Document zzgLxKZXRMQmkbMkoLbQGQMd0

FILE NAME: Smoking (SMOK) DATE: 1944 DOC#: SMOK029 DOCUMENT DESCRIPTION: Journal Article - The Epidemiology of Cancer Vol. 34 33 to . U The Epidemiology of Cancer From the Viewpoint of the Health Officer* MORTON L. LEVIN, M.D., Dr.P.H., F.A.P.H.A. Assistant Director, Division of Cancer Control, New York State Department of Health, Albany, N. Y. ACTIVITIES in cancer control by be of value in the application of cancer public health agencies need not control measures. The health officer and usually do not rest upon the recog who is interested in cancer control must nition of any epidemiological peculi also take stock of the modern advances arities of the disease, in the strict sense in the etiology of cancer and inquire of that term. The necessity for per whether these now have any practical suading people who have symptoms to significance in the control of human seek medical care without delay, as cancer. well as the desirability of making it To review broadly the salient features easy for them to secure prompt diag regarding the occurrence of cancer in nosis and adequate treatment, are suffi man, the facts to be considered may be ciently well defined to furnish a secure classified under four general headings: foundation for public health action. (1) environmental or exogenous agents I t is recognized that to accomplish these causing cancer; (2) the association of objectives with some degree of com cancer with other diseases; (3) evi pleteness is an undertaking of consider dences regarding intrinsic or constitu able magnitude, particularly if all tional factors affecting cancer incidence; persons who reach adult age must and (4) certain aspects of differential- be included in the scope of the cancer mortality. program. It should be stated at the outset Because the task of reaching the that cancer of different parts of the entire adult population with any type body and of different pathological of control measure is manifestly great, character in the same part are different the health officer who plans a cancer diseases. Although for some purposes control program seeks to make the it is useful to consider all types of limited forces he can throw into the cancer together, throughout this dis field count for more than may be cussion differences in etiology and in expected of random action directed epidemiological features according to to the public at large. From experience site of cancer will appear. in the control of infectious disease it is evident that information regarding what people are most apt to develop cancer or certain kinds of cancer would * Presented before the Health Officers Section of the American Public Health Association at the Seventy-second Annual Meeting in New York, N. Y., October 12, 1943/ Si-'i'P1I SiMi tVi.t T' ft: 612 American Journal of Public H ealth June, 1944 tumors. In human cancer such agents have been identified chiefly in the small group of occupational cancers. The first such observation was made in England in 1775 by Percival P o tt1 who noted in chimney sweeps a greatly increased incidence of scrotal epitheli oma, caused by exposure to soot or some chemical contained in soot. The substances or agents now known to cause cancer in man include arsenic, tar, pitch, paraffin, petroleum oils and derived products, benzol, aniline dye compounds, roentgen rays, radium rays and ultra-violet rays, possibly asbestos, nickel carbonyl and chromates. What common property of these diverse chem icals and radiations makes them poten tially carcinogenic is not clear; possibly all act by interfering with cellular enzymes, as the work of Rhoads 2 sug gests. Most of these agents produce skin cancer. Aniline dye compounds cause chiefly cancer of the bladder; excessive exposure to radium salts has been known to cause bone sarcoma and carcinoma of the lung; leukemia may follow chronic benzol poisoning. With but few exceptions, the carcinogenic effect of these agents has been demon strated in experimental animals as well as in man. A survey of occupations listed3 according to exposure to various hazards shows 146 different occupations in this country in which exposure to known carcinogenic agents may occur. How ever, the number of reported occu pational cancers is quite small. Hueper 4 estimates that the total cases reported in the world literature is from 8,000 to 9,000, of which approximately 400 have been reported from the United States. A partial explanation for the small number of reported cases of occupa tional cancer may be' the fact that, although the period of exposure neces sary to produce cancer may be as little as one year, the time from such expo sure until the appearance of the tumor may be as long as 30 years, averaging for some agents approximately 16 years, so that the tumor may not appear until long after the worker has changed his occupation. There is also a natural reluctance on the part of industrial management to release information on occupational cancer. Although pre ventive measures, including periodic ex aminations, have been adopted in some plants, especially in the aniline dye industry, often the hazards are not recognized or not properly guarded against. Exposure to aniline dye com pounds occurs not only in the dye industry but in many others, including plants handling rubber and chose man ufacturing explosives. It is probable that the number of occupational cancers is greater than indicated by identified cases and that the enormous expansion of certain industries may further in crease this number in the future. Obviously, exposure to the carcino genic chemicals and radiations need not be occupational. Arsenic cancer of the skin has been observed following prolonged medicinal administration of Fowler's solution and, in the Argentine, from drinking water contaminated by arsenic ores. The influence of ultra violet radiation is believed responsible for the higher general incidence of skin cancer in the South as compared with the North in this country, as well as for its high incidence among out door workers in the North. The relationship of carcinogenic chemicals and radiations to the common run of malignant tumors in man is a matter of speculation. It has been suggested that part of the increase in cancer mortality of modern times may be attributable to the increased exposure. to such substances accom panying the industrial age. The diffi culties in the way of testing such a . hypothesis may be '"appreciated from the fact that a chemically induced H ealth June, 1944 e appearance of the tumor ong as 30 years, averaging nts approximately 16 years, tumor may not appear ter the worker has changed <n. There is also a natural ,n the part of industrial to release information on cancer. Although preures, including periodic exlave been adopted in some dally in the aniline dye ten the hazards are not >r not properly guarded josure to aniline dye comrs not only in the dye in many others, including ng rubber and those mancplosives. It is probable ber of occupational cancers an indicated by identified it the enormous expansion idustries may further in umber in the future, exposure to the carcino sis and radiations need pational. Arsenic cancer is been observed following idicinal administration of lion and, in the Argentine, a water contaminated by The influence of ultraon is believed responsible ier general incidence of n the South as compared ih in this country, as well gh incidence among cutin the North. ionship of carcinogenic radiations to the common lant tumors in man is a jeculation. I t has been it part of the increase irtality of modern times butable to the increased such substance* accomndustrial age. The diffi way of testing such a ay be * appreciated from t a chemically induced Vol. 34 E pidemiology of Cancer 613 tumor does not differ histologically from one arising in the same organ apparently spontaneously, and that such a tumor may appear long after the chemical agent has been eliminated from the body. We may anticipate that a great deal of future investigations on the causes of cancer in man will center on the possible presence of chemical carcino gens in food, water, and dust. Although the significance of the known carcino genic agents in the etiology of the vast majority of human cancers is at present unknown, continued medical observa tion of workers exposed to carcinogenic agents, even after they have left the employment where such exposure oc curred, is clearly indicated. This is rarely done now and presents a field for possible public health action. DIFFERENTIAL CANCER MORTALITY AMONG SOCIAL-ECONOMIC GROUPS In addition to the small group of identified occupational cancers, a con siderable array of statistical evidence points to increased mortality from cer tain forms of cancer in those economic groups among which industrial workers are largely found. Stevenson 5 analyzed cancer mortality statistics for males in England and Wales on the basis of social-economic class, dividing the population into pro fessional workers, skilled workers, un skilled workers, and two inter mediate groups. A progressive in crease ' in cancer mortality was found in each " lower " social-economic group. This increase was confined to cancer of the skin, lip, larynx, and the ali mentary canal from mouth to pylorus. For these sites, the standardized rates in unskilled workers was twice that of professional workers. In married women, classified by husband's occupation, a similar though less marked relationship appeared for the same sites of cancer and also for cancer of the uterus, indi cating that factors other than those due directly to occupation must be considered in explaining these facts. In married women also, a reverse rela tion was found for cancer of the breast, ovary, and thyroid, in which the higher rates were in the higher classes. The same differences appeared among single females, classified by social-economic status. In this country, broadly similar findings have been reported by Knight and Dublin 0 in life insurance data, and by Whitney,7 for total cancer not sub divided according to site. In Massa chusetts, Lombard and Doering 8 found that the foreign born and those of foreign parentage had higher mortality rates for buccal cavity and stomach cancer, but not for other sites. They concluded that a sufficiendy close rela tionship exists between these nativity groups and the lower social classes of England to justify the opinion that eco nomic social conditions are a factor in the incidence of cancer. It is of interest that the first analysis of cancer mor tality by economic status in this country was made by Charles V. Chapin 9 on the mortality returns of Providence, R. I., for 1865. He found the rate twice as high in the lower as compared with the higher economic class. Greater diagnostic accuracy in the medical care available to the higher income groups does not readily explain these differences in cancer mortality in social classes for the reason that better diagnosis increases rather than decreases the total number of recorded cancers. Also the types of cancer, in which the differences are found include both easily diagnosed sites, such as the skin, and poorly diagnosed sites, such as the stomach. Moreover, one of the most accurately diagnosed forms of cancer, th at of the breast, shows opposite social selection to that observed for almost equally ' easily diagnosed sites, such as the lip, the buccal cavity, 614 American Journal of P ublic Health June, 1944 and the uterus. Better therapeutic results might explain lower mortality from skin and lip cancer in the higher economic groups, but not lower mor tality from esophageal and stomach cancer, and certainly not the higher mortality from breast cancer in these groups. The differences in cure rates for stomach cancer in the best clinics as contrasted with the average would be insufficient to account for differences in cancer mortality as pronounced as those observed. The findings with respect to the higher cancer mortality in unskilled and industrial economic groups are frequently cited as evidence that the living conditions of these groups in volve greater exposure to " exogenous carcinogens." Aside from specific occu pational carcinogens, we are unable to identify what these agents may be. Regardless of the explanations for the higher mortality from certain forms of cancer in unskilled and industrial workers, the need for concentrating attention on such groups in applying cancer control measures is evident. ASSOCIATION OF CANCER W IT H OTHER DISEASES I t has long been noted that cancer occurs more frequently than normal in tissues the seat of the so-called precancerous lesions. The evidence for significant association is often far from conclusive. Precancerous lesions have been described in the skin, lip, liver, mouth, bones, thyroid, gastrointestinal tract, breast, ovary, uterus, and vulva. The greatest number have been de scribed in the skin, where at least twenty-two different precancerous states are said to occur.10 I t should be noted that in most cases of cancer, a specific precancerous lesion cannot be identified. The subsequent incidence of cancer in persons with precancerous lesions varies greatly, from a few (xeroderma pigmentosum; erythroplasia of Queyrat) in which cancer always supervenes, to many in which it is only an occasional occurrence. For the most part, figures which are reported refer not to secon dary incidence but to frequency of association. Where secondary incidence is stated, the factors of age and duration of observation are usually not taken into account. For most precancerous lesions, the available information does not permit accurate estimation of the degree of increased risk of cancer which they carry. There is adequate evidence that in women with chronic cystic m astitis11 the subsequent incidence of breast can cer is from 2 to 10 times as great as the average. Epithelioma of the tongue occurs in syphilitic males about 5 times more frequently than would be expected normally, and recently there have been presented data 12 indi cating that a similarily high incidence of cervix carcinoma occurs in women who have had syphilis. Other con ditions apparently associated with sub sequent cancer which may be mentioned are multiple polyposis, with intestinal cancer; cirrhosis of the liver with primarv liver cancer; Paget's disease of bone with osteogenic sarcoma; atrophy of the buccal and esophageal mucous membranes, attributed to Vitamin B deficiency, with buccal and esophageal cancer. Rhoads 13 has stressed the fact that many of the precancerous lesions are atrophic in nature. This is in accord with the observations that in experi mental liver cancer produced by the carcinogenic chemical, butter yellow, atrophy of the liver cells precedes the development of cancer. Kensler and his associates14 have shown further that in experimental animals this proc ess can be prevented by supplying extra quantities of riboflavin and casein in the diet. From the standpoint, of cancer con trol, the existence of precancerous Vol. 34 E pidemiology of Cancer 615 lesions presents the possibility Of insti tuting case finding procedures to dis cover individuals having such lesions, to be followed by treatment where possible, and by continued observation so that if cancer develops, it may be treated early in its course. CONSTITUTIONAL FACTORS IN HUMAN CANCER Although certain of the precancerous lesions (leukoplakia, farmer's skin) are attributable to environmental agents, others such as familial intestinal poly posis and multiple neurofibromatosis are apparently the result of hereditary or at least familial influences. Further, even in the effects of identified exoge nous carcinogenic agents, the degree of inherent susceptibility or resistance probably plays a role, as is indicated by the many workers who, although exposed for long periods to carcino genic chemicals, do not develop cancer. As in most other diseases, both the constitutional factor and the environ mental must be considered in the etiology of malignant tumors. The information available concerning presumably constitutional factors affec ting cancer incidence in man comprises data on (1) hereditary forms of cancer or of benign tumors; (2) the occurrence of cancer families; (3) the familial incidence of cancer; and (4) the inci dence of secondary primary cancers in patients following successful treatment of first cancer. In a few rare tumors a hereditary mechanism is generally accepted, al though the effect of unknown environ mental factors cannot be excluded en tirely. Retinoblastoma of the eye occurs with sufficient frequency in sib lings and in descendants of cured patients to justify advice against mar riage or having more children. Examples of hereditary benign tumors are familial intestinal polyposis which occurs in one-third the children of affected fami lies and which becomes malignant in at least 25 per cent of cases; multiple neurofibromatosis which occurs in half the children if one parent is affected, and of which 13 per cent are reported to develop sarcoma; and certain benign bone tumors. In addition, there have been described " cancer families," in which cancer, often of the same organ, such as the breast, uterus, or stomach, occurred in several brothers or sisters. W hat pro portion of cancer patients come from such families is not known. With regard to the common forms of cancer, studies have been made to determine whether the parents and sib lings of cancer patients have any greater cancer mortality than the general popu lation. The majority of such studies do show increased mortality in both parents and siblings, ranging from 20 to 60 per cent higher than expected. When cancer occurs in the same family, there is also a definite tendency for it to appear in the same organ.13'20 I t should be noted that such findings do not necessarily indicate a general familial concentration of cancer, but could be accounted for by assuming that a relatively small percentage of cancer patients come from cancer fami lies. For example, in Crabtree's data,15 among 1,029 families there occurred an excess of 93 cancer deaths (37 per cent) over that expected in parents and siblings together. An increase above normal of one case in 9 per cent of the families would thus account for all of the observed excess of cancer deaths, with a normal incidence in" the remaining 91 per cent of families. I t is probably superfluous to point out that an increased familial incidence of cancer does not necessarily indicate that hereditary or genetic* factors are responsible, since similar environmental factors may also run in families. - The evidence regarding familial can cer, although far from conclusive, is 616 American J ournal of Public H ealth June, 1944 sufficiently impressive so that in some clinics a family history of cancer, par ticularly of the breast and uterus, is regarded as indicating need for in creased watchfulness for the possible development of a similar tumor in other members of the family. Certainly no objection will be raised to such an interpretation, which can lead only to increased chance of early diagnosis with correspondingly increased probability of successful treatment. Obviously, the time has not yet come to look upon the occurrence of cancer in one member of a family as the signal for examination and con tinued follow-up of the patient's broth ers and sisters. In identified cancer families this procedure is justified. Without further information, its em ployment in families where only one case has occurred would be experi mental. The principle is being applied by some physicians and clinics, but it has not reached the stage of public health practice. Related to the problem of the nature of inherent susceptibility to cancer is the question whether the development of cancer in one organ denotes an increased susceptibility to cancer in other parts of the body. This question has been approached by studying the subsequent incidence of other primary cancer in persons successfully treated for one malignant tumor. The subject has been investigated extensively by Peller,21 and more recently by Lombard and Warren.22 Their findings are sim ilar and indicate that the incidence of second cancer is not significantly differ ent from that of the general population. I t should be emphasized that the oppo site conclusion of Peller rests not on different findings but on the theoretical assumption that in cancer patients the subsequent expected incidence should be 5 times that of the- general popu lation. This is based on the further assumption that only 20 per cent of the population are susceptible to can cer and, consequently, that among can cer patients, who are susceptible, of course, the annual age-specific mor tality rates should oe S times that of the general population. There is no known method of determining suscepti' bility to cancer and no reason to assume that only those who develop cancer are susceptible. The available experi mental evidence indicates that environ mental factors can alter incidence markedly. From the practical standpoint the significant fact is that the incidence of second cancer in cancer patients is not greatly different from that of the general population. This suggests that increased susceptibility to cancer, what ever its nature, is not general but more probably is organ specific, as is the case in certain high tumor strains of mice and rats. The role of hereditary factors in the causation of human cancer and the extent to which such factors are modi fiable by environmen tal agents, remains obscure. There seems little doubt that such factors do exist for some tumors and in some families, but the available evidence indicates that they are of only minor importance in the majority of cases. DIFFERENTIAL MORTALITY FROM CANCER The known facts regarding the eti ology of cancer, fragmentary as they are, can be correlated with only a few of the differential characteristics of cancer mortality. These characteris tics, however, have intrinsic interest from the standpoint of a control program. Although great stress has been laid on the errors of diagnosis inherent in mortality statistics of cancer, many of the differences in cancer mortality observed in different population groups are not . readily' explainable by diag nostic error... The extent to which ,TH Jumz, 1944 susceptible to can dy, that among can- are susceptible, of tl age-specific mor- be 5 times that of ition. There is no ietermining susceptr : no reason to assume A'ho develop cancer 'he available experidicates that environan alter incidence ical standpoint the that the incidence n cancer patients is at from that of the This suggests that ility to cancer, whatiot general but more specific, as is the 'h tumor strains of ditary factors in the an cancer and the ch factors are modintal agents, remains ms little doubt that ist for some tumors es, but the available hat they are of only in the majority of 'ALITY FROM CANCER s regarding the etiragmentary as they ted with only a few ! characteristics of These characterise intrinsic interest tint of a control dress has been laid diagnosis inherent ics of cancer, many in cancer mortality it population groups cplainable by diagextefit to which Vol.34 E pidemiology of Cancer 617 diagnostic errors are responsible for differences in mortality in different pop ulation groups must be considered separately for each group and each site of cancer where such differences are found. TREND OF CANCER MORTALITY The continued upward trend of can cer mortality has made cancer one of the major health problems of our time. One-third of the increase in mortality is due to increased " aging " of the population. The remaining increase is sometimes written off as reflecting in creased recognition of cancer rather than increased incidence. In upstate New York, comparison of age-standardized mortality from 1931 to 1941 shows an increase during this period of 10 per cent in male mortality; and a decrease of 6 per cent in female mortality. Mortality from cancer of the buccal cavity, skin, and lip, has decreased slightly in both sexes. Death rates from cancer of the stomach and the liver have decreased significantly in both sexes. Cancer of the breast increased only slightly; mortality from uterine cancer decreased by approxi mately 16 per cent. The increase in mortality from certain types of cancer in males is sufficient to raise the total mortality above that in the earlier period. The most marked increase occurred in cancer of the lungs and other respiratory organs, mortality from which increased threefold in males but only slightly in females. In females the decline in certain sites, notably the stomach, the liver, and the uterus, more than offsets the increased rate for other types of cancer. Since there is no reason to believe that diagnostic accu racy lessened during the past decade, it is probable that this decrease fore shadows a continued downward trend in cancer mortality among women. From data regarding hospitalization of cancer cases and proportion of diag noses verified by pathological exami nation, there is no reason to believe that, for the same site of cancer, diag nostic accuracy is different in the two sexes. For this reason, as Gover has pointed out, the more rapid increase in mortality for certain internal types of cancer in males than in females is probably real and not due entirely to improved diagnosis. CANCER MORTALITY BY COLOR AND GEOGRAPHIC REGIONS IN TH E UNITED STATES The possible association of cancer of the buccal cavity and of the liver with certain dietary deficiencies and the association of tongue cancer and probably cervix cancer with preexisting syphilis suggest that mortality statis tics in this country might reflect corre sponding differences for cancer of these sites between geographic sections _and between white and colored. For ex ample, we might expect a relatively high mortality from buccal and liver cancer in those southern states with widespread gross dietary deficiency as indicated by high mortality from pel lagra; also, colored males would be expected to have a higher mortality from tongue cancer; and colored females from cancer of the cervix. Govers data 24 for the years 1930 to 1932 show that age-standardized mor tality from total cancer in both sexes in this country is highest in the North east and on the Pacific coast, lowest in the South and Southwest. The only exceptions are cancer of the skin, which is highest in the South, and cancer of the mouth and pharynx, which is highest in southern females and second highest in southern males. All other forms of cancer, including cancer of the liver and biliary passages, show lower rates in the South. These rela tive differences in site distribution of cancer between North and South appear in hospital deaths as"'-well as in all 618 American Journal of Public H ealth June, 1944 recorded deaths. The differences, how ever, are not so marked in morbidity data. The expected difference in can cer mortality in the South is thus present for buccal cavity cancer but not for cancer of the liver. Comparison between white and col ored cancer mortality in the United States shows that for most forms of cancer, colored mortality is lower than among whites. The differences are less marked in the North than in the South, presumably due to the fact that Negroes in the North obtain better medical care. A peculiar feature of cancer mortality in Negroes is that it is lower only in the age groups above 54 years; in younger age groups it is as high or slightly higher than among whites. Mortality from tongue cancer is lower in colored females, and only slightly higher in colored males than in whites. The forms of cancer showing; markedly higher mortality in the colored race are cancer of the external genitalia in males, and of the uterus and other female genital organs in females. The excess mortality from cancer of the uterus among colored women is 75 per cent in the South and 91 per cent in the North, and is sufficient to bring total cancer mortality among colored females slightly above that among whites in both sections of the country. In the experience of the Metropolitan Life Insurance Company's industrial de partment 25 from 1917 to 1935, the age-standardized mortality from uterine cancer among colored females was 55 per cent higher than among whites. We do not as yet have mortality data for cancer of the cervix uteri separated from that of the uterine fundus, but it is known that approximately 85 per cent of uterine cancers arise in the cervix. The expected differences in cancer mortality between white and colored races because of the apparent associ ation of tongue and cervix cancer with syphilis are not found for tongue can cer, but are for uterine cancer. Obvi ously, such a finding is merely cor roboratory and does not establish the fact of an association between syphilis and uterine cancer. Regardless of its cause, the markedly high mortality from uterine cancer among colored females deserves greater attention than it has received, both from the standpoint of investigation and from that of administration of cancer control programs. Cancer of the uterus and of the breast and ovary occur also with dif ferent frequency among women of differ ent marital status. Uterine cancer mortality is highest among married women, while breast and ovarian cancer mortality is higher among single women. The mortality from breast cancer among childless married women is as high as in single women. The higher mor tality from breast cancer among single women and childless married women is usually attributed to the absence of normal lactation, while the higher mor tality from uterine cancer in married women has been interpreted as evidence that injuries resulting from childbirth are causes of uterine cancer. These interpretations have not been fully established. Recent data from Aus tralia, described by Dorn.26 indicate that uterine cancer mortality is highest among married women who have never borne children. A more complete review of the differ ential mortality of cancer is not within the scope of this paper. It may be said, however, that most of the major forms of cancer exhibit sufficiently' dif ferent epidemiological characteristics to indicate that each must be approached as a separate problem in cancer control. SUMMARY. AND DISCUSSION In summary, there, is evidence that the occurrence of human cancer is in Vol. 34 E pidemiology of Cancer 619 some cases attributable to the influence of specific chemical and physical agents; in others to an association with precancerous lesions and with other diseases; and, in a relatively small number of cases, familial factors, which may be hereditary, are operative. In a large proportion of cases, none of these etiologic factors can be identified. Con siderable differences appear in mortality from various forms of cancer in persons of different race, economic status, and marital status. Most of these differ ences are not readily explainable by any single hypothesis regarding the causation of cancer. Many of the etiological and differ ential factors discussed point to possible public health applications in the form of special attention in education, in case finding and in follow-up directed to the groups which have an apparently high mortality and incidence of certain forms of cancer. Examples of such groups are: industrial and unskilled workers (cancer of the skin, lip, mouth, larynx, and stom ach); unmarried women (cancer of the breast); syphilis patients (cancer of the vulva, cervix, tongue); Negro women (cancer of the uterus). The experience of the Strang Cancer Prevention Clinic in New York City, in case finding among apparently healthy women, indicates that the pro portion of early cancer cases found is comparable to that of early cases of tuberculosis discovered by mass x-ray examinations.27 Active case finding ap plied to groups with higher than normal incidence of cancer may be correspond ingly more effective. It seems reasonable to forecast that, in the future, cancer control programs will be guided to a greater extent than in the past by existing knowledge and by further investigation of the epidemi ological characteristics of the disease. These point to a logical development of control activities directed toward population groups which apparently stand in greatest need of such measures and among which they should prove most fruitful. REFERENCES 1. Pott, Percival. Cktrurgical Observations. Hower, Clarke & Pollins, London, 1775. 2. Rhoads, C. P. Recent Studies in the Produc tion of Cancer by Chemical Compounds, the Con ditioned Deficiency as a Mechanism. Bull. New York Acad. Med., 18:53-64 (Jan.), 1942. 3. Dublin, L. I., and Vane, R. J. Occupation Hazards and Diagnostic Signs. Bull. No. 582, U. S. Bureau of Labor Statistics. Washington, 1933. 4. Hueper, W. C. Cancer in Its Relation to Occu pation and Environment. Bull. Am. Soc. Control Cancer, 25:63 (June), 1943. 5. (a) The Registrar-General's Decennial Supple ment, England & Wales, 1921. Part II. Occupa tional Mortality, Fertility and Infant Mortality. London, 1927. (b) The Registrar-General's Decennial Supple ment, England & Wales, 1931. Part Ila. Occupa tional Mortality. London, 1938. 6. Knight, Augustus S., and Dublin, Louis I. The Relation of Cancer to Economic Condition. Metro politan Life Ins. Co., New York, 1917. 7. Whitney, Jessamine S. (ed.). Death Rates by Occupation. Nat. Tuberc. Assoc., New York, June, 1934. 8. Lombard, H. L., and Doering, Carl R. Cancer Studies in Massachusetts. III. Cancer Mortality in Nativity Groups. /. Prev. Med., 3:343, 1929. 9. Chapin, Charles V. Deaths among Tax-payers and Non-taxpayers, Income Tax. Providence, 1865. A.J.P.H., 14:647 (Aug.), 1924. 10. Mackee, George M., and Cipollaro, Anthony C. Cutaneous Cancer and Precancer. New York. Am. J. Cancer, 1937. 11. Warren, Shields. The Relation of " Chronic Mastitis " to Carcinoma of the Breast. Surg., Gynec. & Obst., 7:257-273 (Sept.), 1940. 12. Levin, Morton L., Kress, Louis C., and Gold stein, Hyman. Syphilis and Cancer. New York State J. Med., 42:1737 (Sept. 15), 1943. 13. Rhoads, C. P. Precancerous Lesions. Bull. Am. Soc. Control Cancer, 25:5-7 (Jan.), 1943. 14. Kensler, .C. J., Sugiura, K., Young, N. F., Halter, C. R., and Rhoads, C. P. Partial Protec tion of Rats by Riboflavin with Casein against Liver Cancer Caused by Dimethylaminoazoberizene. Science, 93:308, 1941. 15. Crabtree, James A. Observations on the Familial Incidence of Cancer. A.J.P.IL, 31:49 (Jan.), 1941. 16. Deelman, H. J. Heredity and Cancer. Ann. Surg., Jan., 1931, pp. 30-34. 17. Wassink, W. F. Cancer et Heredite. Genetica, 17:103-144, 1935. 18. Waaler, H. M. Ueber die Erblichkeit des Krebses. Oslo/ 1931. 19. Wainwright, J. M. Breast Cancer in Great Britain and America. Am. J. Cancer, 15, 4:2610, 1931. ' - 20. Lombard, H. L. Studies on Familial Aspects of Cancer. New Eng. J. Med., 218:711-713 (Apr. 28), 1938. 21. Peller, Sigismund. Metachronous Multiple Malignancies in 5876 Cancer Patients. Am. J. Hyg., 34, 1, Sec. A--1-11 (July), 1941. 22. Lombard, H. L., and Warren, Shields. As sociation of Other Malignant Tumors with Cancer of the Skin. A.J.P.H., 33:533-536 (May), 1943. 23. Pohlen, Kurt, and Emerson, Haven. Errors in Clinical Statements of Causes of Death. A.J.P.H., 32: 251-260 (M ar.), 1942. 620 .. American Journal of Public Health June, 1944 24. Gover, Mary. Cancer-Mortality in the United States. I. Trend of Recorded Cancer Mortality in the Death Registration States of 1900 from 1900 to 1935. Pub. Health Bull. No. 248, U. S. Public Health Service, Washington, 1939. II. Recorded Cancer Mortality in Geographic Sections of the Death Registration States of 1920, from 1920 to 1935. Pub. Health Bull. No. 252, U. S. Public Health Service, Washington, 1940. III. Geographic Variation in Recorded Cancer Mortality for Detailed Sites for an Average of the- Years 1930-32. Pub. Health Bull. No. 257, U. S. Public Health Service, Washington, 1940. 25. Dublin, L. I., and Lotka, A. J. Twenty-five- Years of Health Progress. Metropolitan Life In surance Co., New York, 1937. 26. Dorn, Harold E. Cancer and Marital Status. Human Biol., 15, No. 1 (Feb.), 1943. 27. Memorial Hospital, New York City. Annual Report, 1942. U. S. Cadet Nurse Corps Induction Pledge At this moment of my induction into the United States Cadet Nurse Corps of the United States Public Health Service: I am solemnly aware of the obligations I assume toward my country and toward my chosen profession. I will follow faithfully the teachings of my instructors and the guidance of the physicians with whom I work; I will hold in trust the finest traditions of nursing and the spirit of the corps; I will keep my body strong, my mind alert, and my heart steadfast; I will be kind, tolerant and understanding; Above all, I will dedicate myself now and forever to the triumph of life over death. As a Cadet Nurse, I pledge to my country my service in essential nursing for the duration of the war.