€> 1991 S. Karger AG. Basel 0042-1138/91 /0462-0163$2.75/0
Urol Int 1991;46:163-166
Dietary Factors and Prostatic Cancer M.P. Bravo, E. Castellanos, J. del Rey Calero Department of Preventive Medicine, School of Medicine, Autonomous University of Madrid, Spain
Keywords. Prostatic cancer • Diet • Obesity • Meat • Fat • Vitamins Abstract. In order to learn about the influence of dietary factors and obesity on prostatic cancer in our environ ment, a case-control study was performed. The group of cases consisted of 90 men histologically diagnosed with prostatic cancer in the ‘La Paz’ hospital (Madrid) during the 4-year period of 1983-1987. The controls were 180 men selected to obtain a random sample of males from the same hospital, stratified according to age and date of admis sion as compared with the prostatic cancer patients. The results of the study revealed that a diet rich in animal fats as well as high in meat consumption increased the risk of prostatic cancer. Low ingestion of vitamin A or vitamin C and obesity were unassociated to the disease.
The relationships between dietary factors and pros tatic cancer have been investigated in several epidemio logical studies. Different authors found that the disease was directly associated to the abundance of fat and vita min A in the diet, although both associations were only observed in men over 70 years old [3, 9, 10]. Other authors reported an inverse association between the amounts of vitamins A and C in the diet and prostatic cancer [4, 14, 15]. Zinc and vitamin C do not seem to be related to the development of prostatic cancer, although Whelan et al. [20] reported lower serum Zn levels in prostatic cancer patients than in controls. Other studies have referred to a lower frequency of prostatic cancer among vegetarian men and men belonging to religious groups which prohibit meat consumption [17, 18]. The influence of obesity on prostatic cancer is contro versial because the association reported in some studies [ 11,16, 18] has not been found by other authors [5,10,22], The present report describes a case-control study per formed to learn about the possible association between obesity or dietary factors and prostatic cancer in our environment.
Patients The cases were 90 men histologically diagnosed with prostatic carcinoma in the ‘La Paz’ Hospital (Madrid) from January 1983 to December 1987. The patients' age ranged from 50 to 88 years. The controls were 180 patients with diseases other than urologic diseases or a primary tumor. They were selected among the patients of the following hospital sections: traumatology (53 patients); gastroenter ology (26 patients); respiratory diseases (19 patients); general sur gery (42 patients); dermatology (27 patients); and neurology (13). The controls were selected to obtain a random sample of males from the same hospital stratified according to age (six age groups: 55-59; 60-64; 65-69; 70-74; 75-79; and > 80 years of age) and date (year and month) of hospital admission as compared with the prostatic cancer patients. The data for the study were obtained from the clinical histories of the hospital archives as well as from a standarized questionnaire which was personally administered to all patients (prostatic cancer patients and controls) by two interviewers trained for the study. The questions covered the study of occupational, medical, social, demo graphic and dietary factors including the types and amounts of foods consumed. The diets were classified into 5 types: normal, rich in animal fats, rich in vegetable fats, deficient in vitamin A, and defi cient in vitamin C. For this classification, the WHO and FAO stan dards for nutritional adequacy of the diet [7, 21] were used. The composition of foods ingested was evaluated using the data pro vided by the ‘Institute for Nutrition’ (Madrid) [8]. Obesity was mea sured by the body mass index. The associations between the dietary factors studied or obesity and prostatic cancer were analyzed by
Downloaded by: King's College London 137.73.144.138 - 1/11/2019 1:06:16 AM
Introduction
Bravo/Castellanos/del Rey Calero
164
Table 1. Relation between diet types and prostatic cancer P
Diet type limits
Normal Rich in animal fats
2 Xmh
C
60 28
126 23
Rich in vegetable fats 15 Vitamin A deficient 7
25 10
Vitamin C deficient
14
8
8.75 p = 0.03 0.41 0.56 p - 0.45 0.15
Odds ratio
Confidence
2.56
1.30-5.05
1.26 1.47
0.58-2.71 0.48-4.46
Low fat content Beef and/or chicken 54 High fa t content 17 Lamb
1.20
0.43-3.26
Pork
Type of meat
P = Prostatic cancer patients; C - controls. Some of the patients are included in more than one group.
Table 2. Relation between meat consumption and prostatic cancer Units/week
P
C
< 1 2-4
28 30
93 40
>5
32
47
Table 3. Relation between type of meat consumed and prostatic cancer
Xmh
Odds ratio
Confidence limits
8.11 p - 0.004 6.83 p = 0.008
2.49
1.26-4.94
2.26
1.17-4.39
1 unit = 160 g; P = prostatic cancer patients; C = controls.
calculating the odds ratios. The statistical significance of the results was evaluated with the Mantel-Haenszel’s test [12], The analysis was conducted by using the Epi-Info program [2],
P
19
C
Xmh
° dds ratio
Confidence limits
129 20 31
3.79 2.03 p = 0.051 1.31 1.46 p = 0.520
0.93-4.43 0.72-2.95
P = Prostatic cancer patients; C = controls.
stratified according to the amount of meat consumed weekly. When meat was a regular part of the diet (from 2 units/week onwards), there was a significant association to the disease. The risk of prostatic cancer did not increase with the quantity of meat consumed. The study of the types of meat consumed is shown in table 3. No association between consumption of beef or chicken (meats with low fat content) and prostatic cancer was found. However, the percentages of men consuming either lamb or pork (meats with high fat content) were higher in the prostatic cancer patient group than in the control group, with significantly increased risk in the group of lamb consumers. The disease did not seem to be associated to obesity (table 4), even in the prostatic cancer patients with many years of excess weight (table 5).
Discussion
The results of the epidemiological study of the types of diet in the prostatic cancer patients and their controls are shown in table 1. The percentages of prostatic cancer patients and their controls with a normal diet were sim ilar (66.6% and 70%, respectively). The risk of prostatic cancer was increased in men with a diet rich in animal fats. The other diet types analyzed (diets rich in vegeta ble fats, vitamin A deficiency, and vitamin C deficiency) did not turn out to be associated to prostatic cancer (table 1). The relationships between prostatic cancer and meat consumption are expressed in table 2. The patients were
The results of this study show that there is an associa tion between several dietary factors and prostatic cancer in our environment. The association of the disease to a fat-rich diet stated in some reports [10, 18] is also found in our patient sample. The separate study of vegetable and animal fats in our investigation demonstrated in creased risk only for animal fats. The noxious effects of these fats on the prostate gland have been attributed to the accumulation of cholesterol epoxides in the prostatic tissue where they exert a carcinogenic effect [10]. Another explanation would be that the abundant fat ingested would stimulate bile salt excretion, thereby pos sibly altering the normal intestinal flora and thus in-
Downloaded by: King's College London 137.73.144.138 - 1/11/2019 1:06:16 AM
Results
165
Dietary Factors and Prostatic Cancer
Table 4. Relation between antecedents of obesity and prostatic cancer Controls
Patients
Antecedents of obesity
n Absent Present
66 24
Total
90
%
64.45 35.55 100
100
Confidence limits
0.66
0.36-1.19
n
%
73.3 26.7
Odds ratio
116 64 180
X2 = 2.15 (nonsignificant).
Table 5. Relation between years of excess weight and prostatic cancer Excess weight, years
Patients
Controls
n
%
%
n
0 10-24 25-39 >40
66 7 9 8
73.3 7.8 10 8.9
64.45 20.55 7.22 7.78
116 37 13 14
Total
90
100
100
Odds ratio
Confidence limits
Xmh
0.33 0.67 1
0.13-0.83 0.45-3.25 0.36-2.73
6.68 0.18 0
180
creasing the carcinogenic factors produced by these mi croorganisms. These factors might then reach the pros tate gland and promote its malignant transformation. In our study, an association between a diet deficient in vitamins A or C was not found. However, the number of patients with such deficiencies was low because the diet of the Spanish population - like that of other Med iterranean countries - usually contains abundant fruits and vegetables. The association between prostatic cancer and low ingestion of vitamins A and C has been pro posed by several authors [4, 15, 17] who suggested that these vitamins may inhibit the carcinogenic effects of some agents. It has been reported that, in men with pros tatic carcinoma, serum levels of (3-carotene and a-tocopherol varies with the developmental stage of the disease and the diet type, whereas the mean level of serum reti nol was significantly lower in prostatic cancer patients than in the controls [4], It has also been shown that reti noids can inhibit metaplastic changes induced by both chemical carcinogens and testosterone [13]. However, other authors have reported that the disease is positively
associated to a high intake of vitamins A and C [4, 6, 10], The enhancement of carcinogenesis by vitamin A has been attributed to (a) the influence of this vitamin on the synthesis of testosterone, which seems to play a role in the development of prostatic cancer [ 10, 13]; (b) vita min A has metabolic interactions with zinc which may be a risk factor for prostatic cancer [20]; and (c) this vitamin may enhance the proliferation of prostatic epi thelial cells, thereby stimulating the progression of occult tumor foci [9]. In our study, meat consumption was positively asso ciated to the development of prostatic cancer. This asso ciation has also been observed in other studies [1,4] and might be related to the high fat content of meat-rich diets, but also to the use of estrogens in the feeding of animals fattened for human consumption [19], An association between prostatic cancer and in creased body weight has been reported [11, 16, 18], Our results and those of other authors [5, 10, 22] suggest that obesity is not a risk factor for prostatic cancer. Obesity is not only due to an increased fat consumption; it may
Downloaded by: King's College London 137.73.144.138 - 1/11/2019 1:06:16 AM
X2 = 7.37 (nonsignificant).
Bravo/Castellanos/del Rey Calero
also result from an energetic imbalance that can be caused by factors other than diet composition. In addi tion, the increase in adipose tissue in obese men can pro mote the transformation of androstenodione into estro gens which might act as a protective factor against the development of prostatic cancer. References 1 Benson, M.C.; Kaplan, S.A.; Olsson, C.A.: Prostate cancer in men less than 45 years old; influence of stage, grade and therapy. J. Urol. 137: 888-890 (1987). 2 Dean, J.A.; Dean, A.G.; Burton, A.; Dicker, R.: Epi-Info. Divi sion of surveillance and epidemiologic studies. Epidemiology program office (Centers for Disease Control, Atlanta 1987). 3 Graham, S.; Haughey, B.; Marshall, J.: Diet in the epidemiology of carcinoma of the prostate gland. J. natn. Cancer Inst. 70:687692 (1983). 4 Hayes, R.B.; Boganovicz, J.F.A.T.; Schroeder, F.H.; De Bruijn, A.; Raatgever, J.W.; van der Mass, P.J.; Oishi, K.; Yoshida, O.: Serum retinol and prostate cancer. Cancer 62: 2021-2026 (1988). 5 Honda, G.D.; Bernstein, L.; Ross, R.K.; Greenland, S.: Vasecto my, cigarette smoking, and age at first sexual intercourse as risk factors for prostate cancer in middle-aged men. Br. J. Cancer 57: 326-331 (1988). 6 Hirayama, T.: A cohort study on cancer in Japan; in United States-Japan Cooperative Research Program: Statistical meth ods in cancer epidemiology, pp. 73-91 (The Radiation Effects Research Foundation, Hiroshima 1985). 7 Instituto de Nutrición: Ingestas recomendadas de energía y nutrientes para la población española (Consejo Superior de Investigaciones Científicas, Madrid 1981). 8 Instituto de Nutrición: Tablas de composición de alimentos (Consejo Superior de Investigaciones Científicas, Madrid 1983). 9 Kolonel, L.N.; Nankin, J.H.; Yoshizawa, C.N.: Vitamin A and prostate cancer in elderly men: enhancement of risk. Cancer Res. 47: 2982-2985 (1987). 10 Kolonel, L.N.; Yoshizawa, C.N.; Nankin, J.H.: Diet and pros tatic cancer: a case-control study in Hawaii. Am. J. Epidem. 127: 999-1012 (1988). 11 Kew, E.A.; Garfinkel, L.: Variations in mortality by weight among 750,000 men and women. J. chron. Dis. 32: 563-576 (1979).
12 Mantel, N.; Haenszel, W.: Statistical aspects of analysis of data from retrospective studies of disease. J. natn. Cancer Inst. 22: 719-726 (1959). 13 Müller Salami, L.; Matter, A.; Lasnitzki, I.: Interaction of reti noic acid and 3-methylcholanthrene on the fine structure of mouse prostate epithelium in vitro. J. natn. Cancer Inst. 63: 485-595 (1979). 14 Ross, R.K.; Paganini-Hill, A.; Henderson, B.E.: The etiology of prostate cancer: what does the epidemiology suggest? Prostate 4: 333-344(1983). 15 Silverberg, E.: Statistical and epidemiologic data on urologic cancer. Cancer 60: 692-717 (1987). 16 Severson, R.K.; Grove, J.S.; Nomura, A.M.Y.; Stemmermann, G.N.: Body mass and prostatic cancer: a prospective study. Br. Med. J. 297: 713-715 (1988). 17 Schuman, L.M.; Mandel, J.S.; Radke, A.; Seal, U.; Halbcrg, F.: Some selected features of the epidemiology of prostate cancer: Minneapolis-St. Paul, Minnesota case-control study, 1976— 1979; in Magnus, Trends in cancer incidence: causes and practi cal implications, pp. 345-354 (Hemisphere Publishing, Wash ington 1982). 18 Snowdon, D.A.; Philips, R.L.; Choi, W.: Diet, obesity, and risk of fatal prostate cancer. Am. J. Epidem. 120: 244-250 (1984). 19 Terasaki, P.I.; Perdue, S.T.; Ickey, M.R.: HLA frequencies in cancer; a second study; in progress in cancer research and thera py, vol. 3: Genetics of human cancer, pp. 321-328 (Raven Press, New York 1977). 20 Whelan, P.; Walker, B.E.; Kelleher, J.: Zinc, vitamin A and pros tatic cancer. Br. J. Urol. 55: 525-528 (1983). 21 Wretlind, A.: Standards for nutritional adequacy of the diet. European and WHO/FAO viewpoints. Am. J. clin. Nutr. 36: 366-371 (1982). 22 Wynder, E.L.; Mabuchi, K.; Whitmore, W.F.: Epidemiology of cancer of the prostate. Cancer 28: 344-355 (1971).
Received: November 3, 1989 Accepted after revision: April 11,1990 Dr. Maria Pilar Bravo Department of Preventive Medicine School of Medicine Autonomous University Cl Arzobispo Morcillo 2 E-28029 Madrid (Spain)
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166
Urol Int 1991;46:163-166
Dietary Factors and Prostatic Cancer M.P. Bravo, E. Castellanos, J. del Rey Calero Department of Preventive Medicine, School of Medicine, Autonomous University of Madrid, Spain
Keywords. Prostatic cancer • Diet • Obesity • Meat • Fat • Vitamins Abstract. In order to learn about the influence of dietary factors and obesity on prostatic cancer in our environ ment, a case-control study was performed. The group of cases consisted of 90 men histologically diagnosed with prostatic cancer in the ‘La Paz’ hospital (Madrid) during the 4-year period of 1983-1987. The controls were 180 men selected to obtain a random sample of males from the same hospital, stratified according to age and date of admis sion as compared with the prostatic cancer patients. The results of the study revealed that a diet rich in animal fats as well as high in meat consumption increased the risk of prostatic cancer. Low ingestion of vitamin A or vitamin C and obesity were unassociated to the disease.
The relationships between dietary factors and pros tatic cancer have been investigated in several epidemio logical studies. Different authors found that the disease was directly associated to the abundance of fat and vita min A in the diet, although both associations were only observed in men over 70 years old [3, 9, 10]. Other authors reported an inverse association between the amounts of vitamins A and C in the diet and prostatic cancer [4, 14, 15]. Zinc and vitamin C do not seem to be related to the development of prostatic cancer, although Whelan et al. [20] reported lower serum Zn levels in prostatic cancer patients than in controls. Other studies have referred to a lower frequency of prostatic cancer among vegetarian men and men belonging to religious groups which prohibit meat consumption [17, 18]. The influence of obesity on prostatic cancer is contro versial because the association reported in some studies [ 11,16, 18] has not been found by other authors [5,10,22], The present report describes a case-control study per formed to learn about the possible association between obesity or dietary factors and prostatic cancer in our environment.
Patients The cases were 90 men histologically diagnosed with prostatic carcinoma in the ‘La Paz’ Hospital (Madrid) from January 1983 to December 1987. The patients' age ranged from 50 to 88 years. The controls were 180 patients with diseases other than urologic diseases or a primary tumor. They were selected among the patients of the following hospital sections: traumatology (53 patients); gastroenter ology (26 patients); respiratory diseases (19 patients); general sur gery (42 patients); dermatology (27 patients); and neurology (13). The controls were selected to obtain a random sample of males from the same hospital stratified according to age (six age groups: 55-59; 60-64; 65-69; 70-74; 75-79; and > 80 years of age) and date (year and month) of hospital admission as compared with the prostatic cancer patients. The data for the study were obtained from the clinical histories of the hospital archives as well as from a standarized questionnaire which was personally administered to all patients (prostatic cancer patients and controls) by two interviewers trained for the study. The questions covered the study of occupational, medical, social, demo graphic and dietary factors including the types and amounts of foods consumed. The diets were classified into 5 types: normal, rich in animal fats, rich in vegetable fats, deficient in vitamin A, and defi cient in vitamin C. For this classification, the WHO and FAO stan dards for nutritional adequacy of the diet [7, 21] were used. The composition of foods ingested was evaluated using the data pro vided by the ‘Institute for Nutrition’ (Madrid) [8]. Obesity was mea sured by the body mass index. The associations between the dietary factors studied or obesity and prostatic cancer were analyzed by
Downloaded by: King's College London 137.73.144.138 - 1/11/2019 1:06:16 AM
Introduction
Bravo/Castellanos/del Rey Calero
164
Table 1. Relation between diet types and prostatic cancer P
Diet type limits
Normal Rich in animal fats
2 Xmh
C
60 28
126 23
Rich in vegetable fats 15 Vitamin A deficient 7
25 10
Vitamin C deficient
14
8
8.75 p = 0.03 0.41 0.56 p - 0.45 0.15
Odds ratio
Confidence
2.56
1.30-5.05
1.26 1.47
0.58-2.71 0.48-4.46
Low fat content Beef and/or chicken 54 High fa t content 17 Lamb
1.20
0.43-3.26
Pork
Type of meat
P = Prostatic cancer patients; C - controls. Some of the patients are included in more than one group.
Table 2. Relation between meat consumption and prostatic cancer Units/week
P
C
< 1 2-4
28 30
93 40
>5
32
47
Table 3. Relation between type of meat consumed and prostatic cancer
Xmh
Odds ratio
Confidence limits
8.11 p - 0.004 6.83 p = 0.008
2.49
1.26-4.94
2.26
1.17-4.39
1 unit = 160 g; P = prostatic cancer patients; C = controls.
calculating the odds ratios. The statistical significance of the results was evaluated with the Mantel-Haenszel’s test [12], The analysis was conducted by using the Epi-Info program [2],
P
19
C
Xmh
° dds ratio
Confidence limits
129 20 31
3.79 2.03 p = 0.051 1.31 1.46 p = 0.520
0.93-4.43 0.72-2.95
P = Prostatic cancer patients; C = controls.
stratified according to the amount of meat consumed weekly. When meat was a regular part of the diet (from 2 units/week onwards), there was a significant association to the disease. The risk of prostatic cancer did not increase with the quantity of meat consumed. The study of the types of meat consumed is shown in table 3. No association between consumption of beef or chicken (meats with low fat content) and prostatic cancer was found. However, the percentages of men consuming either lamb or pork (meats with high fat content) were higher in the prostatic cancer patient group than in the control group, with significantly increased risk in the group of lamb consumers. The disease did not seem to be associated to obesity (table 4), even in the prostatic cancer patients with many years of excess weight (table 5).
Discussion
The results of the epidemiological study of the types of diet in the prostatic cancer patients and their controls are shown in table 1. The percentages of prostatic cancer patients and their controls with a normal diet were sim ilar (66.6% and 70%, respectively). The risk of prostatic cancer was increased in men with a diet rich in animal fats. The other diet types analyzed (diets rich in vegeta ble fats, vitamin A deficiency, and vitamin C deficiency) did not turn out to be associated to prostatic cancer (table 1). The relationships between prostatic cancer and meat consumption are expressed in table 2. The patients were
The results of this study show that there is an associa tion between several dietary factors and prostatic cancer in our environment. The association of the disease to a fat-rich diet stated in some reports [10, 18] is also found in our patient sample. The separate study of vegetable and animal fats in our investigation demonstrated in creased risk only for animal fats. The noxious effects of these fats on the prostate gland have been attributed to the accumulation of cholesterol epoxides in the prostatic tissue where they exert a carcinogenic effect [10]. Another explanation would be that the abundant fat ingested would stimulate bile salt excretion, thereby pos sibly altering the normal intestinal flora and thus in-
Downloaded by: King's College London 137.73.144.138 - 1/11/2019 1:06:16 AM
Results
165
Dietary Factors and Prostatic Cancer
Table 4. Relation between antecedents of obesity and prostatic cancer Controls
Patients
Antecedents of obesity
n Absent Present
66 24
Total
90
%
64.45 35.55 100
100
Confidence limits
0.66
0.36-1.19
n
%
73.3 26.7
Odds ratio
116 64 180
X2 = 2.15 (nonsignificant).
Table 5. Relation between years of excess weight and prostatic cancer Excess weight, years
Patients
Controls
n
%
%
n
0 10-24 25-39 >40
66 7 9 8
73.3 7.8 10 8.9
64.45 20.55 7.22 7.78
116 37 13 14
Total
90
100
100
Odds ratio
Confidence limits
Xmh
0.33 0.67 1
0.13-0.83 0.45-3.25 0.36-2.73
6.68 0.18 0
180
creasing the carcinogenic factors produced by these mi croorganisms. These factors might then reach the pros tate gland and promote its malignant transformation. In our study, an association between a diet deficient in vitamins A or C was not found. However, the number of patients with such deficiencies was low because the diet of the Spanish population - like that of other Med iterranean countries - usually contains abundant fruits and vegetables. The association between prostatic cancer and low ingestion of vitamins A and C has been pro posed by several authors [4, 15, 17] who suggested that these vitamins may inhibit the carcinogenic effects of some agents. It has been reported that, in men with pros tatic carcinoma, serum levels of (3-carotene and a-tocopherol varies with the developmental stage of the disease and the diet type, whereas the mean level of serum reti nol was significantly lower in prostatic cancer patients than in the controls [4], It has also been shown that reti noids can inhibit metaplastic changes induced by both chemical carcinogens and testosterone [13]. However, other authors have reported that the disease is positively
associated to a high intake of vitamins A and C [4, 6, 10], The enhancement of carcinogenesis by vitamin A has been attributed to (a) the influence of this vitamin on the synthesis of testosterone, which seems to play a role in the development of prostatic cancer [ 10, 13]; (b) vita min A has metabolic interactions with zinc which may be a risk factor for prostatic cancer [20]; and (c) this vitamin may enhance the proliferation of prostatic epi thelial cells, thereby stimulating the progression of occult tumor foci [9]. In our study, meat consumption was positively asso ciated to the development of prostatic cancer. This asso ciation has also been observed in other studies [1,4] and might be related to the high fat content of meat-rich diets, but also to the use of estrogens in the feeding of animals fattened for human consumption [19], An association between prostatic cancer and in creased body weight has been reported [11, 16, 18], Our results and those of other authors [5, 10, 22] suggest that obesity is not a risk factor for prostatic cancer. Obesity is not only due to an increased fat consumption; it may
Downloaded by: King's College London 137.73.144.138 - 1/11/2019 1:06:16 AM
X2 = 7.37 (nonsignificant).
Bravo/Castellanos/del Rey Calero
also result from an energetic imbalance that can be caused by factors other than diet composition. In addi tion, the increase in adipose tissue in obese men can pro mote the transformation of androstenodione into estro gens which might act as a protective factor against the development of prostatic cancer. References 1 Benson, M.C.; Kaplan, S.A.; Olsson, C.A.: Prostate cancer in men less than 45 years old; influence of stage, grade and therapy. J. Urol. 137: 888-890 (1987). 2 Dean, J.A.; Dean, A.G.; Burton, A.; Dicker, R.: Epi-Info. Divi sion of surveillance and epidemiologic studies. Epidemiology program office (Centers for Disease Control, Atlanta 1987). 3 Graham, S.; Haughey, B.; Marshall, J.: Diet in the epidemiology of carcinoma of the prostate gland. J. natn. Cancer Inst. 70:687692 (1983). 4 Hayes, R.B.; Boganovicz, J.F.A.T.; Schroeder, F.H.; De Bruijn, A.; Raatgever, J.W.; van der Mass, P.J.; Oishi, K.; Yoshida, O.: Serum retinol and prostate cancer. Cancer 62: 2021-2026 (1988). 5 Honda, G.D.; Bernstein, L.; Ross, R.K.; Greenland, S.: Vasecto my, cigarette smoking, and age at first sexual intercourse as risk factors for prostate cancer in middle-aged men. Br. J. Cancer 57: 326-331 (1988). 6 Hirayama, T.: A cohort study on cancer in Japan; in United States-Japan Cooperative Research Program: Statistical meth ods in cancer epidemiology, pp. 73-91 (The Radiation Effects Research Foundation, Hiroshima 1985). 7 Instituto de Nutrición: Ingestas recomendadas de energía y nutrientes para la población española (Consejo Superior de Investigaciones Científicas, Madrid 1981). 8 Instituto de Nutrición: Tablas de composición de alimentos (Consejo Superior de Investigaciones Científicas, Madrid 1983). 9 Kolonel, L.N.; Nankin, J.H.; Yoshizawa, C.N.: Vitamin A and prostate cancer in elderly men: enhancement of risk. Cancer Res. 47: 2982-2985 (1987). 10 Kolonel, L.N.; Yoshizawa, C.N.; Nankin, J.H.: Diet and pros tatic cancer: a case-control study in Hawaii. Am. J. Epidem. 127: 999-1012 (1988). 11 Kew, E.A.; Garfinkel, L.: Variations in mortality by weight among 750,000 men and women. J. chron. Dis. 32: 563-576 (1979).
12 Mantel, N.; Haenszel, W.: Statistical aspects of analysis of data from retrospective studies of disease. J. natn. Cancer Inst. 22: 719-726 (1959). 13 Müller Salami, L.; Matter, A.; Lasnitzki, I.: Interaction of reti noic acid and 3-methylcholanthrene on the fine structure of mouse prostate epithelium in vitro. J. natn. Cancer Inst. 63: 485-595 (1979). 14 Ross, R.K.; Paganini-Hill, A.; Henderson, B.E.: The etiology of prostate cancer: what does the epidemiology suggest? Prostate 4: 333-344(1983). 15 Silverberg, E.: Statistical and epidemiologic data on urologic cancer. Cancer 60: 692-717 (1987). 16 Severson, R.K.; Grove, J.S.; Nomura, A.M.Y.; Stemmermann, G.N.: Body mass and prostatic cancer: a prospective study. Br. Med. J. 297: 713-715 (1988). 17 Schuman, L.M.; Mandel, J.S.; Radke, A.; Seal, U.; Halbcrg, F.: Some selected features of the epidemiology of prostate cancer: Minneapolis-St. Paul, Minnesota case-control study, 1976— 1979; in Magnus, Trends in cancer incidence: causes and practi cal implications, pp. 345-354 (Hemisphere Publishing, Wash ington 1982). 18 Snowdon, D.A.; Philips, R.L.; Choi, W.: Diet, obesity, and risk of fatal prostate cancer. Am. J. Epidem. 120: 244-250 (1984). 19 Terasaki, P.I.; Perdue, S.T.; Ickey, M.R.: HLA frequencies in cancer; a second study; in progress in cancer research and thera py, vol. 3: Genetics of human cancer, pp. 321-328 (Raven Press, New York 1977). 20 Whelan, P.; Walker, B.E.; Kelleher, J.: Zinc, vitamin A and pros tatic cancer. Br. J. Urol. 55: 525-528 (1983). 21 Wretlind, A.: Standards for nutritional adequacy of the diet. European and WHO/FAO viewpoints. Am. J. clin. Nutr. 36: 366-371 (1982). 22 Wynder, E.L.; Mabuchi, K.; Whitmore, W.F.: Epidemiology of cancer of the prostate. Cancer 28: 344-355 (1971).
Received: November 3, 1989 Accepted after revision: April 11,1990 Dr. Maria Pilar Bravo Department of Preventive Medicine School of Medicine Autonomous University Cl Arzobispo Morcillo 2 E-28029 Madrid (Spain)
Downloaded by: King's College London 137.73.144.138 - 1/11/2019 1:06:16 AM
166
