- Email: [email protected]
Epidemiology of breast cancer with special reference to the role of diet
PREVENTIVE
MEDICINE
7, 173- 195 (1978)
Epidemiology
of Breast Cancer with Special Reference to the Role of Diet1 TAKESHI
Epidemiology
Division,
National
HIRAYAMA
Cancer Center Research Chuo-ku, Tokyo, Japan
Institute,
Tsukiji 5-Chome,
Breast cancer is still relatively infrequent in Japan. However, both mortality and morbidity rates have sharply increased in recent years, especially in ages 45-59. The risk was noted to be 8.5 times higher in women of high socioeconomic strata eating meat daily compared with women of low socioeconomic strata who do not eat meat daily, when 142,857women aged 40 years were followed for 10 years. A high positive correlation was found between per capita fat intake and adjusted death rates of breast cancer in different districts of Japan. It was estimated that the breast cancer death rate will rise to the U.S. level when Japanese dietary fat intake approaches present day U.S. levels. The close correlation with fat intake was noted to come mainly from the consumption of pork and animal fat. The ratio of recent increase in breast cancer death rates was also found to be under the combined influence of animal fat and AF2, a highly mutagenic food additive widely used in Japan from 1965to 1975 and shown to produce mammary carcinoma in rats. A series of case-control studies reveals the higher risk of breast cancer with the increase in body size especially in postmenopausal women. The recent breast cancer increase could therefore be a reflection of the fact that women in Japan are becoming heavier, especially after age 30.
INTRODUCTION In order to explain the exceedingly low incidence of breast cancer in Japan, many epidemiological studies were conducted in the past with regard to incidence in migrants (l), reproductive histories (6, 8, 10, 1l), diet (5), and body size (2-4). Both patterns of breast cancer occurrence and background situations are, however, rapidly changing in Japan. The purpose of this paper is to discuss the possible reasons for such lower incidence and also for the recent increase of breast cancer in Japan, with special reference to the role of dietary fat intake and body size based on a series of epidemiological studies conducted in recent years in Japan. MATERIALS Vital statistics in Japan from 1955 to 1975 and results of the National Nutritional Survey from 1949 to 1973 provided the data for this presentation. A population prospective study on the health consequences of selected risk factors has been in progress in Japan since the fall of 1965 (9). In total, 142,857females, aged 40 years and over, in 29 Health Center Districts in Japan, interviewed from October 1 to December 31, 1%5, have been followed by establishing a record linkage system between the risk factor records, a current residence list obtained by specially planned annual census, and death certificates. The 10 year follow-up results of this ’ Presented at the Breast Cancer, Diet and Epidemiology Meeting, sponsored by the U.S.-Japan Cooperative Cancer Research Program, NCI-JSPS. Seattle, Washington. March 14- 15, 1977. 173 0091-7435/78/0072-0173$02.00/O Copyright 411 right\
c 197X hy Academic Pres\. Inc of reproductmn xn any form rewrved
174
TAKESHI
HIRAYAMA
study were used as the material. Out of 1,330,382 person-years of observation, 142 women died of breast cancer. The SMR for these women was calculated by various risk factors. RESULTS A. Descriptive Epidemiology Breast cancer is known to be infrequent in Japan. Out of 80 cancer registries in the world, Okayama, Miyagi, and Osaka ranked 74th, 7&h, and 79th, respectively, in the list arranged according to the magnitude of breast cancer incidence rate (Fig. 1). Both mortality (Table 1, Fig. 2) and morbidity rates (Fig. 3) for breast cancer are, however, sharply increasing. The number of annual breast cancer deaths doubled during the past 20 years in Japan: 1572 in 1955 and 3262 in 1975 (Table 2, Fig. 4). The death rate has also steadily increased in recent years: 3.5 and 5.8 per 100,000 in 1955 and 1975, respectively. The extent of increase by age groups is shown in Fig. 5. Breast cancer death rates, especially at postmenopausal age, are higher in large cities (Figs. 6 and 7). The ratio of increase is also highest in large cities (Fig. 8). Breast cancer is known to be quite frequent in the higher socioeconomic strata. SMRs for breast cancer in the current prospective study were 23.6 for the highest strata (professional, managers), 13.7 for the middle strata (clerks, sales, service, transportation, and factory workers), and 8.9 for the lowest strata (agriculture, fishery, miners). B. Analytic Epidemiology 1. Reproductive history. As shown in Fig. 9, the age-specific mortality rate for single women in Japan is quite close to the rate for U.S. white women, while that for married women is far lower than U.S. figures. A series of retrospective studies and the on-going prospective study also clearly showed a strikingly higher mortality rate for breast cancer in single women. It appeared that if women marry, even if they are nonparous, the risk of developing breast cancer goes down. The risk further goes down with the increase in number of children, The effect is independent of the effect of age at first marriage (Fig. 10). The striking international variation in breast cancer incidence rate is, however, not explained by the difference in factors related to reproductive history. 2. Dietary fat and meat intake. The promoting influence of diet, particularly dietary fat, was analyzed. The risk-enhancing effect of daily intake of meat was shown by our on-going census population-based prospective study in Japan. A higher standardized mortality ratio of breast cancer was observed in women who ate meat daily, SMR being 1.26 and 2.38, respectively, in age groups 40-54 and 55 and over compared with non- or occasional meat eaters (Table 3). It was 5.90 in women of high socioeconomic status, 1.94 in women of middle socioeconomic status, and 1.10 in women of low socioeconomic status (Table 4). A similar relationship was also observed in another population study in Japan. A higher breast cancer incidence rate was observed in women who eat meat, eggs, butter, and cheese daily in the Adult Health Survey in Hiroshima (Kato) (Table 5). A similar phenomenon was also shown by a correlation study. A high correlation coefficient (Y = 0.842) was observed between dietary fat intake and breast cancer adjusted mortality rates in 12 districts in Japan (Fig. 11). Such a high
U.S.-JAPAN
BREAST
(STANDARDIZED:
CANCER
AND DIET CONFERENCE
175
WORLD POPlJLATION)
FIG. I. Age standardized breast cancer incidence rate [Cancer Incidence in Five Continents, Vol. III, 1976.
40-44 45-49 50-54 55-59 60-64 65-69
40-44 45-49 50-54 55-59 60-64 65-69
Death rate Per 100,000
Ratio to 1955 death rate
Age
100.0 100.0 100.0 100.0 100.0 100.0
6.4 8.7 10.1 11.6 13.6 14.7
1955
103.1 86.2 101.0 103.4 85.3 91.8
6.6 7.5 10.2 12.0 11.6 13.5
‘56
100.0 87.4 96.0 86.2 83.1 72.1
92.2 120.7 113.9 105.2 89.7 85.7
5.9 10.5 11.5 12.2 12.2 12.6
‘58
TREND
6.4 7.6 9.7 10.0 11.3 10.6
‘57
ANNUAL
120.3 93.1 107.9 95.7 84.6 77.6
7.7 8.1 10.9 11.1 11.5 11.4
‘59
100.0 109.2 95.0 95.7 75.7 81.0
6.4 9.5 9.6 11.5 10.3 11.9
‘60
%.9 110.3 113.9 96.6 74.3 88.4
6.2 9.6 11.5 11.2 10.1 13.0
‘61
OF AGE-SPECIFIC
103.1 109.2 103.0 96.6 89.0 83.7
6.6 9.5 10.4 11.7 12.1 12.3
‘62
DEATH
109.4 111.5 102.0 100.9 83.1 76.2
7.0 9.7 10.3 12.1 11.3 11.2
‘63
RATE
TABLE
103.1 111.5 119.8 104.3 69.9 81.0
6.6 9.1 12.1 11.1 9.5 11.9
‘64
106.3 108.0 124.8 108.6 87.5 87.8
6.8 9.4 12.6 12.6 11.9 12.9
‘65
FOR BREAST
1
115.6 113.8 122.8 114.7 94.9 78.9
7.4 9.9 12.4 13.3 12.9 11.6
‘66 6.9 9.9 12.2 12.5 12.9 11.5
‘67
100.0 121.8 122.8 120.7 102.2 87.8
6.4 10.6 12.4 14.0 13.9 12.9
‘68
IN JAPAN,
107.8 113.8 120.8 107.8 94.9 78.2
CANCER
103.1 114.9 120.8 107.8 86.8 79.6
6.6 10.0 12.2 12.5 11.8 11.7
‘69
112.5 121.8 130.7 122.4 102.9 85.0
7.2 10.6 13.2 14.2 14.0 12.5
‘70
1955-1975
118.8 131.0 147.5 127.6 106.6 95.9
7.6 11.4 14.9 14.8 14.5 14.1
‘71
123.4 133.3 147.5 129.3 102.9 91.8
7.9 11.6 14.9 15.0 14.0 13.5
‘72
132.8 132.2 146.5 126.7 114.0 104.1
8.5 11.5 14.8 14.7 15.5 15.3
‘73
121.9 151.7 151.5 141.4 106.6 93.9
7.8 13.2 15.3 16.4 14.5 13.8
‘74
134.4 141.4 168.3 142.2 116.2 98.6
8.6 12.3 17.0 16.5 15.8 14.5
‘75
5
2
$
E
; R g z
U.S.-JAPAN
BREAST CANCER AND DIET CONFERENCE
177
150 140 130 l-20 110 100 90 80 70 a 65-69
‘....‘....‘......d
1955
60
65
70
75 1955 60
-
65
70
751955
60
65
70
75
CALENDARYEARS
FIG. 2. Annual trend of age-specific death rate for breast cancer in Japan, 1955- 1975(1955= 100).
FIG. 3. Trends of age-adjusted cancer incidence rates by selected primary site (Osaka).
178
TAKESHI
HIRAYAMA
TABLE 2 CHANGE
Year 1909 1910 1911 1912 1913 1914 1915 1916 1917 1918 1919 1920 1921 1922 1923 1924 192.5 1926 1927 1928 1929 1930 1931 1932 1933 1934 193.5 1936 1937 1938 1939 1940 1941 1942
IN NUMBER
OF BREAST
CANCER
DEATHS
1909- 1976, JAPAN
Number of deaths 441 437 481 511 504 507 549 537 606 552 535 592 542 570 650 616 647 647 660 708 703 716 752 764 813 855 820 907 943 919 945 934 904 993
(FEMALE)
Number of deaths 1943 1944 1945 1946 1947 1948 1949 1950 1951 1952 1953 1954 1955 1956 1957 1958 1959 1960 1961 1962 1963 1964 1965 1966 1967 1968 1969 1970 1971 1972 1973 1974 1975 1976
969 -
1192 1235 1370 1419 1402 1446 1452 1526 1572 1544 1458 1692 1652 1683 1741 1740 1857 1853 1966 2100 2107 2248 2208 2486 2689 2762 2995 3058 3262 3346
correlation coefficient was not observed with any other nutritional element (Table 6).
The amount of intake of dietary fat in Japan and in the U.S.A. is 52 and 155 in 1973, respectively. It was 23 and 143, respectively, in 1957-1959. Among each nutritional element, dietary fat intake showed the most striking increase in Japan in recent years (Fig. 12). It is of interest to note that the U.S. breast cancer mortality rate was expected
U.S.-JAPAN
BREAST
CANCER
AND
DIET
CONFERENCE
179
3262
3ooc
250C
2ooc
% Y 5 0.
15oc
f 2 a "0
1ooc
z 2 2 5oc
(
I
950
55
I
65
60
1
70
75
YEAR
FIG. 4. Change in number of annual breast cancer deaths, 1950- 1975, Japan.
to be 20 per 100,000 while the actual rate was 18 (adjusted to 1960 population in Japan) by extrapolating the regression line of dietary fat-breast cancer correlation in Japan. Among the food items, the highest correlation was found with the per capita amount of pork intake (Y = 0.895) (Table 7, Fig. 13) and next came the amount of animal fat intake (r = 0.675). The partial correlation study revealed a near disappearance of the above mentioned high correlation between breast cancer mortality rate and dietary fat intake when the effect of correlation with pork intake was taken out. On the other hand, the correlation of breast cancer mortality rate with pork intake still remained high (r = 0.573) even if the influence of dietary fat was removed by calculating partial correlation coefficient (Table 7).
180
TAKESHI
HIRAYAMA
975
974
950-52
937-40
10
20
30 Age
40
50
60
70
80
90
groups
FIG. 5. Age-specific death rate for breast cancer in different years, Japan (female).
150140
150'
l(r5
LUNG CANCER
130 ’
BREAST CANCER
140’ 130
120
120 *
120
110 ’ 100!ETRO- CITIES POCITAN AREAS
COUNTIES
1CKl
CITIES COUNTIES
FIG. 6. Adjusted death rates for cancer of all sites and each site in metropolitan areas, cities, and counties in 1960 and 1970 (ratio to death rate in counties).
U.S. -JAPAN
BREAST
CANCER
AND
DIET
CONFERENCE
181 AREAS
DEATH RATE PER 100,000
FIG.
7. Age specific death rate for breast cancer by urban-rural 160,
difference, 1970, Japan,
LUN6CANCER 156,~
BREAST CANCER 116.7
100
WLITANCITIES CWNTIES AREAS
RETRD- CITIES COUNTIES PDLITAN
FIG. 8. Change in the adjusted death rates for cancer of all sites and each site in metropolitan areas. cities, and counties in Japan (ratio of death rates in 1970 to those in 1960).
MEAT
INTAKE
AND BREAST
Meat
intake 40-54
Daily
Occasional,
CANCER
Obs. person-
years
TABLE 3 RATE, 1966-1975,
DEATH
No. of breast
7 65
27,402 540,265
7 60
rare, none
55+
Daily Occasional, rare, none
Crude death rate
cancer death
51.477 688,590
PROSPECTIVF.
Standardized death rate
1.30
1.26 25.90
25.55
10.89
Il.11 Ratio
JAPAS
il.84 9.43
12.18 9.40
Ratio
STUDY,
2.30
2.38
182
TAKESHI
HIRAYAMA
TABLE 4 SMR
FOR BREAST CANCER BY FREQUENCY OF MEAT SOCIOECONOMIC STATUS, PROSPECTIVE STUDY
INTAKE
AND BY
(1966- 1975)
Frequency of meat intake Socioeconomic status
Occupational category
Daily
Occasional, rare or none
Ratio
High
Professional Managers
85.35
15.46
5.90
Middle
Sales Clerks Service
19.33
9.94
1.94
Low
Factory Transportation Miners Farmers
11.04
10.04
1.10
TABLE 5 BREAST CANCER HIROSHIMA,
INCIDENCE
1965-
RATE BY FREQUENCY OF FOOD TAKEN, 1974, ADULT HEALTH STUDY SAMPLE”
Frequency of food taken Food Meat
Total Case
30
Less than once a week 2
2-4 times a week
Control Em
Case
3992
696
2304
30
13
6
Butter Cheese
Case
316
30
9
Case
3992
2112
30
6
Control Case
872
0.89% (2.10) 1008 9
15 0.67% (0.76)
676
2232
30
18
10
2052
9 1.38% (3.23)
3988
3992
0.90% (2.86) 2568
12
0.88% (1.W Control
23
1104
0.89% (1.00) Ham Sausage
992 0.54% (1.91)
0.43% (1.00) Control
Fish
3982
1.11% (3.83)
0.74% (2.55)
0.32% (1.W Control
11
17 0.29% (1.OO)
Almost daily
0.83% (0.94) 1080 2 0.47% (0.73)
0.66% (0.75) 1512
428
a Breast cancer cases: 1965- 1974; control: adult health study sample examined in 1965-66.
U.S. -JAPAN
BREAST
CANCER
AND
loo I'
,--
DIET
183
CONFERENCE
.’ _--*.--
SINGLE JAPAN(1970)
/I
U.S. WHITES /' (1950-67) ,/'-
10
I
I :4’ ::: I:1’ :Y
MORTALIT RATE PER 100,000
20 25 30 35 40 45 50 55 60 65 70 AGEGROUPS
FIG. 9. Breast cancer age-specific mortality rate by marital status, 1970, Japan.
NUMBER OF 0 CHILDREN
5
IO
I5
20
25
35
30
40
45 4.3
4 SINGLE PURRIED
3 OR NORE AGE AT FIRST
@ARRIAGE
m J
25I
-
24
FIG. 10. SMR for breast cancer by number of children and by age at first marriage, prospective study (1966- 1975, Japan) SMR per 100,000.
184
TAKESHI
HIRAYAMA
TABLE CORRELATION
6 MORTALITY
COEFFICIENT FOR BREAST CANCER ADJUSTED RATE AND NUTRITIONAL INTAKE, 1970, JAPAN
Partial correlation coefficient (1) calorie (2) Animal protein (3) Vegetable protein (4) Fat (5) Carbohydrate (6) Calcium (7) Vitamin A (8) Vitamin B, (9) Vitamin B, (IO) Vitamin C
r =
0.145
0.336
r = 0.361 r = -0.010 r = 0.842 r = -0.412 r = 0.205 r = 0.552 r= 0.449
0.421 0.846
0.851
-0.215 0.850
0.816 -0.215
0.931
0.800
0.921
0.747
0.823
-0.749 0.300 -0.741
r =
0.601
r =
0.317
0.170 -0.028
Significant at 1% level.
This means that in the case of Japanese women, the amount of pork eaten, which is much cheaper than beef, is quite important in raising the incidence of breast cancer (Fig. 14). The national nutritional survey showed a striking increase in per capita intake of pork in Japanese people in recent years (Fig. 15). In Fig. 16, correlation patterns between breast cancer mortality rate and dietary fat, pork intake, and beef intake are summarized. Figure 17 and Table 8 show international correlation between pork intake and breast cancer adjusted mortality rate. 3. Factors responsible for the recent increase. The statistical analysis clearly shows that the ratio of increase in the breast cancer death rate is closely as-
. uwrol
l@wJ KIN0
' KITA KMlW iuimll
I 2.51 35
R’0.W l
WaMJ
ul
45
PERCAPITAWILY FAT his
FIG. 11. Breast cancer mortality
I 5l
1 55
( G)
rate and daily fat intake for 12 blocks inJapan,
1970.
U.S.-JAPAN
BREAST
CANCER
AND
DIET
185
CONFERENCE
FAT 257 25
/
20 ANIML PROTEIN188
15 RATIO TO AJ’tiNT OF INTAKE IN 1955
/.’
.,
TOTALPROTEIN121
lol
0
,*..‘....I.-..fi... 1960
1965 YEARS
1970
FIG. 12. Change in amount of intake of selected nutrients in Japan (1955- 1973) 5.5
. KANT0
.
5.0'
2 z ; t" ggt” 9 !it
2 2
HOKKAIW
4.5-
. 4.0. 4.0.
KINK1
TOHOK” TOHOKU TOKAI I.. ’ . HOKURIKU*
SOUTH
3.5. 3.5.
. KYUSHU .
KINK1
Dz : : 5
5 2 $$
KANT0 II
IItI
’
.. CHUGOKU CHUGOKU
3.0 3.0-
NORTH KYUSHU
r = 0,895
. I 2.5' 2.5-
0
SHIKOKU
10 PORK PER CAPITA DAILY
20
30
INTAKE(G)
FIG. 13. Breast cancer and pork intake, 1970, Japan.
I
186
TAKESHI
HIRAYAMA
TABLE 7 CORRELATION COEFFICIENT FOR BREAST CANCER ADJUSTED MORTALITY AND DIETARY INTAKE (PER CAPITA INTAKE), JAPAN, 1970
RATE
(1) (2) (3) (4) (5) (6) (7) (8) (9) (10) (11) (12) (13) (14) (15) (16) (17) (18)
Breast canceIQ Fat Food of animal origin Food of vegetable origin Cereals Rice Barley Wheat Bread Seeds and nuts Potatoes Sugars Confectionaries Oils and fats Butter Margarine Vegetable oil Animal fat, lard
0.842 0.439 0.380 -0.522 -0.496 -0.207 0.378 0.224 0.174 0.231 -0.505 0.529 0.628 0.626 0.383 0.252 0.675
0.818 0.820 0.805 0.792 0.876 0.813 0.836 0.880 0.847 0.885 0.791 0.811 0.800 0.834 0.907 0.918
0.286 0.200 -0.344 -0.194 -0.482 -0.021 0.129 -0.499 0.280 -0.666 0.269 -0.702 0.498 0.327 -0.646 0.840
(19) (20) (21) (22) (23) (24) (25) (26) (27) (28) (29) (30) (31)
Mayonnaise Beans Fruits Green and yellow vegetables Other vegetables Dried vegetables Salted vegetables Seaweeds Fish and shellfish Fish sausage Meat, poultry. and whale Beef Pork
0.363 0.016 0.060 0.225 0.271 -0.572 0.516 0.053 0.235 -0.212 0.286 -0.487 0.895
0.817 0.857 0.850 0.841 0.882 0.762 0.777 0.843 0.874 0.836 0.827 0.802 0.129
0.054 -0.295 0.236 0.207 -0.531 -0.163 0.020 -0.044 0.484 0.090 -0.011 -0.255 0.573
Chicken Other meats Ham sausage Canned and other meat products (36) Eggs (37) Milk and milk products (38) Milk (39) Cheese (40) Condensed and powdered milk
-0.304 0.031 0.408 0.495 -0.395 0.417 0.361 0.733 0.502
0.842 0.848 0.815 0.842 0.857 0.876 0.816 0.791 0.847
-0.306 0.182 0.189 0.495 -0.477 0.584 0.031 0.635 0.523
(32) (33) (34) (35)
rl.n
a Adjusted mortality rate.
sociated with both daily amount of animal fat intake (r = 0.364) and daily AF2 consumption (r = 0.522) (Table 9). AF2 is a highly mutagenic chemical widely used as a food additive for fish meal, ham, sausages, bean curd, etc. in Japan from 1965 to 1975. The highest correlation was observed when these two factors were combined (r = 0.900) (Table 10, Fig. 18). In view of the high yield of carcinoma of the breast in rats fed an AFZcontaining diet (12), it is most likely that AF2 also
U.S. -JAPAN
BREAST CANCER AND DIET CONFERENCE
5.5
187
. KANT0
I
.
5,o
HOKKAIDO
t
‘KANT0 TOHOKU KINK1
ltt
TOKAI .
I
l . l HOKURIKU
SOiTH KYUSHU KINK1
. NORTH KYUSHU
n’
.
r = 0.942
CHUGOKU
. SHIKOKU I
2.5
4
3.0 EXPECTED
3.5
4.0
RATE POLK AND
4.5
5.0
5.5
LARDINTAKE
Y = 2,662 + 0.0795(+ 2.5gSt FIG. 14. Breast cancer and pork and lard intake, 1970, Japan.
plays a role in promoting breast cancer risk in women in Japan in addition to the influence of dietary fat. 4. Body size. A clear-cut tendency of higher risk with increase in body size was observed in a case-control study carried out on patients in the National Cancer Center Hospital and the Cancer Institute Hospital in 1975- 1976 (1). The comparison of cases and controls revealed a significantly higher risk for breast cancer in heavy (5% or more heavier than national average) women aged 50 and over. (Table 11). Tall women with medium weight also showed higher risk. The effect of
TABLE 8 BREAST CANCER ADJUSTED MORTALITY RATE
AND
BEEF AND Pow
World, 1964- 1965 Japan, 1970 Breast cancer (1) and beef (2) Breast cancer (1) and pork (3) Beef (2) and pork (3) Partial correlation Breast cancer (1) and beef (2) Breast cancer (1) and pork (3) (I Beef less than 54 g per day. b Beef more than 55 g per day.
r,.* = -0.487 r,.3 = +0.895
rp.3 = -0.527 r 12Y13r 23 = -0.042 rl.3y1.2r1.3 = +0.861
28 countries”
12 countries?
+0.708 +0.767 +0.492
+o. 145 +0.213 -0.194
+0..594 +0.684
+o. 194 +0.248
188
TAKESHI
HIRAYAMA
YEARS
FIG. 15. Change in amount of intake of selected food in Japan (1960, 1966-1973) (meat, fats, and oils).
body size on breast cancer risk was similar in large cities, towns, and villages, in women with or without a family history (blood relatives) of breast cancer. The effect of body size is more striking in postmenopausal women, in single and divorced women, and in women with later age at menarche. Compared with thin women, obese women showed a significantly higher risk (Table 12). The relative risk of breast cancer in postmenopausal women by height and weight is shown in Table 13. The risk is 11.5 times higher in tall (over 155 cm) and heavy women (over 65 kg) than in small women. Similar results were obtained by a cross-sectional population study. In Tokushima Prefecture, breast cancer mass screening was carried out for 20,805 women over age 30 (Okazaki). The prevalence rates for breast cancer are noted to be significantly higher in women 160 cm tall or more and weighing 65 kg or more,
U.S. -JAPAN
BREAST
CANCER
AND
DIET
SOCIO-ECMUW
189
CONFERENCE
GEOGRAPHY
r - 0.895
3
ANNUAL TREND
s I
J
FIG. 16. Correlation between pork intake and breast cancer mortality rate, Japan. Breast cancer adjusted mortality rate. Pork per capita daily intake (G).
l
.
IRELAND
l
SWEDEN l
ITALY
l
. CZECHOSLOVAKIA
E z a s
PANAM;\ GREECE
r, ARAB U.R. ,I ISRAEL J, SRI LANKA
POLAND .ROUMANIA l YUGOSLAVIA
BULGbuA
.
J;pAN
PHtLIPPINES l
= = 0.767
.
MEXICO
EL SALVADOR l THAILAND
l
0
.
VENEZVELA 1 CHILE SPAIN,.
lo-
FORMOSA , 10
30
20 PORK PER CAPITA
FIG.
AUSTRIA
NORWAY
.
y
DENMARK
DAILY
INTAKE
40
(G)
17. Breast cancer and pork intake in 28 countries, 1%4- 1965(beef less than 54 g per day)
190
TAKESHI
HIRAYAMA
TABLE 9 DAILY
AMOUNT OF FAT INTAKE (1968), DAILY RATIO OF INCREASE IN BREAST CANCER
Breast cancer adjusted death rate per 100,000
Hokkaido Tohoku Kanto I Kanto II Hokuriku Tokai Kinki I Kinki II Chugoku Shikoku Kita Kyushu Minami Kyushu
AMOUNT OF AF2 CONSUMPTION (1968), MORTALITY RATE (1969- 1974), JAPAN
Ratio of increase 1974
AND
Per capita per day
1969
1974
1969
Total fat 1968
4.08 3.79 3.87 3.75 3.85 3.33 4.06 3.50 2.68 3.13 3.15 3.29
5.74 4.58 5.03 4.94 4.00 4.33 5.12 4.50 4.02 3.25 4.56 3.92
1.41 1.21 1.30 1.32 1.04 1.30 1.26 1.29 1.50 1.04 1.45 1.19
47.1 47.3 58.4 51.9 46.8 46.7 50.3 43.1 50.6 42.7 48.7 46.3
Animal fat 1968
Vegetable fat 1968
AF2 consumption 1968
20.5 16.6 28.9 20.6 18.7 21.7 25.2 19.2 21.7 16.8 20.0 19.6
26.6 30.7 29.5 31.3 28.1 25.0 25.2 23.9 28.9 25.9 28.7 26.7
0.177 0.157 0.120 0.164 0.135 0.157 0.120 0.176 0.186 0.168 0.205 0.148
risk being 17.5 times greater than for women shorter than 149 cm and weighing less than 59 kg (Table 14). C. Operational
Epidemiology
As shown in Fig. 19, a clear-cut tendency towards weight increase is observed in women after age 30 during the past 20 years in Japan. To prevent further increase in breast cancer incidence in Japan, since it does not appear easy to modify factors related to reproductive history, it is of urgent necessity to alert the government, the public, and individuals to the possible danger of excess dietary fat and resulting obesity. It is recommended that dietary goals be established in Japan, as has been done in the U.S. TABLE RATIO
OF INCREASE
IN BREAST FAT INTAKE
CANCER
(1968)
10
MORTALITY RATE (1969-1974) AND DAILY AND AF2 CONSUMPTION (1%8), JAPAN
Total fat
AMOUNT
Animal fat
OF
Vegetable fat
Simple correlation coefticient Breast ca. increasing ratio: fat intake Breast ca. increasing ratio: AF2 consumption Fat intake: AF2 consumption
r = 0.395 0.364 r = 0.522 0.522 r =-0.393 -0.510
0.175 0.522 0.043
Partial correlation coefficient Breast ca. increasing ratio: fat intake Breast ca. increasing ratio: AF2 consumption
c = 0.765 r = 0.717
0.859 0.883
0.179 0.523
Multiple correlation coefftcient Breast ca. increasing ratio: fat intake + AF2 consumption
r = 0.836
0.900
0.544
U.S.-JAPAN
BREAST
CANCER
AND
DIET
CONFERENCE
191
. l’ -cZGiKJ KI TAO,' ,I’ KYUSH”, / I’ *
1.5 -
,’
1.4 ,’
IN
KANT0 .
/
BREAST
HOKKAIDO
1,’
INCREASE
” 8’
’ TOKAI. . . FANTOI KINKJ I, .
1.3 -
CANCER
,’
II
/
KINK,
MORTALITY
I
,’
.?OHOKU (ZIG&
l**
/
-
’
p&
,,I’ r =
l.l-
/’ -
0%’
0.900
,/I’
~HOKURIKlf’ ~~4IKOK” 1.1 1.2 1.3 1.4 Y = -O-M9 + 0.036(~) + 5.312hc) ‘ANNF;;,
(AFS
1.5
CONSUMPTION)
FIG. 18. Daily amount of animal fat intake (1%8), daily amount of AF2 consumption (1968), and ratio of increase in breast cancer mortality rate (1969- 1974), Japan.
DISCUSSION
AND SUMMARY
Breast cancer frequency is still quite low in Japanese women. However, breast cancer mortality and morbidity rates are on a steady increase in Japan in recent years. Most probably this increase in breast cancer mortality and morbidity rates is the reflection of the increase in the amount of dietary fat intake, especially in CHllDREii
FIG. 19. Extent of change in heights and weights of Japanese women 1949 to 1973
192
TAKESHI
HIRAYAMA
TABLE
11
RELATIVE RISK OF BREAST CANCER BY WEIGHTS: RESULTS OF A CASE-CONTROL STUDY (NATIONAL CANCER CENTER HOSPITAL AND CANCER INSTITUTE HOSPITAL) 1975- 1976
Weights Low Age group
<39
Br. Ca.
19
Medium 38
Control Br. Ca.
34 47
so+
Control Br. Ca.
48 26
60+
Control Br. Ca.
61 13
70+
Control Br. Ca.
53 3
Control
22
Br. Ca.
97
65 85
55 21 (1.00)
Small and medium Tall
Control Br. Ca.
186 11
Control
32
Single
Br. Ca.
15
Control Br. Ca.
34 73
Divorced
Control Br. Ca.
129 20
Control
55
Br. Ca.
3
No
6
Br. Ca.
105 212
300 (1.78)**
70 43 38 (3.29)**
53 (2.52)* 19
458 100 123 48
14 (1.87)
23 130 (1.24) 186 35 (2.09)” 46 13
8 (3’97)* 70 (1.49) 83 24 (3.88)** 17
5 171 250 (1’38)*
65 273 398 79 118 22
6 (2.40)
(5.20)
(1.00) Control
39
65
202 46
(1.00) Control
(16.50)**
(1.31)
(1 .OO) Yes
130 17
4
138
(1 .w
Breast cancer in blood relatives
(3.40)**
(2.82) 13
(1.W Married
141 59
30 9
(1.00) Marital status
(2.63)*
(1.82)
(1.00)
151 89
25 25
47 5 (1.00)
Height
(1.39) 28 28
(1.49)
(1.W
120 171
21 39
75 35
Total
(0.60)
(1.13)
(1.00)
-
64
7 (1.05)
(1.W 40+
Heavy
5 102 1o3 (2.00)**”
16 378 565
U.S. -JAPAN
BREAST
CANCER
AND
DIET
193
CONFERENCE
TABLE 11 (Continued) Weights Small Premenopausal Br. Ca. women Control Postmenopausal Br. Ca. women Control Residence
Large cities
Br. Ca.
66
122 141 62
58 121 40
Villages
Control Br. Ca.
84 10
Control
13
Br. Ca.
29
145 73
>13
(1.74)‘;
Control Br. Ca.
54 35
Control Br. Ca.
49 24
Control Br. Ca.
45 12
Control Br. Ca.
38 8
Control
32
14
15
16
(1.00)
Higher than low weight women, significant at * 5% level. -.
26
112 176 99 (1.W
28 29 (1 .OS)
26 25
42 (1.21)
(1.04)
(1.OO)
17
(2.04)
37 20
59 33 59 33
224 50
24
85 44
(1.00)
315 162
7 (1.29)
(1.00)
188 (2,04)**
(1.98)”
(1.71) 59
(4,02)**
(3.85)“”
281 167 300
52 11
22 (1.00)
(3,76)*“::::
49 49
88 29 (1 .OO)
Age at menarche
48 (1.18)
(1 .OO)
233
53
82 (1.00)
Control Br. Ca.
55 63
114
Total
(1.05)
(1.72)*
(1.00) 133
Towns
45 (1.11)
(1.00) 85 42
Tall
Medium
136 86
(2.59)” 125 51
21 16 (3.38)’ 15 19 7
(10,g6)““:*
79 52 65
194
TAKESHI
HIRAYAMA
TABLE
12
RELATIVE RISK OF BREAST CANCER BY EXTENT OF OBESITY: RESULTS OF A CASE-CONTROL STUDY (NATIONAL CANCER CENTER HOSPITAL AND CANCER INSTITUTE HOSPITAL) 1975- 1976
Premenopause Thin
Postmenopause
30
Br. Ca.
15 (1.W
(1.00) Ordinary
Control Br. Ca.
51 137
Slightly obese
Control Br. Ca.
180 52
Obese
Control Br. Ca.
42 14
Control
8
99 96 (4.76)***
(1.29) 133 41
(4.51)***
(2.10)4 60 15
(12.38)***
(2.98)* 8
Numbers in parentheses indicate relative risk, higher than “thin” * 5% level. *** 0.1% level.
category, significant at
the form of pork, in recent years in Japan. The correlation study for 12 districts in Japan showed that dietary fat, compared with other nutritional elements, is most closely associated with the incidence of breast cancer. Further analysis revealed that this association with dietary fat is satisfactorily explained by the daily amount of pork intake. Selected epidemiological characteristics of breast cancer, such as urban-rural relationship, socioeconomic variation, geographic variation, and annual trend, are all found to be explained by such a diet factor. Japanese migrants show much elevated breast cancer incidence rates (Fig. 1). It is well known that the diet of such migrants is quite different from that of Japanese in Japan. They are also much taller and heavier than Japanese in Japan. The ratio of increase in breast cancer by districts in Japan is also shown to be closely correTABLE 13 THE RELATIVE RISK OF BREAST CANCER IN POSTMENOPAUSAL IN 12 GROUPS ACCORDING TO HEIGHT AND WEIGHF’
Height (cm) >I55
2.6 s: 3 c: 5
5.0 s:17 c:15
7.5 s:16 c:lO
11.5 s:13 c: 5
145- 154
1.5 s:15 c:44
3.3 s:40 c:53
4.2 s:25 c:26
5.5 s: 5 c: 4
<144
1.0 s: 5 c:22
2.6 s: 7 c:12
4.4 s: 4 c: 4
45-54
55-64
r65
WOMEN
Weight (kg)
0 Relative to a risk of 1.0 for patients with both height <145 cm and weight <45 kg. s: Breast cancer group. c: Control.
U.S.-JAPAN
BREAST
CANCER
DIET
195
CONFERENCE
lated with the amount of animal fat intake and AF2 intake, a known carcinogenic food additive consumed widely between 1%5 and 1975. Although Al?2 was banned in 1975, a careful surveillance of its long-term effect is necessary. An intensive study on the underlying mechanism of such association by a multidisciplinary task force (7) was also strongly recommended. TABLE
14
BREAST CANCER PREVALENCE RATE BY HEIGHT AND WEIGHT: RESULTS MASS SCREENING IN TOKUSHIMA PREFECTURE, JAPAN, 1973-1976
Height (cm)
OF
Weight (kg) <59
65+
60+
Total
160+
- 1 (0.18%) 551
.-!- (0.64%) 156
? (1.75%) 114
150+
10 (0.11%) 8831
3 (0.26%) 1146
Q” (0.76%) 526
17 (0.16%) 10503
<149
- 9 (0.10%) 8933
&
&
(0.25%)
~ 10 (0.11%) 9481
Total
20 (0.11%) 18315
v-r? (0.29%) 1708
-6
(0.77%)
31
(0.25%)
782
&
20805
(0.49%)
(0.15%)
n Higher than lowest category (significant at 0.1% level).
REFERENCES 1. Buell. P. Changing incidence of breast cancer in Japanese-American women. J. Nat/. Cancer Inst. 51, 1479-1483 (1973). 2. De Waard, F. The epidemiology of breast cancer; review and prospects. Int. J. Cancer 4,577-586 (1969). 3. De Waard, F. and Baanders-van Halejijn, E. A. A prospective study in general practice on breast cancer risk in post-menopausal women. Int. J. Cancer 14, 153- 160 (1974). 4. De Waard, F. Breast cancer incidence and nutritional status with particular reference to body weight and height. Cancer Res. 23, 3351-3356 (1975). 5. Drasar, B. S., and Irving, D. Environmental factors and cancer of the colon and breast. Brit. J. Cancer 27, 167- 172 (1973). 6. Hems, G. Epidemiological characteristics of breast cancer in middle and late age. &if. J. Cancer 24, 226-234 (1970). 7. Hill, M. J., Goddard, P., and Williams, R. E. Gut bacteria and aetiology of cancer of the breast. Lancer 2, 472-473 (1971). 8. Hirayama, T., and Wynder, E. L. A study of the epidemiology of cancer of the breast. II. The influence of hysterectomy. Cancer 15, 28-38 (1%2). 9. Hirayama, T. Prospective studies on cancer epidemiology based on census population of Japan. Excerpta Med. 3, 26-35 (1975). 10. MacMahon, B., Cole, P., and Brown, J. Etiology of human breast cancer; a review. J. Nrrf. Cancer Inst. 50, 2 l-42 (1973). 11. Takatani, O., Wakabayashi, Y., and Hirayama, T. Clinical epidemiology of breast cancer with special reference to the relationship with body size. A comparison of 500 breast cancer cases and 1508 controls in Tokyo. Japanese J. C/in. Oncol., in press. 12. Takayama, S., and Kuwabara, N. The production of skeletal muscle atrophy and mammary tumors in rats by feeding 2-(2-furyl)-3-(5-nitro-2-furyl) acrylamide. Toxirol. Letf. 1, I I - 16 (1977). 13. Wynder, E. L., Brass, I. J., and Hirayama, T. A study of the epidemiology of cancer of the breast. Cancer 13, 559-601 (1960).
MEDICINE
7, 173- 195 (1978)
Epidemiology
of Breast Cancer with Special Reference to the Role of Diet1 TAKESHI
Epidemiology
Division,
National
HIRAYAMA
Cancer Center Research Chuo-ku, Tokyo, Japan
Institute,
Tsukiji 5-Chome,
Breast cancer is still relatively infrequent in Japan. However, both mortality and morbidity rates have sharply increased in recent years, especially in ages 45-59. The risk was noted to be 8.5 times higher in women of high socioeconomic strata eating meat daily compared with women of low socioeconomic strata who do not eat meat daily, when 142,857women aged 40 years were followed for 10 years. A high positive correlation was found between per capita fat intake and adjusted death rates of breast cancer in different districts of Japan. It was estimated that the breast cancer death rate will rise to the U.S. level when Japanese dietary fat intake approaches present day U.S. levels. The close correlation with fat intake was noted to come mainly from the consumption of pork and animal fat. The ratio of recent increase in breast cancer death rates was also found to be under the combined influence of animal fat and AF2, a highly mutagenic food additive widely used in Japan from 1965to 1975 and shown to produce mammary carcinoma in rats. A series of case-control studies reveals the higher risk of breast cancer with the increase in body size especially in postmenopausal women. The recent breast cancer increase could therefore be a reflection of the fact that women in Japan are becoming heavier, especially after age 30.
INTRODUCTION In order to explain the exceedingly low incidence of breast cancer in Japan, many epidemiological studies were conducted in the past with regard to incidence in migrants (l), reproductive histories (6, 8, 10, 1l), diet (5), and body size (2-4). Both patterns of breast cancer occurrence and background situations are, however, rapidly changing in Japan. The purpose of this paper is to discuss the possible reasons for such lower incidence and also for the recent increase of breast cancer in Japan, with special reference to the role of dietary fat intake and body size based on a series of epidemiological studies conducted in recent years in Japan. MATERIALS Vital statistics in Japan from 1955 to 1975 and results of the National Nutritional Survey from 1949 to 1973 provided the data for this presentation. A population prospective study on the health consequences of selected risk factors has been in progress in Japan since the fall of 1965 (9). In total, 142,857females, aged 40 years and over, in 29 Health Center Districts in Japan, interviewed from October 1 to December 31, 1%5, have been followed by establishing a record linkage system between the risk factor records, a current residence list obtained by specially planned annual census, and death certificates. The 10 year follow-up results of this ’ Presented at the Breast Cancer, Diet and Epidemiology Meeting, sponsored by the U.S.-Japan Cooperative Cancer Research Program, NCI-JSPS. Seattle, Washington. March 14- 15, 1977. 173 0091-7435/78/0072-0173$02.00/O Copyright 411 right\
c 197X hy Academic Pres\. Inc of reproductmn xn any form rewrved
174
TAKESHI
HIRAYAMA
study were used as the material. Out of 1,330,382 person-years of observation, 142 women died of breast cancer. The SMR for these women was calculated by various risk factors. RESULTS A. Descriptive Epidemiology Breast cancer is known to be infrequent in Japan. Out of 80 cancer registries in the world, Okayama, Miyagi, and Osaka ranked 74th, 7&h, and 79th, respectively, in the list arranged according to the magnitude of breast cancer incidence rate (Fig. 1). Both mortality (Table 1, Fig. 2) and morbidity rates (Fig. 3) for breast cancer are, however, sharply increasing. The number of annual breast cancer deaths doubled during the past 20 years in Japan: 1572 in 1955 and 3262 in 1975 (Table 2, Fig. 4). The death rate has also steadily increased in recent years: 3.5 and 5.8 per 100,000 in 1955 and 1975, respectively. The extent of increase by age groups is shown in Fig. 5. Breast cancer death rates, especially at postmenopausal age, are higher in large cities (Figs. 6 and 7). The ratio of increase is also highest in large cities (Fig. 8). Breast cancer is known to be quite frequent in the higher socioeconomic strata. SMRs for breast cancer in the current prospective study were 23.6 for the highest strata (professional, managers), 13.7 for the middle strata (clerks, sales, service, transportation, and factory workers), and 8.9 for the lowest strata (agriculture, fishery, miners). B. Analytic Epidemiology 1. Reproductive history. As shown in Fig. 9, the age-specific mortality rate for single women in Japan is quite close to the rate for U.S. white women, while that for married women is far lower than U.S. figures. A series of retrospective studies and the on-going prospective study also clearly showed a strikingly higher mortality rate for breast cancer in single women. It appeared that if women marry, even if they are nonparous, the risk of developing breast cancer goes down. The risk further goes down with the increase in number of children, The effect is independent of the effect of age at first marriage (Fig. 10). The striking international variation in breast cancer incidence rate is, however, not explained by the difference in factors related to reproductive history. 2. Dietary fat and meat intake. The promoting influence of diet, particularly dietary fat, was analyzed. The risk-enhancing effect of daily intake of meat was shown by our on-going census population-based prospective study in Japan. A higher standardized mortality ratio of breast cancer was observed in women who ate meat daily, SMR being 1.26 and 2.38, respectively, in age groups 40-54 and 55 and over compared with non- or occasional meat eaters (Table 3). It was 5.90 in women of high socioeconomic status, 1.94 in women of middle socioeconomic status, and 1.10 in women of low socioeconomic status (Table 4). A similar relationship was also observed in another population study in Japan. A higher breast cancer incidence rate was observed in women who eat meat, eggs, butter, and cheese daily in the Adult Health Survey in Hiroshima (Kato) (Table 5). A similar phenomenon was also shown by a correlation study. A high correlation coefficient (Y = 0.842) was observed between dietary fat intake and breast cancer adjusted mortality rates in 12 districts in Japan (Fig. 11). Such a high
U.S.-JAPAN
BREAST
(STANDARDIZED:
CANCER
AND DIET CONFERENCE
175
WORLD POPlJLATION)
FIG. I. Age standardized breast cancer incidence rate [Cancer Incidence in Five Continents, Vol. III, 1976.
40-44 45-49 50-54 55-59 60-64 65-69
40-44 45-49 50-54 55-59 60-64 65-69
Death rate Per 100,000
Ratio to 1955 death rate
Age
100.0 100.0 100.0 100.0 100.0 100.0
6.4 8.7 10.1 11.6 13.6 14.7
1955
103.1 86.2 101.0 103.4 85.3 91.8
6.6 7.5 10.2 12.0 11.6 13.5
‘56
100.0 87.4 96.0 86.2 83.1 72.1
92.2 120.7 113.9 105.2 89.7 85.7
5.9 10.5 11.5 12.2 12.2 12.6
‘58
TREND
6.4 7.6 9.7 10.0 11.3 10.6
‘57
ANNUAL
120.3 93.1 107.9 95.7 84.6 77.6
7.7 8.1 10.9 11.1 11.5 11.4
‘59
100.0 109.2 95.0 95.7 75.7 81.0
6.4 9.5 9.6 11.5 10.3 11.9
‘60
%.9 110.3 113.9 96.6 74.3 88.4
6.2 9.6 11.5 11.2 10.1 13.0
‘61
OF AGE-SPECIFIC
103.1 109.2 103.0 96.6 89.0 83.7
6.6 9.5 10.4 11.7 12.1 12.3
‘62
DEATH
109.4 111.5 102.0 100.9 83.1 76.2
7.0 9.7 10.3 12.1 11.3 11.2
‘63
RATE
TABLE
103.1 111.5 119.8 104.3 69.9 81.0
6.6 9.1 12.1 11.1 9.5 11.9
‘64
106.3 108.0 124.8 108.6 87.5 87.8
6.8 9.4 12.6 12.6 11.9 12.9
‘65
FOR BREAST
1
115.6 113.8 122.8 114.7 94.9 78.9
7.4 9.9 12.4 13.3 12.9 11.6
‘66 6.9 9.9 12.2 12.5 12.9 11.5
‘67
100.0 121.8 122.8 120.7 102.2 87.8
6.4 10.6 12.4 14.0 13.9 12.9
‘68
IN JAPAN,
107.8 113.8 120.8 107.8 94.9 78.2
CANCER
103.1 114.9 120.8 107.8 86.8 79.6
6.6 10.0 12.2 12.5 11.8 11.7
‘69
112.5 121.8 130.7 122.4 102.9 85.0
7.2 10.6 13.2 14.2 14.0 12.5
‘70
1955-1975
118.8 131.0 147.5 127.6 106.6 95.9
7.6 11.4 14.9 14.8 14.5 14.1
‘71
123.4 133.3 147.5 129.3 102.9 91.8
7.9 11.6 14.9 15.0 14.0 13.5
‘72
132.8 132.2 146.5 126.7 114.0 104.1
8.5 11.5 14.8 14.7 15.5 15.3
‘73
121.9 151.7 151.5 141.4 106.6 93.9
7.8 13.2 15.3 16.4 14.5 13.8
‘74
134.4 141.4 168.3 142.2 116.2 98.6
8.6 12.3 17.0 16.5 15.8 14.5
‘75
5
2
$
E
; R g z
U.S.-JAPAN
BREAST CANCER AND DIET CONFERENCE
177
150 140 130 l-20 110 100 90 80 70 a 65-69
‘....‘....‘......d
1955
60
65
70
75 1955 60
-
65
70
751955
60
65
70
75
CALENDARYEARS
FIG. 2. Annual trend of age-specific death rate for breast cancer in Japan, 1955- 1975(1955= 100).
FIG. 3. Trends of age-adjusted cancer incidence rates by selected primary site (Osaka).
178
TAKESHI
HIRAYAMA
TABLE 2 CHANGE
Year 1909 1910 1911 1912 1913 1914 1915 1916 1917 1918 1919 1920 1921 1922 1923 1924 192.5 1926 1927 1928 1929 1930 1931 1932 1933 1934 193.5 1936 1937 1938 1939 1940 1941 1942
IN NUMBER
OF BREAST
CANCER
DEATHS
1909- 1976, JAPAN
Number of deaths 441 437 481 511 504 507 549 537 606 552 535 592 542 570 650 616 647 647 660 708 703 716 752 764 813 855 820 907 943 919 945 934 904 993
(FEMALE)
Number of deaths 1943 1944 1945 1946 1947 1948 1949 1950 1951 1952 1953 1954 1955 1956 1957 1958 1959 1960 1961 1962 1963 1964 1965 1966 1967 1968 1969 1970 1971 1972 1973 1974 1975 1976
969 -
1192 1235 1370 1419 1402 1446 1452 1526 1572 1544 1458 1692 1652 1683 1741 1740 1857 1853 1966 2100 2107 2248 2208 2486 2689 2762 2995 3058 3262 3346
correlation coefficient was not observed with any other nutritional element (Table 6).
The amount of intake of dietary fat in Japan and in the U.S.A. is 52 and 155 in 1973, respectively. It was 23 and 143, respectively, in 1957-1959. Among each nutritional element, dietary fat intake showed the most striking increase in Japan in recent years (Fig. 12). It is of interest to note that the U.S. breast cancer mortality rate was expected
U.S.-JAPAN
BREAST
CANCER
AND
DIET
CONFERENCE
179
3262
3ooc
250C
2ooc
% Y 5 0.
15oc
f 2 a "0
1ooc
z 2 2 5oc
(
I
950
55
I
65
60
1
70
75
YEAR
FIG. 4. Change in number of annual breast cancer deaths, 1950- 1975, Japan.
to be 20 per 100,000 while the actual rate was 18 (adjusted to 1960 population in Japan) by extrapolating the regression line of dietary fat-breast cancer correlation in Japan. Among the food items, the highest correlation was found with the per capita amount of pork intake (Y = 0.895) (Table 7, Fig. 13) and next came the amount of animal fat intake (r = 0.675). The partial correlation study revealed a near disappearance of the above mentioned high correlation between breast cancer mortality rate and dietary fat intake when the effect of correlation with pork intake was taken out. On the other hand, the correlation of breast cancer mortality rate with pork intake still remained high (r = 0.573) even if the influence of dietary fat was removed by calculating partial correlation coefficient (Table 7).
180
TAKESHI
HIRAYAMA
975
974
950-52
937-40
10
20
30 Age
40
50
60
70
80
90
groups
FIG. 5. Age-specific death rate for breast cancer in different years, Japan (female).
150140
150'
l(r5
LUNG CANCER
130 ’
BREAST CANCER
140’ 130
120
120 *
120
110 ’ 100!ETRO- CITIES POCITAN AREAS
COUNTIES
1CKl
CITIES COUNTIES
FIG. 6. Adjusted death rates for cancer of all sites and each site in metropolitan areas, cities, and counties in 1960 and 1970 (ratio to death rate in counties).
U.S. -JAPAN
BREAST
CANCER
AND
DIET
CONFERENCE
181 AREAS
DEATH RATE PER 100,000
FIG.
7. Age specific death rate for breast cancer by urban-rural 160,
difference, 1970, Japan,
LUN6CANCER 156,~
BREAST CANCER 116.7
100
WLITANCITIES CWNTIES AREAS
RETRD- CITIES COUNTIES PDLITAN
FIG. 8. Change in the adjusted death rates for cancer of all sites and each site in metropolitan areas. cities, and counties in Japan (ratio of death rates in 1970 to those in 1960).
MEAT
INTAKE
AND BREAST
Meat
intake 40-54
Daily
Occasional,
CANCER
Obs. person-
years
TABLE 3 RATE, 1966-1975,
DEATH
No. of breast
7 65
27,402 540,265
7 60
rare, none
55+
Daily Occasional, rare, none
Crude death rate
cancer death
51.477 688,590
PROSPECTIVF.
Standardized death rate
1.30
1.26 25.90
25.55
10.89
Il.11 Ratio
JAPAS
il.84 9.43
12.18 9.40
Ratio
STUDY,
2.30
2.38
182
TAKESHI
HIRAYAMA
TABLE 4 SMR
FOR BREAST CANCER BY FREQUENCY OF MEAT SOCIOECONOMIC STATUS, PROSPECTIVE STUDY
INTAKE
AND BY
(1966- 1975)
Frequency of meat intake Socioeconomic status
Occupational category
Daily
Occasional, rare or none
Ratio
High
Professional Managers
85.35
15.46
5.90
Middle
Sales Clerks Service
19.33
9.94
1.94
Low
Factory Transportation Miners Farmers
11.04
10.04
1.10
TABLE 5 BREAST CANCER HIROSHIMA,
INCIDENCE
1965-
RATE BY FREQUENCY OF FOOD TAKEN, 1974, ADULT HEALTH STUDY SAMPLE”
Frequency of food taken Food Meat
Total Case
30
Less than once a week 2
2-4 times a week
Control Em
Case
3992
696
2304
30
13
6
Butter Cheese
Case
316
30
9
Case
3992
2112
30
6
Control Case
872
0.89% (2.10) 1008 9
15 0.67% (0.76)
676
2232
30
18
10
2052
9 1.38% (3.23)
3988
3992
0.90% (2.86) 2568
12
0.88% (1.W Control
23
1104
0.89% (1.00) Ham Sausage
992 0.54% (1.91)
0.43% (1.00) Control
Fish
3982
1.11% (3.83)
0.74% (2.55)
0.32% (1.W Control
11
17 0.29% (1.OO)
Almost daily
0.83% (0.94) 1080 2 0.47% (0.73)
0.66% (0.75) 1512
428
a Breast cancer cases: 1965- 1974; control: adult health study sample examined in 1965-66.
U.S. -JAPAN
BREAST
CANCER
AND
loo I'
,--
DIET
183
CONFERENCE
.’ _--*.--
SINGLE JAPAN(1970)
/I
U.S. WHITES /' (1950-67) ,/'-
10
I
I :4’ ::: I:1’ :Y
MORTALIT RATE PER 100,000
20 25 30 35 40 45 50 55 60 65 70 AGEGROUPS
FIG. 9. Breast cancer age-specific mortality rate by marital status, 1970, Japan.
NUMBER OF 0 CHILDREN
5
IO
I5
20
25
35
30
40
45 4.3
4 SINGLE PURRIED
3 OR NORE AGE AT FIRST
@ARRIAGE
m J
25I
-
24
FIG. 10. SMR for breast cancer by number of children and by age at first marriage, prospective study (1966- 1975, Japan) SMR per 100,000.
184
TAKESHI
HIRAYAMA
TABLE CORRELATION
6 MORTALITY
COEFFICIENT FOR BREAST CANCER ADJUSTED RATE AND NUTRITIONAL INTAKE, 1970, JAPAN
Partial correlation coefficient (1) calorie (2) Animal protein (3) Vegetable protein (4) Fat (5) Carbohydrate (6) Calcium (7) Vitamin A (8) Vitamin B, (9) Vitamin B, (IO) Vitamin C
r =
0.145
0.336
r = 0.361 r = -0.010 r = 0.842 r = -0.412 r = 0.205 r = 0.552 r= 0.449
0.421 0.846
0.851
-0.215 0.850
0.816 -0.215
0.931
0.800
0.921
0.747
0.823
-0.749 0.300 -0.741
r =
0.601
r =
0.317
0.170 -0.028
Significant at 1% level.
This means that in the case of Japanese women, the amount of pork eaten, which is much cheaper than beef, is quite important in raising the incidence of breast cancer (Fig. 14). The national nutritional survey showed a striking increase in per capita intake of pork in Japanese people in recent years (Fig. 15). In Fig. 16, correlation patterns between breast cancer mortality rate and dietary fat, pork intake, and beef intake are summarized. Figure 17 and Table 8 show international correlation between pork intake and breast cancer adjusted mortality rate. 3. Factors responsible for the recent increase. The statistical analysis clearly shows that the ratio of increase in the breast cancer death rate is closely as-
. uwrol
l@wJ KIN0
' KITA KMlW iuimll
I 2.51 35
R’0.W l
WaMJ
ul
45
PERCAPITAWILY FAT his
FIG. 11. Breast cancer mortality
I 5l
1 55
( G)
rate and daily fat intake for 12 blocks inJapan,
1970.
U.S.-JAPAN
BREAST
CANCER
AND
DIET
185
CONFERENCE
FAT 257 25
/
20 ANIML PROTEIN188
15 RATIO TO AJ’tiNT OF INTAKE IN 1955
/.’
.,
TOTALPROTEIN121
lol
0
,*..‘....I.-..fi... 1960
1965 YEARS
1970
FIG. 12. Change in amount of intake of selected nutrients in Japan (1955- 1973) 5.5
. KANT0
.
5.0'
2 z ; t" ggt” 9 !it
2 2
HOKKAIW
4.5-
. 4.0. 4.0.
KINK1
TOHOK” TOHOKU TOKAI I.. ’ . HOKURIKU*
SOUTH
3.5. 3.5.
. KYUSHU .
KINK1
Dz : : 5
5 2 $$
KANT0 II
IItI
’
.. CHUGOKU CHUGOKU
3.0 3.0-
NORTH KYUSHU
r = 0,895
. I 2.5' 2.5-
0
SHIKOKU
10 PORK PER CAPITA DAILY
20
30
INTAKE(G)
FIG. 13. Breast cancer and pork intake, 1970, Japan.
I
186
TAKESHI
HIRAYAMA
TABLE 7 CORRELATION COEFFICIENT FOR BREAST CANCER ADJUSTED MORTALITY AND DIETARY INTAKE (PER CAPITA INTAKE), JAPAN, 1970
RATE
(1) (2) (3) (4) (5) (6) (7) (8) (9) (10) (11) (12) (13) (14) (15) (16) (17) (18)
Breast canceIQ Fat Food of animal origin Food of vegetable origin Cereals Rice Barley Wheat Bread Seeds and nuts Potatoes Sugars Confectionaries Oils and fats Butter Margarine Vegetable oil Animal fat, lard
0.842 0.439 0.380 -0.522 -0.496 -0.207 0.378 0.224 0.174 0.231 -0.505 0.529 0.628 0.626 0.383 0.252 0.675
0.818 0.820 0.805 0.792 0.876 0.813 0.836 0.880 0.847 0.885 0.791 0.811 0.800 0.834 0.907 0.918
0.286 0.200 -0.344 -0.194 -0.482 -0.021 0.129 -0.499 0.280 -0.666 0.269 -0.702 0.498 0.327 -0.646 0.840
(19) (20) (21) (22) (23) (24) (25) (26) (27) (28) (29) (30) (31)
Mayonnaise Beans Fruits Green and yellow vegetables Other vegetables Dried vegetables Salted vegetables Seaweeds Fish and shellfish Fish sausage Meat, poultry. and whale Beef Pork
0.363 0.016 0.060 0.225 0.271 -0.572 0.516 0.053 0.235 -0.212 0.286 -0.487 0.895
0.817 0.857 0.850 0.841 0.882 0.762 0.777 0.843 0.874 0.836 0.827 0.802 0.129
0.054 -0.295 0.236 0.207 -0.531 -0.163 0.020 -0.044 0.484 0.090 -0.011 -0.255 0.573
Chicken Other meats Ham sausage Canned and other meat products (36) Eggs (37) Milk and milk products (38) Milk (39) Cheese (40) Condensed and powdered milk
-0.304 0.031 0.408 0.495 -0.395 0.417 0.361 0.733 0.502
0.842 0.848 0.815 0.842 0.857 0.876 0.816 0.791 0.847
-0.306 0.182 0.189 0.495 -0.477 0.584 0.031 0.635 0.523
(32) (33) (34) (35)
rl.n
a Adjusted mortality rate.
sociated with both daily amount of animal fat intake (r = 0.364) and daily AF2 consumption (r = 0.522) (Table 9). AF2 is a highly mutagenic chemical widely used as a food additive for fish meal, ham, sausages, bean curd, etc. in Japan from 1965 to 1975. The highest correlation was observed when these two factors were combined (r = 0.900) (Table 10, Fig. 18). In view of the high yield of carcinoma of the breast in rats fed an AFZcontaining diet (12), it is most likely that AF2 also
U.S. -JAPAN
BREAST CANCER AND DIET CONFERENCE
5.5
187
. KANT0
I
.
5,o
HOKKAIDO
t
‘KANT0 TOHOKU KINK1
ltt
TOKAI .
I
l . l HOKURIKU
SOiTH KYUSHU KINK1
. NORTH KYUSHU
n’
.
r = 0.942
CHUGOKU
. SHIKOKU I
2.5
4
3.0 EXPECTED
3.5
4.0
RATE POLK AND
4.5
5.0
5.5
LARDINTAKE
Y = 2,662 + 0.0795(+ 2.5gSt FIG. 14. Breast cancer and pork and lard intake, 1970, Japan.
plays a role in promoting breast cancer risk in women in Japan in addition to the influence of dietary fat. 4. Body size. A clear-cut tendency of higher risk with increase in body size was observed in a case-control study carried out on patients in the National Cancer Center Hospital and the Cancer Institute Hospital in 1975- 1976 (1). The comparison of cases and controls revealed a significantly higher risk for breast cancer in heavy (5% or more heavier than national average) women aged 50 and over. (Table 11). Tall women with medium weight also showed higher risk. The effect of
TABLE 8 BREAST CANCER ADJUSTED MORTALITY RATE
AND
BEEF AND Pow
World, 1964- 1965 Japan, 1970 Breast cancer (1) and beef (2) Breast cancer (1) and pork (3) Beef (2) and pork (3) Partial correlation Breast cancer (1) and beef (2) Breast cancer (1) and pork (3) (I Beef less than 54 g per day. b Beef more than 55 g per day.
r,.* = -0.487 r,.3 = +0.895
rp.3 = -0.527 r 12Y13r 23 = -0.042 rl.3y1.2r1.3 = +0.861
28 countries”
12 countries?
+0.708 +0.767 +0.492
+o. 145 +0.213 -0.194
+0..594 +0.684
+o. 194 +0.248
188
TAKESHI
HIRAYAMA
YEARS
FIG. 15. Change in amount of intake of selected food in Japan (1960, 1966-1973) (meat, fats, and oils).
body size on breast cancer risk was similar in large cities, towns, and villages, in women with or without a family history (blood relatives) of breast cancer. The effect of body size is more striking in postmenopausal women, in single and divorced women, and in women with later age at menarche. Compared with thin women, obese women showed a significantly higher risk (Table 12). The relative risk of breast cancer in postmenopausal women by height and weight is shown in Table 13. The risk is 11.5 times higher in tall (over 155 cm) and heavy women (over 65 kg) than in small women. Similar results were obtained by a cross-sectional population study. In Tokushima Prefecture, breast cancer mass screening was carried out for 20,805 women over age 30 (Okazaki). The prevalence rates for breast cancer are noted to be significantly higher in women 160 cm tall or more and weighing 65 kg or more,
U.S. -JAPAN
BREAST
CANCER
AND
DIET
SOCIO-ECMUW
189
CONFERENCE
GEOGRAPHY
r - 0.895
3
ANNUAL TREND
s I
J
FIG. 16. Correlation between pork intake and breast cancer mortality rate, Japan. Breast cancer adjusted mortality rate. Pork per capita daily intake (G).
l
.
IRELAND
l
SWEDEN l
ITALY
l
. CZECHOSLOVAKIA
E z a s
PANAM;\ GREECE
r, ARAB U.R. ,I ISRAEL J, SRI LANKA
POLAND .ROUMANIA l YUGOSLAVIA
BULGbuA
.
J;pAN
PHtLIPPINES l
= = 0.767
.
MEXICO
EL SALVADOR l THAILAND
l
0
.
VENEZVELA 1 CHILE SPAIN,.
lo-
FORMOSA , 10
30
20 PORK PER CAPITA
FIG.
AUSTRIA
NORWAY
.
y
DENMARK
DAILY
INTAKE
40
(G)
17. Breast cancer and pork intake in 28 countries, 1%4- 1965(beef less than 54 g per day)
190
TAKESHI
HIRAYAMA
TABLE 9 DAILY
AMOUNT OF FAT INTAKE (1968), DAILY RATIO OF INCREASE IN BREAST CANCER
Breast cancer adjusted death rate per 100,000
Hokkaido Tohoku Kanto I Kanto II Hokuriku Tokai Kinki I Kinki II Chugoku Shikoku Kita Kyushu Minami Kyushu
AMOUNT OF AF2 CONSUMPTION (1968), MORTALITY RATE (1969- 1974), JAPAN
Ratio of increase 1974
AND
Per capita per day
1969
1974
1969
Total fat 1968
4.08 3.79 3.87 3.75 3.85 3.33 4.06 3.50 2.68 3.13 3.15 3.29
5.74 4.58 5.03 4.94 4.00 4.33 5.12 4.50 4.02 3.25 4.56 3.92
1.41 1.21 1.30 1.32 1.04 1.30 1.26 1.29 1.50 1.04 1.45 1.19
47.1 47.3 58.4 51.9 46.8 46.7 50.3 43.1 50.6 42.7 48.7 46.3
Animal fat 1968
Vegetable fat 1968
AF2 consumption 1968
20.5 16.6 28.9 20.6 18.7 21.7 25.2 19.2 21.7 16.8 20.0 19.6
26.6 30.7 29.5 31.3 28.1 25.0 25.2 23.9 28.9 25.9 28.7 26.7
0.177 0.157 0.120 0.164 0.135 0.157 0.120 0.176 0.186 0.168 0.205 0.148
risk being 17.5 times greater than for women shorter than 149 cm and weighing less than 59 kg (Table 14). C. Operational
Epidemiology
As shown in Fig. 19, a clear-cut tendency towards weight increase is observed in women after age 30 during the past 20 years in Japan. To prevent further increase in breast cancer incidence in Japan, since it does not appear easy to modify factors related to reproductive history, it is of urgent necessity to alert the government, the public, and individuals to the possible danger of excess dietary fat and resulting obesity. It is recommended that dietary goals be established in Japan, as has been done in the U.S. TABLE RATIO
OF INCREASE
IN BREAST FAT INTAKE
CANCER
(1968)
10
MORTALITY RATE (1969-1974) AND DAILY AND AF2 CONSUMPTION (1%8), JAPAN
Total fat
AMOUNT
Animal fat
OF
Vegetable fat
Simple correlation coefticient Breast ca. increasing ratio: fat intake Breast ca. increasing ratio: AF2 consumption Fat intake: AF2 consumption
r = 0.395 0.364 r = 0.522 0.522 r =-0.393 -0.510
0.175 0.522 0.043
Partial correlation coefficient Breast ca. increasing ratio: fat intake Breast ca. increasing ratio: AF2 consumption
c = 0.765 r = 0.717
0.859 0.883
0.179 0.523
Multiple correlation coefftcient Breast ca. increasing ratio: fat intake + AF2 consumption
r = 0.836
0.900
0.544
U.S.-JAPAN
BREAST
CANCER
AND
DIET
CONFERENCE
191
. l’ -cZGiKJ KI TAO,' ,I’ KYUSH”, / I’ *
1.5 -
,’
1.4 ,’
IN
KANT0 .
/
BREAST
HOKKAIDO
1,’
INCREASE
” 8’
’ TOKAI. . . FANTOI KINKJ I, .
1.3 -
CANCER
,’
II
/
KINK,
MORTALITY
I
,’
.?OHOKU (ZIG&
l**
/
-
’
p&
,,I’ r =
l.l-
/’ -
0%’
0.900
,/I’
~HOKURIKlf’ ~~4IKOK” 1.1 1.2 1.3 1.4 Y = -O-M9 + 0.036(~) + 5.312hc) ‘ANNF;;,
(AFS
1.5
CONSUMPTION)
FIG. 18. Daily amount of animal fat intake (1%8), daily amount of AF2 consumption (1968), and ratio of increase in breast cancer mortality rate (1969- 1974), Japan.
DISCUSSION
AND SUMMARY
Breast cancer frequency is still quite low in Japanese women. However, breast cancer mortality and morbidity rates are on a steady increase in Japan in recent years. Most probably this increase in breast cancer mortality and morbidity rates is the reflection of the increase in the amount of dietary fat intake, especially in CHllDREii
FIG. 19. Extent of change in heights and weights of Japanese women 1949 to 1973
192
TAKESHI
HIRAYAMA
TABLE
11
RELATIVE RISK OF BREAST CANCER BY WEIGHTS: RESULTS OF A CASE-CONTROL STUDY (NATIONAL CANCER CENTER HOSPITAL AND CANCER INSTITUTE HOSPITAL) 1975- 1976
Weights Low Age group
<39
Br. Ca.
19
Medium 38
Control Br. Ca.
34 47
so+
Control Br. Ca.
48 26
60+
Control Br. Ca.
61 13
70+
Control Br. Ca.
53 3
Control
22
Br. Ca.
97
65 85
55 21 (1.00)
Small and medium Tall
Control Br. Ca.
186 11
Control
32
Single
Br. Ca.
15
Control Br. Ca.
34 73
Divorced
Control Br. Ca.
129 20
Control
55
Br. Ca.
3
No
6
Br. Ca.
105 212
300 (1.78)**
70 43 38 (3.29)**
53 (2.52)* 19
458 100 123 48
14 (1.87)
23 130 (1.24) 186 35 (2.09)” 46 13
8 (3’97)* 70 (1.49) 83 24 (3.88)** 17
5 171 250 (1’38)*
65 273 398 79 118 22
6 (2.40)
(5.20)
(1.00) Control
39
65
202 46
(1.00) Control
(16.50)**
(1.31)
(1 .OO) Yes
130 17
4
138
(1 .w
Breast cancer in blood relatives
(3.40)**
(2.82) 13
(1.W Married
141 59
30 9
(1.00) Marital status
(2.63)*
(1.82)
(1.00)
151 89
25 25
47 5 (1.00)
Height
(1.39) 28 28
(1.49)
(1.W
120 171
21 39
75 35
Total
(0.60)
(1.13)
(1.00)
-
64
7 (1.05)
(1.W 40+
Heavy
5 102 1o3 (2.00)**”
16 378 565
U.S. -JAPAN
BREAST
CANCER
AND
DIET
193
CONFERENCE
TABLE 11 (Continued) Weights Small Premenopausal Br. Ca. women Control Postmenopausal Br. Ca. women Control Residence
Large cities
Br. Ca.
66
122 141 62
58 121 40
Villages
Control Br. Ca.
84 10
Control
13
Br. Ca.
29
145 73
>13
(1.74)‘;
Control Br. Ca.
54 35
Control Br. Ca.
49 24
Control Br. Ca.
45 12
Control Br. Ca.
38 8
Control
32
14
15
16
(1.00)
Higher than low weight women, significant at * 5% level. -.
26
112 176 99 (1.W
28 29 (1 .OS)
26 25
42 (1.21)
(1.04)
(1.OO)
17
(2.04)
37 20
59 33 59 33
224 50
24
85 44
(1.00)
315 162
7 (1.29)
(1.00)
188 (2,04)**
(1.98)”
(1.71) 59
(4,02)**
(3.85)“”
281 167 300
52 11
22 (1.00)
(3,76)*“::::
49 49
88 29 (1 .OO)
Age at menarche
48 (1.18)
(1 .OO)
233
53
82 (1.00)
Control Br. Ca.
55 63
114
Total
(1.05)
(1.72)*
(1.00) 133
Towns
45 (1.11)
(1.00) 85 42
Tall
Medium
136 86
(2.59)” 125 51
21 16 (3.38)’ 15 19 7
(10,g6)““:*
79 52 65
194
TAKESHI
HIRAYAMA
TABLE
12
RELATIVE RISK OF BREAST CANCER BY EXTENT OF OBESITY: RESULTS OF A CASE-CONTROL STUDY (NATIONAL CANCER CENTER HOSPITAL AND CANCER INSTITUTE HOSPITAL) 1975- 1976
Premenopause Thin
Postmenopause
30
Br. Ca.
15 (1.W
(1.00) Ordinary
Control Br. Ca.
51 137
Slightly obese
Control Br. Ca.
180 52
Obese
Control Br. Ca.
42 14
Control
8
99 96 (4.76)***
(1.29) 133 41
(4.51)***
(2.10)4 60 15
(12.38)***
(2.98)* 8
Numbers in parentheses indicate relative risk, higher than “thin” * 5% level. *** 0.1% level.
category, significant at
the form of pork, in recent years in Japan. The correlation study for 12 districts in Japan showed that dietary fat, compared with other nutritional elements, is most closely associated with the incidence of breast cancer. Further analysis revealed that this association with dietary fat is satisfactorily explained by the daily amount of pork intake. Selected epidemiological characteristics of breast cancer, such as urban-rural relationship, socioeconomic variation, geographic variation, and annual trend, are all found to be explained by such a diet factor. Japanese migrants show much elevated breast cancer incidence rates (Fig. 1). It is well known that the diet of such migrants is quite different from that of Japanese in Japan. They are also much taller and heavier than Japanese in Japan. The ratio of increase in breast cancer by districts in Japan is also shown to be closely correTABLE 13 THE RELATIVE RISK OF BREAST CANCER IN POSTMENOPAUSAL IN 12 GROUPS ACCORDING TO HEIGHT AND WEIGHF’
Height (cm) >I55
2.6 s: 3 c: 5
5.0 s:17 c:15
7.5 s:16 c:lO
11.5 s:13 c: 5
145- 154
1.5 s:15 c:44
3.3 s:40 c:53
4.2 s:25 c:26
5.5 s: 5 c: 4
<144
1.0 s: 5 c:22
2.6 s: 7 c:12
4.4 s: 4 c: 4
45-54
55-64
r65
WOMEN
Weight (kg)
0 Relative to a risk of 1.0 for patients with both height <145 cm and weight <45 kg. s: Breast cancer group. c: Control.
U.S.-JAPAN
BREAST
CANCER
DIET
195
CONFERENCE
lated with the amount of animal fat intake and AF2 intake, a known carcinogenic food additive consumed widely between 1%5 and 1975. Although Al?2 was banned in 1975, a careful surveillance of its long-term effect is necessary. An intensive study on the underlying mechanism of such association by a multidisciplinary task force (7) was also strongly recommended. TABLE
14
BREAST CANCER PREVALENCE RATE BY HEIGHT AND WEIGHT: RESULTS MASS SCREENING IN TOKUSHIMA PREFECTURE, JAPAN, 1973-1976
Height (cm)
OF
Weight (kg) <59
65+
60+
Total
160+
- 1 (0.18%) 551
.-!- (0.64%) 156
? (1.75%) 114
150+
10 (0.11%) 8831
3 (0.26%) 1146
Q” (0.76%) 526
17 (0.16%) 10503
<149
- 9 (0.10%) 8933
&
&
(0.25%)
~ 10 (0.11%) 9481
Total
20 (0.11%) 18315
v-r? (0.29%) 1708
-6
(0.77%)
31
(0.25%)
782
&
20805
(0.49%)
(0.15%)
n Higher than lowest category (significant at 0.1% level).
REFERENCES 1. Buell. P. Changing incidence of breast cancer in Japanese-American women. J. Nat/. Cancer Inst. 51, 1479-1483 (1973). 2. De Waard, F. The epidemiology of breast cancer; review and prospects. Int. J. Cancer 4,577-586 (1969). 3. De Waard, F. and Baanders-van Halejijn, E. A. A prospective study in general practice on breast cancer risk in post-menopausal women. Int. J. Cancer 14, 153- 160 (1974). 4. De Waard, F. Breast cancer incidence and nutritional status with particular reference to body weight and height. Cancer Res. 23, 3351-3356 (1975). 5. Drasar, B. S., and Irving, D. Environmental factors and cancer of the colon and breast. Brit. J. Cancer 27, 167- 172 (1973). 6. Hems, G. Epidemiological characteristics of breast cancer in middle and late age. &if. J. Cancer 24, 226-234 (1970). 7. Hill, M. J., Goddard, P., and Williams, R. E. Gut bacteria and aetiology of cancer of the breast. Lancer 2, 472-473 (1971). 8. Hirayama, T., and Wynder, E. L. A study of the epidemiology of cancer of the breast. II. The influence of hysterectomy. Cancer 15, 28-38 (1%2). 9. Hirayama, T. Prospective studies on cancer epidemiology based on census population of Japan. Excerpta Med. 3, 26-35 (1975). 10. MacMahon, B., Cole, P., and Brown, J. Etiology of human breast cancer; a review. J. Nrrf. Cancer Inst. 50, 2 l-42 (1973). 11. Takatani, O., Wakabayashi, Y., and Hirayama, T. Clinical epidemiology of breast cancer with special reference to the relationship with body size. A comparison of 500 breast cancer cases and 1508 controls in Tokyo. Japanese J. C/in. Oncol., in press. 12. Takayama, S., and Kuwabara, N. The production of skeletal muscle atrophy and mammary tumors in rats by feeding 2-(2-furyl)-3-(5-nitro-2-furyl) acrylamide. Toxirol. Letf. 1, I I - 16 (1977). 13. Wynder, E. L., Brass, I. J., and Hirayama, T. A study of the epidemiology of cancer of the breast. Cancer 13, 559-601 (1960).