portant in the epidemiology of gastric cancer: (1) Gastritis and polyps. (2). Diet and nutrition. (3) Hereditary and genetic factors. (4) Stress and emotional factors.
The Epidemiology Walter
B. Quisenberry,
of Gastric
M.D.
Cancer of the stomach is one of the most prevalent types of cancer in the world today and it is one of the most difficult types to detect during the early stage. Therefore, it is expedient to hasten studies aimed at finding the causes and thus, if possible, make it preventable. The epidemiology of gastric cancer is not definitely known. This report will deal with theories and studies designed to find out more about it. Although it has been shown conclu sively that certain ethnic groups have a higher incidence of gastric cancer than other groups3' 4. 7. 8. 10,11,13 the epidemio logic principles involved are probably similar in all people. Ethnic or racial dif ferences may be due to environment or heredity or a combination of both, along with behavior patterns which may cause tissue susceptibility. In this report, attention will be given to the following areas that may be im portant in the epidemiology of gastric cancer: (1) Gastritis and polyps. (2) Diet and nutrition. (3) Hereditary and genetic factors. (4) Stress and emotional factors. (5) Oral health. (6) Occupation. Gastrit is and Polyps There are several forms of gastritis and the etiology of all types seems to be un certain. Strode4 has studied the hyper trophic type and believes that it is from two to two and one-half times as frequent in Japanese men in Hawaii as it is in other men. He has pointed out also that gastric cancer is correspondingly high in this ethnic group. These observations seem to indicate a relationship between the two conditions. Strode'4 has pointed out that polyps of the stomach are recognized as precancer Hawaii
154
Cancer
Society,
Honolulu,
Cancer
Hawaii.
ous and that hypochlorhydria is a com monly associated finding. He states further that in cases of marked hypertrophy of the gastric mucosa, it is usual to find a deficiency in secretion of hydrochloric acid. These observations strongly suggest that gastric mucosal hypertrophy may pre dispose to malignancy. The following case record illustrates how hypertrophic gastritis may develop, appear on roentgenogram, and be either followed by or accompany gastric cancer: A 48-year-old Chinese woman was first seen by her private physician on November 30, 1956, because of profuse gastric hemorrhage. She gave a history
of intermittent attacksof epigastric pain lasting approximately one week which had occurred about every two months during the past three to four years. She had treated herself with a bland diet and bicarbonate of soda. She had been symptom-free between at tacks and there had been no weight loss. Roentgenograms of the stomach, taken December 1, 1956, showed an extensive hypertrophic gastritis (Fig. I). She was treated for two months with antacids, anticholinergics, and a bland diet. Stomach roentgenograms were then repeated and showed some clearing of the gastritis, but an area was seen on the lesser curvature of the stomach which was considered a pos sible ulcer. On March 8 and March 16, 1957, cytologic examinations of gastric secretions were performed using the chymotrypsin technique. Cells suspi cious of malignancy were found on both examinations (Fig. 2). On March 28, 1957, a partial gastrectomy was per formed. On gross examination of the surgical specimen, an ulcerated area I cm. in diameter and 2 mm. in depth was found on the lesser curvature. The opened stomach is shown in Fig. 3. On histologic examination of the ulcerated area, an anaplastic adenocarcinoma. with focal penetration of the wall and superficial spread, was seen (Fig. 4).
Figure I. Extensive hypcrtrophic 1@@ @
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Figure 2. Cells suspicious gastric secretions. (840X)
of cancer
in
Figure 4. Microscopic section of stomach showing anaplastic adenocarcinoma. (265X)
Figure 3. Gross specimen of stomach re moved at surgery (ulcer not visible).
155
Allperigastric lymph nodesremovedat ease (primarily a chronic iron deficiency) operation werefoundfreeofcanceron to cancer of the alimentary tract. He states histologic examination. It cannot be “¿that in addition to irondeficiency, defi saidwithcertainty thatthehypertrophicciencies of other nutrients may be of addi
gastritis
in this case was precancerous
norhasitbeenshown definitely thatthe gastritis predisposed to malignancy. It seems quite definite, however, that the gastritis either preceded or accom panied the cancer. The cause of the gas tritis is not known but possible etiologic factors which may be also involved in
tional importance.― This seems to be con sistent with the possibility that diet and nutrition may be important in predispos ing to, if not being an epidemiological fac tor in causing, cancer of the stomach.
Strode― points outthathypoproteinemia and achlorhydria have not infrequently
theepidemiology of gastric cancerare been found to be associated with hyper discussed below. trophic gastritis. Studies todetermine the cause
of the hypoproteinemia
have
not
beenenlightening, according toStrode. He
Diet and Nutrition
states “¿it has been suggested that a sub by the gastric mucosa which exerts an inhibitory influence on
The partwhichmay be playedby diet stance is produced and nutrition in the epidemiology of gas tric cancer has not been definitely deter mined but studies are being conducted in Hawaii in an effort to evaluate this.
thesynthesis or storage of protein or that plasmamay be lostthroughtheabnormal mucosa into the gastric lumen.― From the
Many of theoriental peopleinHawaii data at hand Strode believes there may be gas (especially thosein theolderage brack a relationship between hypertrophic tritis andgastric cancer. Itmay bepossible ets) eat diets peculiar to their own ethnic groups. This is probably
more particularly
that a diet which is low in protein plays a
of hypertrophic gas trueofJapanesepeoplethanitisofothers. partin theetiology JapaneseinHawaiieatlargeamountsof tritis and gastric cancer which may follow. white rice which is low in vitamin B1 con tent and raw fish which has been shown to contain thiaminase which inactivates vita min B1.5 It has been saown that people who consume large amounts of carbohy drate need a vitamin B1 intake higher than average.5 Tea is usually taken with the rice and fish and is usually very hot. At times
The primary
factors then, so far as diet
andnutrition areconcerned ingastric can cerepidemiology, arethelow vitaminB1 intake,
low protein
consumption,
and an
interference withironmetabolism. These mightwellgivea chronicirondeficiency and hypoproteinemia. The heatof food and drinkmay alsobe important.
hotsakeisalsoconsumedwiththefood. Pickle made from vegetables isalsoeaten Hereditary and Genetic Factors with the other foods. This type of diet which contains little protein other than fish is quite popular among the older Jap anese people. Younger Japanese usually eat more vegetables and meat other than
Airdand Bentall' haveshown thatcan cer of the stomach
is most frequent
in
bloodgroupA and least frequent inblood group 0. A study is being conducted
in
Hawaiiinan effort todetermine whether fishthando theolderpeople. Ivy found thatsome persons(10 per there might be any hereditary predisposi in cent)couldtakefood and drinkso hot tion or evidence of gene-connected fluence in cancer of the stomach as may be shown in blood grouping, diabetes, in becausecancermay occurin burn scars herited intestinal conditions, thyroid dis of the skin, he believes that hot food and turbances, etc. drink should be suspected in the etiology The possible partplayedby hereditary factors is hard to investigate because ofstomachcancer. Wynder'4 believes there is evidence many peopledeveloping cancerof the which would link Plummer-Vinson's dis stomachdo notknow thecauseof death
that injury to the stomach may be pro duced. On the basis of this finding and
156
of their parents or grandparents. How ever, as time goes on it will be possible to study this question more accurately be cause of the increased numbers of bi opsies. surgical pathological examinations, and necropsies. It is believed that some areas of Japan have especially high incidence rates for stomach cancer. It has been stated that there is much close marriage in the high incidence areas. If this is true, there may be hereditary factors in stomach cancer which are passed on by the genes and made more prevalent by close marriage.
Stressand Emotional Factors The possibility that stress and emo tional factors may play a part in the eti ology of gastric cancer is worth consider ing. Oriental people, especially Japanese, are usually considered very stoical. This has been part of their culture and teach ing for many years. They are the type who seldom complain and have good self control. Along with this, they usually work hard and are very conscientious. Strode― has shown that the incidence of benign ulcers in Japanese men is one and one half times higher than it is among Cau casian men in Hawaii. Segi' states: “¿MostJapanese scholars believe that stomach cancer often has an etiologically close association with stom ach ulcer. Researchers in other countries usually do not agree with this opinion.― He has shown a high positive correlation between the incidence of ulcer of the stomach and that of gastric cancer and has reported that the death rate from stomach cancer tends to be high in gen eral in a country with a high death rate from stomach ulcer. He has confirmed this statement statistically. It is quite well accepted that emotional factors may play a part in the production of benign ulcers of the stomach. Ivy' sus pects worry in the etiology of gastric can cer. It seems logical to consider that forces or factors which can produce benign con ditions such as ulcers can. under suitable circumstances, produce malignant changes. The suitable circumstances may possibly
be brought about by dietary and nutri tional factors as well as oral health and
occupational exposures alongwithheredi tary influences. The cancer ceded by gastritis.
may be pre
Oral Health It older oral have
is believed by some workers that Japanese men in Hawaii have poor health. No definite statistical data been assembled on this matter as yet.
It willbe necessary to studythisvery carefully to determine whether infection in the mouth, poor mastication, or other factors brought about by poor oral hy giene have any influence on production of gastric cancer. Occupational
Factors
An attempt should be made in an epi demiological study of gastric cancer to determine whether chemicals which could be irritating to the stomach might enter the body either through the nose or mouth and eventually reach the stomach. No spe cific chemicals have been suspected thus far. However, if certain substances seem implicated after preliminary investigations they should be studied specifically. A high percentage of Japanese men in Hawaii are in occupations where they are
exposedto insecticides, weed killers, ro denticides, etc. Itmay be possible toarrive at some conclusion regarding the probabil ity of these substances playing a part in the etiology of gastric cancer after studies have been conducted. Epidemiologic
Speculation
Although the epidemiology of gastric cancer is not clearly defined some perti nent factors have been discussed. The epidemiology of gastric cancer is probably quite complex. The data at hand seem to indicate that gastritis and gastric polyps are precancerous conditions. Per haps a vitamin B1 and protein deficiency along with poor oral health. chemicals taken into the stomach through the mouth. hot food and drink, emotional influences.
157
and a background of hereditary predis position may cause gastritis and the neo plastic changes found in stomach cancer. If it can be shown that these factors are more prevalent in Japanese men than in
other men we may have not only clues re garding the high incidence of this disease in Japanese men but also basic informa tion on the epidemiology of gastric can cer in all people.
References 1. Aird, 1., and Bentall, H. H.: A relationship between cancer of stomach: and the ABO blood
groups. Brit. M. J. 1:799, 1953. 2. Ivy, A. C.: Experimental observations on thee etiology 0/ gastric carcinoma. 1. A theoretical analy sis of the problem. I!. The effect of heat, browned overheated fats, food dyes and carcinogenic hydro carbons on the gastric mucosa. Gastroenterology
28:325-359, 1955. 3. Larsen, N. P.: Cancer, 1930, unpublished data, (A vailable at Honolulu County Medical Library.) 4. McClanahan, B. I.; Mitchel, 1. A., and Mi/li ken, H. E.: Carcino,na of the stomach in Hawaii; a review
of 121 gastric
lesions
at the Queen's
Hos
pital. Hawaii M. J. 8:32-33, 1948. 5. McLester, J. S., and Darby, and Diet in Health and Disease,
W. J.: Nutrition 6th ed. Philadel
phia. W. B. Saunders. 1952; pp. 70-72. 6. Quisenberry, W. B.: The epidemiologic ap proach to the problem of gastric cancer. Proceed ings
of
the
Philadelphia.
Third
National
I. B. Lippincott
Cancer
Conference.
Co. 1957; pp. 721-729.
7. Quisenberry, W. B.; Tilden, 1. L., and Rosen gard, J. L.: Racial incidence of cancer in Hawaii;
a study
of
3,257 cases of
malignant
disease. Hawaii M. J. 13:449-451, 8. Rhea, T. R.: A comparative
neoplastic
1954. study of the mnor
tality
from,: gastric
cancer
in Hawaii.
Hawaii
M.
J.
12:107-112, 1953. 9. Segi, M.: Obsersateom: at, tile Mortality from Ulcer of Stomach and Duodenum on the basis of the Vital Statistics Data. (A part of the report pre sented to tile International Society of Geographical Pathology by Dr. T. Kurokawa and Dr. A. Okabayashi.) Mimeographed report dated January,
1957. 10. Segi, M.; Fukushimna, 1.; Fu/isaku, S.; Kuri hara, M.; Saito, S.; Asano, K., and Nagaike, H.: Cancer
‘¿norbidit;'in Miyagi
Prefecture,
Japan,
and
a comparison with snorbidity in the United States. J. Nat. Cancer Inst. 18:373-383, 1957. 11. Steiner, P. E.: Cancer: Race and Geography. Baltimore. The Williasns & Wilkins Co. 1954; pp. 67-68. 12. Strode, J. F.: Personal comnmunication. 13. Strode, J. E.: Observations on cancer of ti:e stomach in Hawaii; a study of 140 consecutive cases coming to surgery. Hawaii M. 1. 10:173-177, 1951. 14. Strode, I. E.: Giant hypertrophy of gastric mucosa (hypertrophic gastritis). Surgery 41:236-247, ‘¿957.
15. Wynder, F. L.: Ion-occupational aspects 0/ environmental cancer. CA-Bull. Cancer Progr. 7:1420, 1957.
References to Neoplasms of the Stomach in Previous Issues of CA 1:112, 1:120,
May, May,
1:123, 2:122, 2:123, 2:128, 2: 131,
May,
1951—The changing prognosis for cancer of the stomach. 1951—Diagnosis of gastrointestinal cancer in the office of the general practitioner. l9Sl—―New stomach― from colon segment.
July,1952—Somemilestones in therecognition of gastric cancer. July,I952—Present cureratesforcancerof thestomach. July,
I 952—Notes on gastric cancer and gastric ulcer. July,1952—An improvement of 180 per cent in the five-year--survival
rate
ofpatients withcancerofthestomach. 2:135, July, 3:57, March, 3:180, Sept., 3:184, 4:99, 4:133, 6:129, 6:136, 7:21,
158
1952—Cancer clinic. 1953—Early detection of carcinoma of the stomach. 1953—Changes in surgery for carcinoma of the stomach 1940 through 1952. Sept., 1953—Office experience with the cytological technique. May, I 954—Cancer of the stomach need not be feared. July, 1954—Cytology and gastric-cancer diagnosis. July. 1956—Gastric cytology. July, I 956—Cancer clinic. aspects in the etiology of occupational cancer. Jan.,1957—Environmental
