CANCER RESEARCH 35, 3240-3245,November 1975

Summary

The population of California and the San Francisco BayArea has a number of ethnic components that differ in thefrequency with which certain cancers occur. Mortality ratesfor California Japanese and incidence data from the cancerreporting system of the Bay Area are analyzed for thecancer sites considered related to nutrition. The AmericanJapanese of California are particularly amenable to epidemiological study because of the cancer data available fromJapan for comparison with that of the California Japanese.The cancer rates occurring among the successive generations of the Japanese in California are compared to the ratesin Japan and the white rates for the Bay Area. Gastriccancer rates undergo a stepwise reduction from the highrates in Japan to the intermediate rates of immigrantJapanese and the lower rates for the American born. Coloncancer rates are increased about equally in both generationsofJapanese and are approaching the white rates. Cancers ofthe breast, uterine corpus, and ovary in women and theprostate for men are rapidly approaching the rates for thewhite population. Etiologies are continually being identifiedor indicated for a number of these cancers by epidemiological studies, and more specific identification of carcinogenicmechanisms should be possible by other disciplines.

The purpose of this conference is to consider the role ofnutrition in the causation of cancer. This is a subject ofobvious importance. However, to paraphrase Mark Twain'scomment concerning the weather, as epidemiologists we liketo talk about the relationship between nutrition and cancerbut no one does much about it. Ifwe accept the premise thatmuch of cancer can be ascribed to our environment, we haveto recognize that we encounter our environment largelythrough our skin, our respiratory tract, and our alimentarytract. I presume we shun the last-named environmentalexposure route because of the complexity it presents.Defining adverse environmental exposures for the skin andrespiratory tract presents no great problem, but this is nottrue for the alimentary tract. The food and water weconsume provide vehicles for a wide range of non-nutrientchemicals used in the processing and preserving of nutrients,as a route for the many drugs taken for medicinal and other

â€P̃resented at the Conference on Nutrition in the Causation of Cancer,

May 19 to 22, 1975, Key Biscayne, Fla. Supported in part from ContractNO I CP 33353,National Cancer Institute.

reasons, and the inadvertent contaminations that may occurin food production and handling. In addition to thevehicular role of alimentation, there is presumptive evidencethat the normal constitutents of diet may play a carcinogenic role through metabolites or indirectly through influencing the endocrine milieu. Given the carcinogenicpotentialities of both normal and abnormal constituents ofnutrition, the difficulty in conversion of food constituents toqualitative and quantitative measurements and the need tohave historical information for the time when carcinogenesis is presumed to have been initiated should explain thereluctance of epidemiologists to invade this field of work.

“Natural experiments― have developed in which dietarychanges have occurred among populations of people withconcomitant changes in cancer occurrence for specific tissuesites. These experiments have served to select betweencompeting genetic and environmental hypotheses as explanations of regional population differences. The UnitedStates has been the setting for many of these experiments,and we are all familiar with the leading role of Bill Haenszelof the National Cancer Institute in determining the cancer

experience ofthe many migrant populations as they becomefused into the United States culture and way of life.

California provides points of entry for a large portion ofthe Asiatic migrant populations. It has also attractedsizeable Mexican American and southern black populationsseeking improved economic opportunities that are lackingin the areas of their birth.

In Table 1, incidence rates for all sites and for certainsites of cancer for the 5 countries of the San Francisco BayArea (Table 1, Footnote b) are presented. The sites werechosen for their possible relationship to digestion andnutrition. It may come as a surprise to see that black malesexceed all population groups for total cancer. Censusunderenumeration may be responsible for some of theexcess of total cancer, but the excesses of specific cancersites can be shown to be real by examinng the sitedistribution in age-specific groups. The excesses of blackmales are most pronounced for esophagus, stomach, andpancreas as digestive organs. The excess for prostate is alsopronounced and included here as an endocrine-dependentorgan. The white population otherwise leads all populationsin total cancer occurrence. For the oriental populations, theChinese exceed the Japanese for total cancer.

For specific cancer sites, the nasophar.ynx is included toshow that it persists as a remarkable excess for Chinese thathas so far defied explanation and has been under study byDr. Brian Henderson ofthe University ofSouthern Califor

CANCER RESEARCH VOL.353240

Cancer Epidemiology in Populations of the United States—with.Emphasis on Hawaii and California--and Japan'

John E. Dunn, Jr.

Bureau of Adult Health and Chronic Diseases, Department of Public Health, Berkeley, California 94704

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SiteMaleWhite FemaleMaleBlack FemaleCh MaleineseFemaleJapaMaleneseFemaleAll

cancer336.1306.4390.4258.4292.8231.6157.5187.2Nasopharynx0.80.41.2O.4c21.87.41.0'0.0Esophagus4.52.217.04.110.82.2c2.8c2.2cStomach13.66.925.67.714.012.019.823.7Colon32.727.328.123.827.515.916.022.5Rectum

andanusI1.710.512.49.022.310.819.98.3Liver3.21.55.01.623.55.50.0l.6cPancreas11.17.117.510.310.65.96.8c7.lcBreast0.888.71.564.50.449.10.044.1Corpus33.615.117.915.9Ovary15.110.27.36.0Prostate51.689.920.520.7

WhiteNegroMalesFemalesMalesFemalesAreacColondColon

andrectumColonColon

andrectumColonColon

andrectumColonColon

andrectumNorth

SouthWest34.5

28.537.352.7

41.355.430.8

26.030.842.4

34.742.334.5

23.521.253.3

30.834.730.5

22.720.543.2

30.327.8

Cancer Epidemiology

Table I

A verage annual age-adjusted cancer incidence ratesafor selected sites in the San Francisco-Oakland standardmetroplitan statistical area―for the years 1969-1973

a Rates! 100,000.b Counties included: San Francisco, San Mateo. Mann, Alameda, and Contra Costa.

C Based on 5 cases or less.

nia and the late Phil Buell of our staff. Esophageal cancer isexcessive among Chinese males along with black males, asmentioned earlier. Gastric cancer, which leads all othercancer sites among men in Japan and has the usualmale:female sex ratio of nearly 2: 1 (4), does not differentiatebetween the sexes in our incidence data. This had previouslybeen found for the American-born Japanese (Nisei) fromstatewide mortality data, which reflected a reduction in themale rates without a similar change in the female rates (2).The surprising finding is that black males have the highestgastric cancer rate, exceeding the Japanese male rate in theSan Francisco Bay Area. This excess seems to be peculiar tothe black male, since the rate for black women is about thesame as for white women and less than that for eitherJapanese or Chinese women.

Before considering cancer of the large bowel, attentionshould be drawn to the large excess of liver cancer amongChinese males. This excess, to a lesser extent, also appliesto Chinese women as compared to other women of the BayArea. These excesses are limited to hepatocellular cancersand do not extend to those of the gallbladder and bile ducts.

Cancer of the pancreas, as pointed out before, is another sitefor which there is a considerable excess among black males,which seems to be true as well for black women whencompared to other women.

One of the cancer sites most responsive to new environmental surroundings experienced by migrant populations iscancer of the colon. In Japan the rate for colon cancer isroughly one-tenth of that for stomach cancer. The SanFrancisco Bay Area incidence data indicate the rates forthese 2 sites among Japanese are nearly the same, and thefemale colon cancer rate exceeds that for men. ThisJapanese female excess had been found earlier in Californiamortality data (5).

In Table 2, incidence rates for colon and colon plusrectum from the Third National Cancer Survey for 1969 areshown for blacks and whites by region of the United States.Both blacks and whites of the south have lower rates thanfor the other regions. The western cities have attractedlarge segments of their growing populations from themiddle-western and eastern parts of the United States. Thecolon cancer rates for the white population most closely

Table 2

Age-adjusted incidence rates―for colon cancer and colon cancer plus rectum from the Third NationalCancerSurveybfor the north, south, and westregionsby raceand sex, 1969

a Rates/l00,000 and adjusted to 1970 United States population.b Preliminary Report, Third National Cancer Survey, 1969 Incidence, Biometry Branch, National Cancer

Institute.C North, Detroit, Iowa, Minneapolis-St. Paul, Pittsburgh; South, Atlanta, Birmingham, Dallas-Ft. Worth;

West, Denver,San Francisco-Oakland.d Colon excludes rectosigmoid; rectum includes rectosigmoid.

NOVEMBER 1975 3241

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J. E. Dunn, Jr.

matches that for northern whites. For the blacks, the coloncancer rates are more comparable to those of the southernblacks. The data for northern blacks are nearly identical tothose of northern whites. Since three-fourths of blacks in theSan Francisco Bay area were born in the south, it isexpected that their colon cancer rates will increase with timeto reach the white rates, as has already happened in thenorthern areas. The Kaiser Foundation Research Institutehas a case-control study underway to determine dietarydifferences between black colon cancer patients and controlsin the Bay Area. A collaborative study is being carried on atthe same time in Atlanta.

Of the Asiatic populations of California, the 1 that ismost amenable to epidemiological study is the Japanese.This is largely because there are reasonably good data forthe Japanese in Japan for comparison with the immigrantJapanese American population and their progeny, alongwith other components ofthe United States population. Thewell-known contrasts between the Japanese of Japan andthe American white population are: high gastric cancer ratesin Japan; low colon cancer rates in Japan; low rates forcancers of the breast, uterine corpus, and ovary amongJapanese women; and low prostatic cancer rates amongJapanese men. These are the cancer sites most likely to berelateddirectlyor indirectlyto nutrition.

The gastric cancer rates exceed by far those of any othersite for both sexes in Japan. Intuitively, one would feel thismust be related to carcinogenic action of something ingested, since the stomach is the organ of initial andprolonged exposure to the environmental components ofnutrition. The possibility of achlorhydria as a precursor ofcancer was not supported from general population findingsamong Japanese of California (6). Pernicious anemia as aprecursor disease and the higher frequency of blood group Aamong Japanese and its association with gastric cancercannot explain more than a small fraction of the high gastriccancer rate among the Japanese of Japan. The recentpublication by Haenszel et al. (9), based on a dietary studyof Japanese in Hawaii and in Japan, quite convincinglyincriminates pickled vegetables and dried, salted fish as theimportant constituents of the traditional Japanese dietrelated to the occurrence ofgastric cancer. This is supportedby observations of gastric mucosal damage from pickledvegetables(10).

Colon and gastric cancer incidence rates often havereciprocal relationships in various populations. This is truefor the Japanese in Japan, and among American Japanesethe reduction in gastric cancer rates is accompanied by arise in colon cancer rates. Haenszel et al. (7) have recentlypublished a companion study to the gastric cancer studyindicating that colon cancer in Hawaiian Japanese is relatedto the consumption of meat and legumes, with beef andstring beans being the leading representatives of these fooditems.

The very low breast cancer rate for Japanese women inJapan has always been of interest as possibly harboring ananswer to the question of why this is the most frequentcancer of women in the United States. The work ofMacMahon et al. (11), demonstrating the differences inthe estrogen profiles of Japanese and American women,

particularly in younger women, and the recent report of theshifting of the profile toward that of Caucasian women inHawaiian Oriental women (3), suggests the possible role ofdietary change mediated through hormonal changes.

Prostatic cancer as a clinical disease occurs very infrequently among Japanese men in Japan as compared to menin the United States. However, the finding of latent diseasein the histopathological examination of prostatic glands ofJapanese men in Japan and men in the United States do notdiffer markedly. A histopathological study of prostaticglands of Japanese men of Hawaii and Japan foundproliferative activity of latent cancers more frequent inHawaii (1). This is compatible with the increase in mortalityfrom prostatic cancer found in American Japanese ascompared to those in Japan (2, 8).

In the light of what has been presented, the cancerexperience ofCalifornia Japanese will now be considered. InChart I, the population ofJapanese in California at the timeof the 1970 census is presented by age, sex, and place ofbirth. The distribution by place of birth is based on a 1%sample of the population. At this time 77% of the Japaneseare American born and 23% are foreign born. The male andfemale American born are about equal numerically, and allbut 3 to 4% are still under age 60. On the other hand, theforeign-born segment (Issei) of the Japanese population istwo-thirds female and one-third male. The excess of femalesis almost completely accounted for by those ranging in agefrom their 20's to their 50's, with the largest proportion inthe 35- to 44-year age bracket. These women are predominantly identified with marriages to American men servingassignments in Japan and elsewhere. In the present contextthey would be quite different from Issei immigrants of thepast as to degree and rate of acculturation.

Aside from the excess of Issei females just discussed, thenumbers of Issei males and females are comparable over theyounger and older ages. The California Japanese populationover age 60 is composed of two-thirds Issei in both sexes.

Mortality Rates

The age-specific gastric cancer mortality rates for California Japanese for the period 1968 through 1972 are shown

40,000

Chart I. California Japanese by age, sex, and nativity in 1970.

U.S. Born— Male

——@@ Female

Foreign-born______Male

———— Female

30 ,000

20,000

10,000

00 8010 20 30 40 50 60 70

A@e

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U.S. Born_____ Male

@@——Female

Foreign-born—Male———— Female

Okayama, Japan—.—— Male

—..----- Female

Cancer Epidemiology

in Chart 2. The rates for Japanese males and females inOkayama Prefectureofiapanfortheyears1963to1967arealso presented for comparison. It is readily apparent thatthe gastric cancer mortality rates have undergone a stepwisereduction, 1st in the Issei or immigrant population and a2nd further reduction in their progeny. The male and femalecomponents of the latter have quite comparable ratesthrough age 60. The small proportion of the American-bornJapanese population beyond age 60 makes the rates forolder ages very unstable. The age-adjusted gastric cancerincidence rates among the San Francisco Bay Area Japanese males and females show no significant differences, indicating that there has been a greater reduction in malerates than in females (Table 1). Ifthis were true, then Chart2 suggeststhat this has taken place primarily in the American-born population. This question will be considered further with incidence data.

In Chart 3, the age-specific mortality rates for cancer ofthe colon by sex and nativity are shown for the CaliforniaJapanese population. Cancer of this site occurs at a lowfrequency in Japan. From Chart 3 it is apparent that thestepwise reductions seen for gastric cancer in successivegenerations are not repeated by stepwise generation increases for colon cancer. In fact, the rates are higher for theimmigrant than for the American-born Japanese, althoughthis is more likely attributable to the small numbers,particularly for the Nisei population over age 60. In anycase, no conditioning protective effect is evident for theearlier years of life spent in Japan in connection with coloncancer, such as the opposite susceptibility effect that seemsto be the case with cancer of the stomach.

Incidence Data

In Table I , age-adjusted incidence rates were given for theJapanese males and females of the San Francisco Bay Areain comparison with other ethnic groups for cancer sitesconsidered to have some relationship to nutrition in itsbroadest sense. Unfortunately, the Japan incidence datacannot be examined by nativity because we do not have thisinformation routinely available for cases. However, fromthe nativity data for the Japanese population of California,we know that the population under age 60 is predominantlyAmerican born, whereas over age 60 the Japanese population is two-thirds foreign born. The incidence cases developing during the 5 years from 1969 to 1973 will be examinedfirst in comparison to the expected cases if the Japanesepopulation of the Bay Area were experiencing the agespecific cancer rates of the white population of this area,and also with the rates for the Prefecture of Okayama,Japan.In Table 3, the observednumber of casesof various

cancer sites occurring among Japanese males and females ofthe San Francisco Bay Area are compared to the expectednumbers of cases if the rates for the white population of thearea and those for Okayama were experienced. Gastriccancer cases for males were only one-fourth as frequent asOkayama rates would predict and only two-thirds greaterthan would be expected using white rates. Japanese females

I

500

400

300

200

<25 35 45 55 65 75+Age

Chart 2. Cancerof the stomachmortality rates/ 100,000for CaliforniaJapanese in 1968 to 1972 and for Okayama, Japan, in 1963 to 1967 by ageand sex, and by nativity for California Japanese.

200

Age

Chart 3. Mortality rates for cancer of the colon per 100,000 forCalifornia Japanese by sex and nativity.

had 3 times as many gastric cancers as would be expectedwith white rates and 40% of the number expected fromOkayama rates. These findings are consistent with theprevious observation that male Japanese gastric cancerrates are reduced to a greater extent than are the rates forfemales among American Japanese, when compared toJapanese rates in Japan. In Table I, it was seen that theusual sex difference in that rate for this site has disappearedin the Bay Area Japanese population.

For colon cancer both males and females have 3 to 4times the number of cases that Okayama rates wouldpredict. Females have 80% of the number of cases thatwould make them comparable to white females and Japanese males a little over one-half of that for white males.Cancers of the rectum and anus are about twice the numberOkayama rates would provide, and there appears to be nodeficiency as compared to whites.

Among women, more than 3 times the number of cancersof the breast occurred than would have been expected with

Okayama rates and 57% of the cases that would have

U.S. Boi@z@—Male@—@Fenia1e ,1'

/1'Foreign -born—Male /1— ——— Female

-I

@ I

150

100

50

<25 35 45 55 65 75+

3243NOVEMBER 1975

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Cancer siteJapaneseobservedcasesExpected

cases;Okayamab

age-specific ratesExpected

cases;San Francisco-Oakland SMSA white

age-specificratescMalesStomach1563.39.0ColonI

I3.220.3Rectumandanus135.310.8Prostate163.033.1FemalesStomach1845.06.2Colon194.623.4Rectum

andanus74.89.7Breast4713.582.1Uterinecorpus132.226.1Ovary61.813.2

CancersiteAges<60Ages6O+ObservedExpectedbObservedExpectedbMalesStomach32.3126.7Colon45.2715.1Rectum

andanus43.297.6Prostate22.71430.4Stomach4Females

1.8144.4Colon66.81316.5Rectum

andanus33.349.7Breast4155.7626.4CorpusuteriII15.6210.4Ovary59.4I3.8

J. E. Dunn, Jr.

resulted from rates for white women. Similarly, for cancersof the ovary and uterine corpus there are about one-half ofthe cases that would result from rates for white women, and6 times the number of ovarian cancers and 3.5 times thenumber of uterine corpus cancers predicted from Okayamarates. Similarly, for prostatic cancer in males there areone-half of the cases that would be expected from whiterates but over 5 times the cases that Okayama rates predict.

In Table 4, the observed cases of the various cancer sitesin Table 3 are divided between those occurring amongJapanese men and women of the Bay Area before age 60and for those that age and older. The expected cases usingrates for the white population of the area are presented forcomparison. Again, it should be pointed out that the

Japanese younger than 60 years are predominantly Amencan born, while those 60 and older are largely Issei.

For males under age 60, the gastric cancers observed areone-third more than expected, while olden males had almosttwice the number expected from white rates. Females underage 60 had twice as many gastric cancers as rates for whitewomen would predict and over 3 times the number amongthose 60 years and older. Again, Japanese male rates areproportionately nearer to white male rates than Japanesewomen are to the rates for white women.

The observed cases of colon cancer for Japanese underage 60 are very close to the expected number from whiterates for both men and women. For those 60 years and olden,this is close to being true for females, but males have

Table 3Observedcancercasesof indicatedsitesamongJapaneseof the San Francisco-OaklandSMSA ,a /%9 /973,

comparedto expectedcasesusingage-specificratesof Okayama,Japan and whitepopulation of the SanFrancisco-Oakland SMSA

a SMSA, standard metropolitan statistical area.

b Ref. 4, pp. 208, 209.

C San Francisco Bay Area Resource for Cancer Epidemiology.

Table 4Observedand expectedcancersof certain sitesamongJapaneseof the San Francisco-Oakland

SMSA,' J%9_J973

a SMSA, standard metropolitan statistical area.b Expected number computed using age-specific white rates for San Francisco-Oakland SMSA

1969-73.

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Cancer Epidemiology

one-half of the expected number. Cancers of the rectum andanus are not deficient for Japanese people compared towhite, with the possible exception of older women.

Women under age 60 had three-fourths of the expectednumber of breast cancers that white rates would predict,71% of the cancersof the uterine corpus, and a little overone-half of the ovarian cancers. For those 60 years andolder, these proportions are 23, 19, and 26%, respectively.This indicates that the American-born Japanese are approaching the white population in the frequency of occurrence of cancer in these sex organs. Similarly, for prostaticcancer among men, Japanese men under age 60 have nearlythree-fourths of the expected cases from white rates andalmost one-half of the number expected for men 60 yearsand older.

Conclusions

The Japanese are a particularly interesting population tostudy for cancer occurrence because of the strikinglydifferent diet in Japan as compared to the United States.The comparability of the available data in Japan with thosein the United States and the opportunity this provides forcomparing the Japanese in their homeland with thosemigrants who have adopted the United States as their newhomeland show some remarkable results. The shifting ofemphasis of gastrointestinal cancer from stomach to colonand the remarkable increases in breast, uterine corpus, andovarian cancer in women and prostatic cancer in men fromthe low rates in Japan toward those indigenous in the UnitedStates has to have explanations waiting for elucidation.Progress has been made in the epidemiological studiesreferred to, and now is should be possible to identify morespecifically the chemical, biological, and endocrinological

mechanisms that may be involved in the carcinogenicprocess.

References

1. Akazaki, K., andStemmermann,G. H. Comparative Study of LatentCarcinoma of the Prostate among Japanese in Japan and Hawaii. J.Nail. Cancer Inst., 50: 1137—1144,1973.

2. Buell, P., and Dunn, J. E. Cancer Mortality among Japanese lssei andNisei of California. Cancer, 18: 656-664, 1965.

3. Dickinson, L. E., MacMahon, B., Cole, P., and Brown, J. B. EstrogenProfiles of Oriental and Caucasian Women in Hawaii. New EngI. J.Med.,291: 1211-1213,1974.

4. Doll, R., Muir, C., and Waterhouse, J. (eds), Cancer Incidence in FiveContinents, Volume 2, International Union Against Cancer, NewYork: Springer-Verlag, 1970.

5. Dunn, J. E., and Buell, P. Gastro-intestinal Cancer among the EthnicGroups in California. The Proceedings ofthe Third World Congress ofGastro-enterology, VoL 1, pp. 35-42, 1967.

6. Grinspoon, L., and Dunn, J. E. A Study of the Frequency ofAchlorhydria among Japanese in Los Angeles, N. NatI. Cancer Inst.,22:617-631,1959.

7. Haenszel, W.@Berg, J. W., Segi, M., Kurihara, M.. and Locke, F. B.Large Bowel Cancer in Hawaiian Japanese. J. NatI. Cancer Inst., 5/:1765-1779,1973.

8. Haenszel, W., and Kurikara, M. Studies of Japanese Migrants.I. Mortality from Cancerand Other DiseasesamongJapanesein theUnited States. J. NatI. Cancer Inst., 51: 1765-1779, 1973.

9. Haenszel, W., Kurihara, M., Segi, M., and Lee, K. C. StomachCanceramongJapanesein Hawaii. J. NatI. CancerInst., 49:969-988,1972.

10. MacDonald, W. C., Anderson, F. H., and Hashimoto, S. HistologicalEffect of Certain Pickles on the Human Gastric Mucosa. A Preliminary Report. Can. Med. Assoc. J., 96: 1521-1525, 1967.

11. MacMahon, B.,Cole, P., Brown,J. B.. Oaki, K., Lin,T. M., Morgan,R. W., and Woo, N-C. Oestrogen Profiles of Asian and NorthAmerican Women. Lancet, 2: 900-902, 1971.

3245NOVEMBER 1975

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1975;35:3240-3245. Cancer Res   John E. Dunn, Jr. 

and Japan−−Emphasis on Hawaii and Californiawith−−Cancer Epidemiology in Populations of the United States

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