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Diet and hormone levels in seventh-day adventist teenage girls
PREVENTIVE
MEDICINE
11,
103-107 (1982)
SHORT REPORT Diet and Hormone
Levels in Seventh-Day Teenage Girls’
Adventist
GREGORYE. GRAY,* PHYLLIS WILLIAMS,? VEEBAGERKINS,* JAMESB. BROWN,+ BRUCEARMSTRONG,!? ROLANDPHILLIPS,? JOHN T. CASAGRANDE,*MALCOLM C.PIKE,* AND BRIAN E. HENDERSON*~~ *Department of Family and Preventive Medicine, University of Southern California, 2025 Zonal Avenue, Los Angeles, California 90033, tSchoo1 of Health, Loma Linda University, Loma Linda, California 92354, $Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria, Australia, and $Public Health Department, Perth, Western Australia, Australia
Seventh-Day Adventist women in California have a decreased mortality rate from breast cancer. If this lower rate is due to the fact that many Adventists are lactoovovegetarians (“vegetarians”) then one may find reduced levels of suggested risk factors for breast cancer in such Adventists. We studied this by comparing plasma and urine sex hormone levels in Seventh-Day Adventist “vegetatarian” and “nonvegetarian” girls aged 14 to 17. No differences were found between the two groups in Day 11 estrogens and prolactin, or in Day 22 estrogens, progesterone, and prolactin. Mean heights, weights, and ages at menarche were also similar. The Adventists were similar in height, weight, and age at menarche, and had similar plasma hormone levels, when compared with non-Adventist “control” girls.
INTRODUCTION
Mortality data show that the risk of dying from breast cancer for California Seventh-Day Adventist women is approximately 30% lower than that of the general California population (17). It has been suggested that this reduced rate may be due to their dietary habits (17), as many of them are lacto-ovovegetarians. This possibility is supported by international comparisons where it has been demonstrated that animal fat and meat consumption is highly correlated with breast cancer rates (1, 4, 6), and both case-control and cohort studies have suggested that meat consumption may be a risk factor for breast cancer (8, 16). Although an association has not been found in all studies, recent expert reviews have concluded that age at menarche is an important risk factor for breast cancer (9, 13). Risk to breast cancer in rodents is affected by hormone levels, in particular estrogens and prolactin (2, IS), and there is some evidence supporting this in humans (9, 11, 13). We therefore reasoned that, if meat consumption per se is a risk factor for breast cancer, one might find differences in age at menarche and in plasma and urine hormone levels between meat eating and non-meat-eating Adventists.
’ Supported by Grants POl-CA-17054 and CA-14089 from the National Cancer Institute. * To whom reprint requests should be addressed. 103 0091-7435/82/010103-05$02.00/O Copyright @ 1982 by Academic Press, Inc. All rights of reproduction in any form reserved.
104
GRAY
ET AL.
METHODS With the help of six Adventist academies in Southern California, we sought white girls aged 14-17 who had menstrual cycles between 27 and 32 days in length, had never used oral contraceptives, had never been pregnant, did not take medication regularly, had no prior history of gynecological, endocrine, or neoplastic diseases, and were willing to have blood and urine specimens taken for hormone analysis. We identified 23 girls who had never eaten meat on a regular basis (“vegetarians”) and 26 who were eating meat, fish, or poultry at least weekly (“nonvegetarians”). These girls completed a detailed questionnaire on dietary habits. The dietary questionnaire grouped foods into 88 categories and included information on frequency of consumption and serving size. The caloric, protein, carbohydrate, and fat intakes were estimated from this detailed food frequency questionnaire using food composition data from the Extended Table of Nutrient Values (14, 15). Blood samples were collected in the homes of the subjects between 30 min and 2 hr after arising on Days 11 and 22 of the same menstrual cycle. The blood was collected into lo-ml tubes containing potassium ethylenediaminetetraacetate (EDTA). After centrifugation, the plasma was separated and stored in several aliquots at -20°C. Plasma levels of progesterone, prolactin, estrone (E,), and estradiol (E,) were measured on coded samples by Endocrine Sciences Laboratory, Tarzana, California, by means of radioimmunoassay. Overnight urine specimens (12-hr) were also collected, the collections ending on the mornings when the blood samples were drawn. The urine was treated with 15 ml of 20% acetic acid, divided into 25ml aliquots, and stored at -20°C. Aliquots of urine were coded and air freighted frozen in dry ice to Melbourne where urine levels of El, Ez, and estriol (Es) were measured by one of us (J. B.) using a method involving spectrophotofluorimetry and internal radioactive standards (3). Urine hormone concentrations were converted into absolute amounts by multiplying the concentration by the total volume of urine collected. Tests of statistical significance were calculated using the standard t test.
TABLE 1 MEAN ANTHROPOMETRIC MEASUREMENTS AND AGE AT MENARCHE OF SEVENTH-DAY ADVENTIST TEENAGE GIRLS”
“Vegetarians” Height (cm) Weight (kg) Quetelet’s index* Menarche (years) N n None of the differences between significant. * (Weight/height”) x 10,000.
165.2 57.2 20.9 12.6 23 the “vegetarians”
“Nonvegetarians” 164.7 58.7 21.6 12.5 26 and the “nonvegetarians”
Total 164.9 58.0 21.3 12.5 49 are statistically
HORMONE LEVELS IN SEVENTH-DAY
105
ADVENTISTS
RESULTS
“Vegetarians” and “nonvegetarians” did not differ in height, weight, or age at menarche (Table 1). The relative amounts of protein, fat, and carbohydrates [expressed as percentage of calories] consumed by “vegetarians” and “nonvegetarians” were all very similar (Table 2). The mean hormone levels are shown in Table 3. The levels are quite similar and no statistically significant differences were found.
TABLE 2 MEAN
DIETARY
INTAKES
OF SEVENTH-DAY
ADVENTIST
GIRLS
“Nonvegetarians”
“Vegetarians” Protein (% of calories) Fat (% of calories) Carbohydrates (% of calories) Fish (servings per week) Poultry (servings per week) Meat (servings per week) Eggs (per week) Milk (servings per day) Other dairy products (servings per week)
TEENAGE
Total
17.6 36.0 46.4 0 0 0 2.6 2.6
17.2 38.3 44.5 1.1 1.3 2.5 3.1 2.4
17.4 37.2 45.4 0.7 0.8 1.5 2.9 2.5
7.1
7.4
7.3
a Ignoring fish, poultry, and meat consumption, which differ by definition of the two groups, no other differences between the “vegetarians” and the “nonvegetarians” are statistically significant.
TABLE 3 MEAN
PLASMA
AND URINE
HORMONE
LEVELS
“Vegetarians” Plasma Day 11 E, (ng/dl) E, (ngidl) Prolactin (&ml) Day 22 E, (ng/dl) E2 h&-W Prolactin (t&ml) Progesterone (@ml) Progesterone 33.0 r&ml
6.3 6.0 23.1 9.2 13.2 25.4 3.2 50%
OF SEVENTH-DAY
ADVENTIST
“Nonvegetarians” 6.8 6.3 22.4 9.4 11.7 21.9 3.9 56%
TEENAGE
GIRLS
Total 6.6 6.2 22.7 9.3 12.4 23.4 3.6 53%
Urine Day 11 E, @g/l2 hr) E2 W12 h-1 Es 6.412 W ME, + Ed
2.08 1.24 2.68 0.79
2.15 1.22 2.83 0.84
2.12 1.23 2.76 0.81
Day 22 E, (&12 hr) E, WI2 hr) E, W12 hr) Ed@, + W
3.98 2.45 6.29 0.97
4.39 2.49 6.22 0.90
4.19 2.47 6.25 0.93
106
GRAY ET AL.
DISCUSSION
Contrary to expectations, the diets of the non-meat-eating Adventists, when expressed as proteins, fat, and carbohydrate, were very similar to those of their meat-eating schoolmates. No differences in height, weight, age at menarche, or hormone levels were found. More surprising still is the fact that they are very similar to other Southern Californian white girls of the same age (see under U.S. in Tables 1- 3 in companion paper, Ref. (7)). The Adventists had a slightly earlier age at menarche @DA vs U.S.: 12.5 vs 12.9 yr) and were very close in height (164.9 vs 165.1 cm) and weight (58.0 vs 59.7 kg). The frequency of meat consumption of the U.S. girls was about double that of the “nonvegetarian” Adventists, but fat provided only between 2 and 4% more of their calories (SDA vs U.S.: 36.0 and 38.3% vs 40.2%). The Day 11 plasma hormone levels were quite similar in the Adventists and other Southern Californian girls with mean plasma E, plus Ez values of 12.8 and 13.1 ng/dl, respectively, and plasma prolactin values of 22.7 and 23.3 rig/ml. Urine E, plus E, values were, however, 18% lower in the Adventist girls and their urinary estriol ratio [Ed(E, + EJ] was 31% higher-G.81 for Adventists vs 0.62 for other Southern Californian girls. A higher estriol ratio has been suggested as protecting against breast cancer (5, 12); however, the biological relevance of this ratio has been disputed (10, 19). In view of the fact that “vegetarian” and “nonvegetarian” Adventist teenagers are similar in terms of body size, age at menarche, and plasma hormone levels both to each other and to girls in the general population, one must seriously question the hypothesis that meat consumption is a risk factor for breast cancer. REFERENCES 1. Armstrong, B., and Doll, R. Environmental factors and cancer incidence and mortality in different countries, with special reference to dietary practices. Znr. J. Cancer 15, 617-631 (1975). 2. Bradley, C. J., Kledzik, G. S., and Meites, J. Prolactin and estrogen dependency of rat mammary cancers at early and late stages of development. Cancer Res. 36, 319-324 (1976). 3. Brown, J. B., MacNaughton, C., Smith, M. A., and Smyth, B. Further observations on the Kober colour and Ittrich fluorescence reactions in the measurement of estriol, oestrone, and oestradiol. J. Endocrinol. 40, 175-188 (1968). 4. Carrel, K. K., Gamma], E. B., and Plunkett, E. R. Dietary fat and mammary cancer. Canad. Med. Assoc. J. 98, SO-594 (1968). 5. Dickinson, L. E., MacMahon, B., Cole, P., and Brown, J. B. Estrogen profiles of Oriental and Caucasian women in Hawaii. New Engl. J. Med 291, 1211-1213 (1974). 6. Gray, G. E., Pike, M. C., and Henderson, B. E. Breast cancer incidence and mortality rates in different countries in relation to known risk factors and dietary practices. Brit. J. Cancer 39, 1-7 (1979). 7. Gray, G., Pike, M. C., Hirayama, T., Tellez, J., Gerkins, V., ef al. Diet and hormone profiles in teenage girls in four countries at different risk for breast cancer. Prev. Med. 11, 108- 113(1982). 8. Hirayama, T. Epidemiology of breast cancer with special reference to the role of diet. Prev. Med. 7, 173-195 (1978). 9. Kelsey, J. L. A review of the epidemiology of human breast cancer. Epidemiol. Rev. 1, 74- 109 (1979). 10. Lipsett, M. B. Oestrogen profiles and breast cancer. Lancet 2, 1378(1971). 11. MacMahon, B., Cole, P., and Brown, J. Etiology of human breast cancer: A review. .Z. Nat. Cancer Inst. 50, 21-42 (1973).
HORMONE LEVELS IN SEVENTH-DAY
ADVENTISTS
107
12. MacMahon, B., Cole, P., Brown, J. B., Aoki, K., Lin, T. M., et al. Urine oestrogen profiles of Asian and North American women. Int. J. Cancer 14, 161- 167 (1974). 13. Miller, A. B., and Bulbrook, R. D. The epidemiology and etiology of breast cancer. New Eng!. J. Med. 303, 1246-1248 (1980). 14. Moore, M. C. “Extended Table of Nutrient Values.” International Dietary Information Foundation, Atlanta, 1974. 15. Morgan, R. W., Jain, M., Miller, A. B., Choi, N. W., Matthews, V., et al. A comparison of dietary methods of epidemiologic studies. Amer. J. Epidemiol. 107, 488-498 (1978). 16. Nomura, A., Henderson, B. E., and Lee, J. Breast cancer and diet among the Japanese in Hawaii. Amer. J. Clin. Nutr. 31, 2020-2025 (1978). 17. Phillips, R. L., and Kuzma, J. W. Rationale and methods for an epidemiologic study of cancer among Seventh-Day Adventists. Nat. Cancer Inst. Monogr. 47, 107-112 (1977). 18. Welsch, C. W., and Meites, J. Prolactin and mammary carcinogenesis, in “Endocrine Control in Neoplasia” (R. Sharma and W. Criss, Eds.). Raven Press, New York, 1978. 19. Zumoff, B., Fishman, J., Bradlow, H. L., and Hellman, L. Hormone profiles in hormonedependent cancers. Cancer Res. 35, 3365-3373 (1975).
MEDICINE
11,
103-107 (1982)
SHORT REPORT Diet and Hormone
Levels in Seventh-Day Teenage Girls’
Adventist
GREGORYE. GRAY,* PHYLLIS WILLIAMS,? VEEBAGERKINS,* JAMESB. BROWN,+ BRUCEARMSTRONG,!? ROLANDPHILLIPS,? JOHN T. CASAGRANDE,*MALCOLM C.PIKE,* AND BRIAN E. HENDERSON*~~ *Department of Family and Preventive Medicine, University of Southern California, 2025 Zonal Avenue, Los Angeles, California 90033, tSchoo1 of Health, Loma Linda University, Loma Linda, California 92354, $Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria, Australia, and $Public Health Department, Perth, Western Australia, Australia
Seventh-Day Adventist women in California have a decreased mortality rate from breast cancer. If this lower rate is due to the fact that many Adventists are lactoovovegetarians (“vegetarians”) then one may find reduced levels of suggested risk factors for breast cancer in such Adventists. We studied this by comparing plasma and urine sex hormone levels in Seventh-Day Adventist “vegetatarian” and “nonvegetarian” girls aged 14 to 17. No differences were found between the two groups in Day 11 estrogens and prolactin, or in Day 22 estrogens, progesterone, and prolactin. Mean heights, weights, and ages at menarche were also similar. The Adventists were similar in height, weight, and age at menarche, and had similar plasma hormone levels, when compared with non-Adventist “control” girls.
INTRODUCTION
Mortality data show that the risk of dying from breast cancer for California Seventh-Day Adventist women is approximately 30% lower than that of the general California population (17). It has been suggested that this reduced rate may be due to their dietary habits (17), as many of them are lacto-ovovegetarians. This possibility is supported by international comparisons where it has been demonstrated that animal fat and meat consumption is highly correlated with breast cancer rates (1, 4, 6), and both case-control and cohort studies have suggested that meat consumption may be a risk factor for breast cancer (8, 16). Although an association has not been found in all studies, recent expert reviews have concluded that age at menarche is an important risk factor for breast cancer (9, 13). Risk to breast cancer in rodents is affected by hormone levels, in particular estrogens and prolactin (2, IS), and there is some evidence supporting this in humans (9, 11, 13). We therefore reasoned that, if meat consumption per se is a risk factor for breast cancer, one might find differences in age at menarche and in plasma and urine hormone levels between meat eating and non-meat-eating Adventists.
’ Supported by Grants POl-CA-17054 and CA-14089 from the National Cancer Institute. * To whom reprint requests should be addressed. 103 0091-7435/82/010103-05$02.00/O Copyright @ 1982 by Academic Press, Inc. All rights of reproduction in any form reserved.
104
GRAY
ET AL.
METHODS With the help of six Adventist academies in Southern California, we sought white girls aged 14-17 who had menstrual cycles between 27 and 32 days in length, had never used oral contraceptives, had never been pregnant, did not take medication regularly, had no prior history of gynecological, endocrine, or neoplastic diseases, and were willing to have blood and urine specimens taken for hormone analysis. We identified 23 girls who had never eaten meat on a regular basis (“vegetarians”) and 26 who were eating meat, fish, or poultry at least weekly (“nonvegetarians”). These girls completed a detailed questionnaire on dietary habits. The dietary questionnaire grouped foods into 88 categories and included information on frequency of consumption and serving size. The caloric, protein, carbohydrate, and fat intakes were estimated from this detailed food frequency questionnaire using food composition data from the Extended Table of Nutrient Values (14, 15). Blood samples were collected in the homes of the subjects between 30 min and 2 hr after arising on Days 11 and 22 of the same menstrual cycle. The blood was collected into lo-ml tubes containing potassium ethylenediaminetetraacetate (EDTA). After centrifugation, the plasma was separated and stored in several aliquots at -20°C. Plasma levels of progesterone, prolactin, estrone (E,), and estradiol (E,) were measured on coded samples by Endocrine Sciences Laboratory, Tarzana, California, by means of radioimmunoassay. Overnight urine specimens (12-hr) were also collected, the collections ending on the mornings when the blood samples were drawn. The urine was treated with 15 ml of 20% acetic acid, divided into 25ml aliquots, and stored at -20°C. Aliquots of urine were coded and air freighted frozen in dry ice to Melbourne where urine levels of El, Ez, and estriol (Es) were measured by one of us (J. B.) using a method involving spectrophotofluorimetry and internal radioactive standards (3). Urine hormone concentrations were converted into absolute amounts by multiplying the concentration by the total volume of urine collected. Tests of statistical significance were calculated using the standard t test.
TABLE 1 MEAN ANTHROPOMETRIC MEASUREMENTS AND AGE AT MENARCHE OF SEVENTH-DAY ADVENTIST TEENAGE GIRLS”
“Vegetarians” Height (cm) Weight (kg) Quetelet’s index* Menarche (years) N n None of the differences between significant. * (Weight/height”) x 10,000.
165.2 57.2 20.9 12.6 23 the “vegetarians”
“Nonvegetarians” 164.7 58.7 21.6 12.5 26 and the “nonvegetarians”
Total 164.9 58.0 21.3 12.5 49 are statistically
HORMONE LEVELS IN SEVENTH-DAY
105
ADVENTISTS
RESULTS
“Vegetarians” and “nonvegetarians” did not differ in height, weight, or age at menarche (Table 1). The relative amounts of protein, fat, and carbohydrates [expressed as percentage of calories] consumed by “vegetarians” and “nonvegetarians” were all very similar (Table 2). The mean hormone levels are shown in Table 3. The levels are quite similar and no statistically significant differences were found.
TABLE 2 MEAN
DIETARY
INTAKES
OF SEVENTH-DAY
ADVENTIST
GIRLS
“Nonvegetarians”
“Vegetarians” Protein (% of calories) Fat (% of calories) Carbohydrates (% of calories) Fish (servings per week) Poultry (servings per week) Meat (servings per week) Eggs (per week) Milk (servings per day) Other dairy products (servings per week)
TEENAGE
Total
17.6 36.0 46.4 0 0 0 2.6 2.6
17.2 38.3 44.5 1.1 1.3 2.5 3.1 2.4
17.4 37.2 45.4 0.7 0.8 1.5 2.9 2.5
7.1
7.4
7.3
a Ignoring fish, poultry, and meat consumption, which differ by definition of the two groups, no other differences between the “vegetarians” and the “nonvegetarians” are statistically significant.
TABLE 3 MEAN
PLASMA
AND URINE
HORMONE
LEVELS
“Vegetarians” Plasma Day 11 E, (ng/dl) E, (ngidl) Prolactin (&ml) Day 22 E, (ng/dl) E2 h&-W Prolactin (t&ml) Progesterone (@ml) Progesterone 33.0 r&ml
6.3 6.0 23.1 9.2 13.2 25.4 3.2 50%
OF SEVENTH-DAY
ADVENTIST
“Nonvegetarians” 6.8 6.3 22.4 9.4 11.7 21.9 3.9 56%
TEENAGE
GIRLS
Total 6.6 6.2 22.7 9.3 12.4 23.4 3.6 53%
Urine Day 11 E, @g/l2 hr) E2 W12 h-1 Es 6.412 W ME, + Ed
2.08 1.24 2.68 0.79
2.15 1.22 2.83 0.84
2.12 1.23 2.76 0.81
Day 22 E, (&12 hr) E, WI2 hr) E, W12 hr) Ed@, + W
3.98 2.45 6.29 0.97
4.39 2.49 6.22 0.90
4.19 2.47 6.25 0.93
106
GRAY ET AL.
DISCUSSION
Contrary to expectations, the diets of the non-meat-eating Adventists, when expressed as proteins, fat, and carbohydrate, were very similar to those of their meat-eating schoolmates. No differences in height, weight, age at menarche, or hormone levels were found. More surprising still is the fact that they are very similar to other Southern Californian white girls of the same age (see under U.S. in Tables 1- 3 in companion paper, Ref. (7)). The Adventists had a slightly earlier age at menarche @DA vs U.S.: 12.5 vs 12.9 yr) and were very close in height (164.9 vs 165.1 cm) and weight (58.0 vs 59.7 kg). The frequency of meat consumption of the U.S. girls was about double that of the “nonvegetarian” Adventists, but fat provided only between 2 and 4% more of their calories (SDA vs U.S.: 36.0 and 38.3% vs 40.2%). The Day 11 plasma hormone levels were quite similar in the Adventists and other Southern Californian girls with mean plasma E, plus Ez values of 12.8 and 13.1 ng/dl, respectively, and plasma prolactin values of 22.7 and 23.3 rig/ml. Urine E, plus E, values were, however, 18% lower in the Adventist girls and their urinary estriol ratio [Ed(E, + EJ] was 31% higher-G.81 for Adventists vs 0.62 for other Southern Californian girls. A higher estriol ratio has been suggested as protecting against breast cancer (5, 12); however, the biological relevance of this ratio has been disputed (10, 19). In view of the fact that “vegetarian” and “nonvegetarian” Adventist teenagers are similar in terms of body size, age at menarche, and plasma hormone levels both to each other and to girls in the general population, one must seriously question the hypothesis that meat consumption is a risk factor for breast cancer. REFERENCES 1. Armstrong, B., and Doll, R. Environmental factors and cancer incidence and mortality in different countries, with special reference to dietary practices. Znr. J. Cancer 15, 617-631 (1975). 2. Bradley, C. J., Kledzik, G. S., and Meites, J. Prolactin and estrogen dependency of rat mammary cancers at early and late stages of development. Cancer Res. 36, 319-324 (1976). 3. Brown, J. B., MacNaughton, C., Smith, M. A., and Smyth, B. Further observations on the Kober colour and Ittrich fluorescence reactions in the measurement of estriol, oestrone, and oestradiol. J. Endocrinol. 40, 175-188 (1968). 4. Carrel, K. K., Gamma], E. B., and Plunkett, E. R. Dietary fat and mammary cancer. Canad. Med. Assoc. J. 98, SO-594 (1968). 5. Dickinson, L. E., MacMahon, B., Cole, P., and Brown, J. B. Estrogen profiles of Oriental and Caucasian women in Hawaii. New Engl. J. Med 291, 1211-1213 (1974). 6. Gray, G. E., Pike, M. C., and Henderson, B. E. Breast cancer incidence and mortality rates in different countries in relation to known risk factors and dietary practices. Brit. J. Cancer 39, 1-7 (1979). 7. Gray, G., Pike, M. C., Hirayama, T., Tellez, J., Gerkins, V., ef al. Diet and hormone profiles in teenage girls in four countries at different risk for breast cancer. Prev. Med. 11, 108- 113(1982). 8. Hirayama, T. Epidemiology of breast cancer with special reference to the role of diet. Prev. Med. 7, 173-195 (1978). 9. Kelsey, J. L. A review of the epidemiology of human breast cancer. Epidemiol. Rev. 1, 74- 109 (1979). 10. Lipsett, M. B. Oestrogen profiles and breast cancer. Lancet 2, 1378(1971). 11. MacMahon, B., Cole, P., and Brown, J. Etiology of human breast cancer: A review. .Z. Nat. Cancer Inst. 50, 21-42 (1973).
HORMONE LEVELS IN SEVENTH-DAY
ADVENTISTS
107
12. MacMahon, B., Cole, P., Brown, J. B., Aoki, K., Lin, T. M., et al. Urine oestrogen profiles of Asian and North American women. Int. J. Cancer 14, 161- 167 (1974). 13. Miller, A. B., and Bulbrook, R. D. The epidemiology and etiology of breast cancer. New Eng!. J. Med. 303, 1246-1248 (1980). 14. Moore, M. C. “Extended Table of Nutrient Values.” International Dietary Information Foundation, Atlanta, 1974. 15. Morgan, R. W., Jain, M., Miller, A. B., Choi, N. W., Matthews, V., et al. A comparison of dietary methods of epidemiologic studies. Amer. J. Epidemiol. 107, 488-498 (1978). 16. Nomura, A., Henderson, B. E., and Lee, J. Breast cancer and diet among the Japanese in Hawaii. Amer. J. Clin. Nutr. 31, 2020-2025 (1978). 17. Phillips, R. L., and Kuzma, J. W. Rationale and methods for an epidemiologic study of cancer among Seventh-Day Adventists. Nat. Cancer Inst. Monogr. 47, 107-112 (1977). 18. Welsch, C. W., and Meites, J. Prolactin and mammary carcinogenesis, in “Endocrine Control in Neoplasia” (R. Sharma and W. Criss, Eds.). Raven Press, New York, 1978. 19. Zumoff, B., Fishman, J., Bradlow, H. L., and Hellman, L. Hormone profiles in hormonedependent cancers. Cancer Res. 35, 3365-3373 (1975).