.6 (45) - - - -- - - - -- 45 40.6 (69) 38.2 (76) 51.6 (157) 38.7 (163) 61.8 (103) 47.9 (119) 58.6 (29) 48.9 (45) - - - -- - - - -- 60 20.0 (20) 31.8 (22) 40.0 (55) 20.4 (49) 32.1 (56) 22.4 (67) 44.8 (29) 37.8 (45) - - - -- - - - -- Average age smoking 19.3 20.6 18.5 18.9 19.6 20.9 19.7 21.1 21.3 20.4 started Average age in 1968 41.7 41.5 46.5 45.0 54.7 53.1 59.8 60.0 70.9 72.5 a Percentages above the dashed line represent smoking habits prior to diagnosis. Numbers in parentheses are total numbers of physicians living at each age. b No percentage indicates 10 physicians or fewer living.

342 MONSON Vol. 68, No.!J TABLE 4. Relation between body form and peptic ulcer Group No. Average age Average height Average weigh t Ponderal index At age 21 I In 1968 At age 21 In 1968 inches 16 Duodenal ulcer patients... 412 54.6 69.38 154.3 170.9 12.98 12.54}* Control subjects... 484 53.9 69.27 155.4 173.4 12.93 12.46 Gastric ulcer patientsa... 50 56.8 69.66 160.1 174.8 12.88 12.48 a Age adjusted to the age distribution of the control subjects. All comparisons of height, weight, and ponderal indices between cases and controls are not statistically significant except when noted: *, P < 0.02. TABLE 5. Relation between cigarette smoking, body form, and duodenal ulcera Group No. Average age Average height Average weight Ponderal index At age 21 I In 1968 At age 21 In 1968 inches 16 Duodenal ulcer patient smokers (A)... 297 55.0 69.36 154.4 170.3 12.98 12.55 Duodenal ulcer patient nonsmokers (B)... 115 53.7 69.42 154.1 172.4 12.99 12.51 Control subject smokers (C).. 297 53.8 69.46 156.5 173.0 12.94 12.50 Control subject nonsmokers (D)... 187 54.0 68.98 153.7 174.1 12.93 12.39 a The average age, height, weights, and ponderal indices were compared for the following combinations of groups using the Student's t-test: (A + C, B + D), (A, B), (C, D), (A, C), (B, D). The only statistically significant differences were for two ponderal indices in 1968. Control subject smokers were more slender than control subject nonsmokers (C, D: P < 0.05) and all smokers were more slender than all nonsmokers «A + C), (B + D): P < 0.02). Comparisons between all duodenal ulcer patients and all control subjects «A + B), (C + D» are given in table 4. slender than controls, as shown by their higher ponderal index. If a direct adjustment is made for smoking habits, the adjusted ponderal index for duodenal ulcer cases of 12.53 is still greater than that for control subjects (P < 0.05). The interaction of smoking and body form with duodenal ulcer is presented in table 5. There were no differences between the four ulcer-smoking groups with respect to height, weight, or pond era I index at age 21 and weight in 1968. In 1968 control smokers were more slender than control nonsmokers and all smokers were more slender than all nonsmokers. The average weight gained between age 21 and the time of the study was as follows: smoking ulcer patients gained 15.9 lb, smoking control subjects gained 16.5 lb, nonsmoking ulcer patients gained 18.3 lb, and nonsmoking control subjects gained 20.4 lb. There is little difference in the average ages of these four groups. Discussion That there is an association between cigarette smoking and peptic ulcer cannot be doubted. In all studies, smokers have more ulcers than nonsmokers. Further, among ulcer patients, those who smoke have a higher rate of morbidity and mortality than those who do not. But the question still remains as to whether smoking is a cause of ulcer. It might be supposed that, if smoking were a cause, heavier smokers would be at greater risk. The study of Doll et a1.6 and the present study have not found an excess of heavy smokers in those with ulcer. Furthermore, the smoking habits of those

March 1970 SMOKING AND BODY FORM IN ULCERS 343 who eventually develop an ulcer seem to be determined by age 20. Even that group which did not develop a duodenal ulcer until after age 60 was smoking already in a greater percentage at age 20 than was expected based on control subjects. If smoking had an acute effect on the gastrointestinal tract, one might expect to see a relative increase in the percentage who smoked immediately prior to the diagnosis of the ulcer. The finding that physicians with duodenal ulcer started smoking at an earlier age than control subjects, but did not smoke longer or stop less often, adds credence to the theory that cigarette smoking is not a direct cause of duodenal ulcer. It seems more likely that whatever causes a person to smoke also is important in the future development of an ulcer. Since there were so few physicians with gastric ulcer, it is difficult to differentiate between their smoking habits and those of physicians with duodenal ulcers. More gastric ulcer patients had smoked and there is a suggestion that they were heavier smokers. However, they did not start at an earlier age in contrast to the findings of Doll and his co-workers.6 The anthropometric data presented are recognized to be minimal. Also, the recall of one's weight at age 21 undoubtedly is somewhat inaccurate.21 However, the results in table 4 that show duodenal ulcer patients to have a higher ponderal index than control subjects at the time of the study in 1968 make one ask whether the previously reported linearity in ulcer patients is a result of the disease. The average height, weight, and ponderal index at age 21 for duodenal ulcer patients and control subj ects are essentially the same. Gastric ulcer patients were almost 5 lb heavier on the average than control subjects at age 21, but this difference is not statistically significant. No support can be found in these data for the contention that persons who smoke differ in body form from those who do not smoke. It seems likely that the higher ponderal indices in 1968 for control and all smokers relative to the corresponding nonsmokers result from smoking. As seen in table 5, smokers gained less weight than nonsmokers and duodenal cases gained less than controls, with smoking being less conducive to weight gain than ulcer. Physicians are known to be smoking far less now than in the past.22, 23 Of Massachusetts physicians who once smoked cigarettes, 60% have stopped. Also, a greater number of younger physicians are stopping.24 Results of the survey of the total physician population suggest that the incidence rate of duodenal ulcer also has been decreasing in those under age 45 over the past 10 to 20 years.20 Whether these two trends are related cannot be determined from the present data. A repeat survey in perhaps 10 years would be important in gaining insight into the association between cigarette smoking and peptic ulcer. REFERENCES 1. Barnett, C. W. 1927. Tobacco smoking as a factor in the production of peptic ulcer and gastric neurosis. Boston M ed. Surg. J. 197: 457-459. 2. Trowell, O. A. 1934. The relation of tobacco smoking to the incidence of chronic duodenal ulcer. Lancet 1: 808-809. 3. Gray, 1. 1929. Tobacco smoking and gastric symptoms. Ann. Intern. Med. 3: 267-277. 4. Jamieson, R. A., C. F. W. Illingworth, and L. D. W. Scott. 1946. Tobacco and ulcer dyspepsia. Brit. M ed. J. 2: 287-288. 5. Batterman, R. C., and Ehrenfeld,!. 1949. The influence of smoking upon the management of the peptic ulcer individual. Gastroenterology 12: 575-585. 6. Doll, R., F. Avery Jones, and F. Pygott. 1958. Effect of smoking on the production and maintenance of gastric and duodenal ulcers. Lancet 1: 657-662. 7. Kasanen, A., and J. Forsstroem. 1966. Social stress and living habits in the etiology of peptic ulcer. Ann. Med. Intern. Fenn. 55: 13-22. 8. Edwards, F., T. McKeown, and A. G. W_ Whitefield. 1959. Association between smoking and disease in men over sixty. Lancet 1: 196--200. 9. Doll, R., and A. B. Hill. 1964. Mortality in relation to smoking: 10 years' observation of British doctors. Brit. M ed. J. 1: 1399-1410, 1460-1467. 10. Kahn, H. A. 1966. The Dorn study of smoking and mortality among U. S. veterans: report on eight and one-half years

344 MONSON Vol. 58, No.3 of observation, 1-125. In W. Haenszel [ed.], Epidemiological approaches to the study of cancer and other diseases. National Cancer Institute Monograph No. 19. United States Public Health Service, Bethesda. 11. Hammond, E. C. Smoking in relation to the death rates of one million men and women, 127-204. In W. Haenszel [ed.], Epidemiological approaches to the study of cancer and other diseases. National Cancer Institute Monograph No. 19. United States Public Health Service, Bethesda. 12. Fisher, R. A. 1959. Smoking-the cancer controversy. Oliver & Boyd, Ltd., London. 13. Berkson, J. 1958. Smoking and lung cancer: some observations on two recent reports. J. Amer. Stat. Assn. 53: 28-38. 14. Lilienfeld, A. 1959. Emotional and other selected characteristics of cigarette smokers as related to epidemiological studies of lung cancer and other disease. J. Nat. Cancer Inst. 22: 259-282. 15. Eysenck, H. J., M. Tarrant, M. Woolf, and L. England. 1960. Smoking and personality. Brit. M ed. J. 1: 1456-1460. 16. Kanevsky, A. B. 1943. The constitutional aspects of peptic ulcer. Amer. J. Med. Sci. 206: 90-112. 17. Damon, A., and A. P. Polednak. 1967. Constitution, genetics, and body form in peptic ulcer. A review. J. Chronic Dis. 20: 787-802. 18. Seltzer, C. C. 1963. Morphologic constitution and smoking. J. A. M. A. 183: 639-&15. 19. Peters, J. M., and B. G. Ferris. 1967. Morphologic constitution and smoking. A further evaluation. Arch. Environ. Health (Chicago) 14: 678-681. 20. Monson, R. R., and B. MacMahon. 1969. Peptic ulcer in Massachusetts physicians. New Eng. J. Med. 281: 11-15. 21. Damon, A. 1965. Adult weight gain, accuracy of stated weight, and their implications for constitutional anthropology. Amer. J. Phys. Anthrop. 23: 306-311. 22. Snegireff, L. S., and O. M. Lombard. 1959. Smoking habits of Massachusetts physicians. New Eng. J. Med. 261: 603-604. 23. Phillips, A. J., and R. M. Taylor. 1968. Smoking habits of physicians in Canada. Canad. Med. Assn. J. 99: 955-957. 24. Monson, R. R. 1970. Cigarette smoking in Massachusetts physicians-1968. New Eng. J. M ed. In press.