Int. J . Cancer: 46, 12-15 (1990) 0 1990 Wiley-Liss, Inc.
Publication of the International Union Against Cancer Publication de I'Union lnternationale Contre 1e Cancer
FREQUENCY OF MEAT AND FISH INTAKE AND RISK OF BREAST CANCER IN A PROSPECTIVE STUDY OF 14,500 NORWEGIAN WOMEN Lars J. VATTEN'.2,4,5,Kari sOLVOLL3 and Elin B. L6KEN3 'Department of Oncology, University Hospital, N-7006 Trondheim; 2The Norwegian Cancer Registry, Montebello, N-0310 Oslo 3; and 'Sectionfor Dietary Research, Institute of Nutrition Research, University of Oslo, N-0317 Oslo 3, Norway. The association between the frequency of meat and fish intake and the incidence rate of breast cancer has been analyzed in 152 incident cases that developed among 14,500 Norwegian women during I I to 14 years of follow-up. A t the time of dietary inquiry they were between 35 and 51 years of age. A positive association was observed between the frequency of overall meat intake and breast cancer risk. There was an age-adjusted incidence rate ratio (IRR) of 1.8 (95% confidence limits, 1.1 and 3.1) for women who had a main meal with meat 5 times or more per week compared to women who had 2 meat dinners or less per week, and this associationdisplayed a linear trend (x' trend = 4.30, p = 0.04). No association was detected between the overall frequency of fish for dinner and breast cancer risk (x' trend = 1.39, p = 0.24), but there was an inverse relation with the frequency of main meals containing fish in poached form. The age-adjusted IRR was 0.7 (95% confidence limits, 0.4 and 1.0) for women who had poached fish for dinner at least 5 times per month compared to women who had fish in this form twice monthly or less often trend = 3.56, p = 0.06). The positive association with meat may be in accordance with the hypothesis that dietary fat increases the risk of breast cancer. Although there was no association with overall fish intake, the inverse relation with poached fish might deserve further investigation.
(x'
Dietary studies of breast cancer have typically focused on the hypothesis that there is a positive association between consumption of fat and breast cancer risk (Rohan and Bain, 1987). The strong correlation between per capita fat consumption and national incidence rates of breast cancer yields ecological evidence for a positive association with dietary fat (Armstrong and Doll, 1975; Waterhouse et al., 1982). Animal experiments have supported this association, showing that both type and amount of fat intake may influence incidence and growth of mammary tumours (Tannenbaum and Silverstone, 1953; Wynder et a l . , 1986). Prospective epidemiological studies (Willett et al., 1987; Jones et al., 1987), however, have failed to replicate any positive association based on individual information of dietary intake. The hypothesis that dietary fish intake is negatively associated with the risk of breast cancer has not been confirmed in human studies based on individual dietary information. One correlation study found a negative association between fish consumption and incidence and mortality rates of breast cancer between different countries (Kaizer et al., 1989). The international variation shows that, in certain countries where fish intake is high (e.g. Japan), the incidence rate of breast cancer is comparatively low. Since animal experiments have suggested that fish oils (omega-3 fatty acids) both protect against the occurrence and slow down the growth of mammary carcinomas in rodents (Kannali et al., 1984), it is important to examine the relation between dietary fish intake and breast cancer risk in humans. In this prospective study of 14,500 Norwegian women, we have examined the relation between the frequency of overall meat and fish consumption and the subsequent risk of developing breast cancer during a mean follow-up time of 12 years.
49 years living in 3 separate counties in Norway were invited to participate in a health screening examination organized by the National Health Screening Service (Bjartveit et al., 1979, 1983). Its main objective was to collect information on known and suspected risk factors for cardiovascular disease and hence, no information on factors usually associated with breast cancer risk, such as age at menarche, age at first birth, or exact age at menopause, was collected. A total of 24,617 women (93.8%) attended the screening, and every participant in one county and subsamples from the 2 other counties received a dietary questionnaire, which was filled in and returned by 14,729 women (95%). The official 11-digit person number of Norwegian subjects facilitated linkage to the Cancer Registry in order to identify 152 incident cases of breast cancer that had been diagnosed and reported during 11 to 14 years of follow-up. To reduce a potential bias due to preclinical changes in dietary habits, 171 cancer cases (including breast cancer) that had occurred prior to or during the calendar year of examination were excluded. Fifty-eight questionnaires were excluded for technical reasons, thus giving a total of 14,500 women eligible for analysis. About 60 food frequency questions covered a limited number of food items, which have been described elsewhere (Solvoll et d.,1989). Since the entire diet was not included, computation of energy or specific nutrient intake was not possible. The reproducibility of the dietary questionnaire has been tested among a group of women who completed the questionnaire on two occasions with an interval of 1 month (L@kenand Solvoll, 1987). Information from the questionnaire has also been compared to data from a 24-hr dietary recall among a subsample of the study participants (Solvoll, 1983). In general, it was concluded that the food frequency questionnaire produced fairly reliable information on intake of food items that were consumed on a regular, daily basis (e.g., milk, bread, coffee). The quality of the information related to main meal dishes (e.g. fish, meat) and food items of which consumption is typically less frequent and more irregular, however, could not be appropriately validated by the 24-hr recall method. For each person belonging to a certain category of food intake, observation years at risk of developing breast cancer were computed as the number of years accumulated from the screening examination until withdrawal in the year of diagnosis, at death from another cause, or at the end of follow-up, to allow comparison of person-time-based incidence rates of breast cancer for different categories of each food item. Incidence rate ratios (IRR) were computed as the rate in a specific food frequency category divided by the estimated rate
41n collaboration with The National Health Screening Service, P.O. Box 8155 Dep., Oslo 1, Norway.
5To whom reprint requests should be sent, at the Department of Oncology, University Hospital, N-7G06 Trondheim, Norway.
SUBJECTS AND METHODS
Between 1974 and 1977, all the men and women aged 35 to
Received: February 5 , 1990.
13
COHORT STUDY ON DIET A N D BREAST CANCER
meal and risk of breast cancer. Nonetheless, there was a 30% reduction in breast cancer risk associated with having fish in poached form as part of one's main meal 5 times or more per month compared to having poached fish no more than 1 or 2 times a month. The inverse relation with poached fish was not statistically significant, but the positive association with overall meat intake appears less likely to be due to chance. However, in view of the many food items tested, it cannot be excluded that a RESULTS statistically significant finding may appear as a chance result Table I shows that there was a positive association between due to multiple comparisons. the overall intake of dinners made from meat and breast cancer Since meat is one of the important sources of fat in the risk. Women who had meat dinners 5 times or more per week had an age-adjusted IRR of 1.8 (95% C.L., 1 . 1 and 3.1) com- Norwegian diet, the observed positive association between the pared to women who had 2 or less meat dinners per week. The frequency of overall meat consumption and breast cancer risk test for linear trend associated with overall meat intake (3 may reflect an effect of dietary fat, which has been widely categories) was statistically significant (x2 for trend = 4.30, studied in humans (Rohan and Bain, 1987). Correlation studies p = 0.04). Further adjustment for body mass index did not between countries support this result, showing a strong association between per capita fat consumption and national incimaterially alter the estimates of effect. dence rates of breast cancer (Armstrong and Doll, 1975). FurThere was no association between the frequency of overall ther support for the association with dietary fat can be derived fish intake and risk of breast cancer (Table 11). Women who from animal experiments (Wynder et al., 1986). Case-control reported having fish as part of their main meal more often than studies have yielded results in both directions (Lubin et al., twice a week had an incidence rate ratio (IRR) of 1.2 (95%CL, 1981; Grahametal., 1982; Talamani etal., 1984; Lubinetal., 0.8 and 1.7) compared to women whose overall fish consump- 1986; Katsouyanni et al., 1986; Toniolo et al., 1989), leaving tion was less frequent. Nonetheless, an inverse, although not the question unresolved. So far, 2 large prospective studies statistically significant, relation was noted between consump- have examined the relation between dietary fat and breast cantion of poached fish and breast cancer risk. Women who re- cer risk, and both provide no epidemiological evidence for a ported having poached fish as part of their main meal 5 times positive association (Willett et al., 1987; Jones et al., 1987), as or more per month had an age-adjusted IRR of 0.7 (95% CL, did a third prospective study among Seventh-Day adventists 0.4 and 1 .O) compared to women who ate fish in this form no (Phillips and Snowdon, 1983). more than twice a month. The negative association with Little work has yet been done on the relation between fish poached fish displayed a dose-related gradient (3 categories of intake) of borderline statistical significance (x2 for intake and breast cancer in humans. A recent ecological study trend = 3.56, p = 0.06). Further adjustment for occupational found that per capita fish intake was negatively correlated to status (housewife vs. not housewife) and body mass index ( 2 national incidence rates of breast cancer (Kaizer et al., 1989). Prospective studies, however, have failed to detect any assocategories) did not change the estimates of effect. ciation between fish or seafood intake and risk of breast cancer In addition, we examined the relation between various other (Willett et al., 1987; Hirayama, 1978). food items and breast cancer risk. There was no association In our study, approximately 95% of the participants rewith daily intake of products such as milk, bread and butter, weekly consumption of eggs and oranges, or with the fre- sponded to the dietary questionnaire. Although dietary habits of the remaining 5% may depart from those of the responders, quency of having potatoes as part of the main meal. it seems unlikely that they would materially affect the associations detected with breast cancer. The response to the question DISCUSSION on overall fish intake confirmed the importance of fish in the In this prospective study, the risk of breast cancer was 80% Norwegian diet, but the lack of inter-person variation prehigher among women who reported an overall frequency of 5 cluded discrimination of breast cancer risk attributable to difor more main meals with meat per week than among those who ferent categories of fish intake. In contrast, the specific queshad meat dinners no more than twice a week. There was no tion on poached fish intake showed considerable variation association between overall intake of fish as part of the main within the population, and the tendency for an inverse relation
in the reference group, typically the category with lowest frequency. The precision of the IRR estimates was assessed by 95% confidence limits using Miettinen's test-based method (Kleinbaum et al., 1982). Adjusting for the effect of age (5year age categories of person years), adjustment for other covariates, and testing for linear trend followed the MantelHaenszel procedures (Rothman, 1986).
TABLE 1 - AGE-ADJUSTED INCIDENCE RATE RATIO (IRR) OF BREAST CANCER, ACCORDING TO THE FREQUENCY OF MAIN MEAL CONTAINING MEAT'
Age (at entry)
35-39 Cases Person years 4Cbl.4 Cases Person years 45-5 1 Cases Person years Total Cases Person years Incidence rate ratio 95% Confidence limits
Overall meat
S 2 timedweek
x2
3-4 timedweek
a5 timedweek
10 11,104
22 34,542
9 6,313
4 10,103
35 33,735
8 5,914
12 12,113
42 40,317
10 6,872
26 33,320 1 .o
99 108,594 1.2 (0.8, 1.8)
27 19,099 1.8 (1.1, 3.1)
mnd
4.30 p = 0.04
'Data are based on 152 cases of breast cancer that occurred during 11 to 14 years of follow-up among 14,500 Norwegian women who were 35-51 years of age at food frequency inquiry.
14
VATTEN ET AL. TABLE U - AGE-ADJUSTED INCIDENCE RATE RATIO (RR)OF BREAST CAYCER, ACCORDING TO THE FREQUENCY OF MAIN MEAL CONTAINING FISH
Overall fish
Age (at entry)
S 2 timeslweek
35-39 Cases Person years 4 w Cases Person years 45-5 1 Cases Person years Total Cases Person years Incidence rate ratio (IRR) 95% Confidence limits
>2 timeslweek
30 38,005
11 13,954
30 35,644
17 14,108
43 41,821
21 17,481
103 115,470 1.0
49 45,543 1.2 (0.8, 1.7)
X=
trend
1.39 p = 0.24
Poached fish
Cases Person years Incidence rate ratio 95% Confidence limits
Publication of the International Union Against Cancer Publication de I'Union lnternationale Contre 1e Cancer
FREQUENCY OF MEAT AND FISH INTAKE AND RISK OF BREAST CANCER IN A PROSPECTIVE STUDY OF 14,500 NORWEGIAN WOMEN Lars J. VATTEN'.2,4,5,Kari sOLVOLL3 and Elin B. L6KEN3 'Department of Oncology, University Hospital, N-7006 Trondheim; 2The Norwegian Cancer Registry, Montebello, N-0310 Oslo 3; and 'Sectionfor Dietary Research, Institute of Nutrition Research, University of Oslo, N-0317 Oslo 3, Norway. The association between the frequency of meat and fish intake and the incidence rate of breast cancer has been analyzed in 152 incident cases that developed among 14,500 Norwegian women during I I to 14 years of follow-up. A t the time of dietary inquiry they were between 35 and 51 years of age. A positive association was observed between the frequency of overall meat intake and breast cancer risk. There was an age-adjusted incidence rate ratio (IRR) of 1.8 (95% confidence limits, 1.1 and 3.1) for women who had a main meal with meat 5 times or more per week compared to women who had 2 meat dinners or less per week, and this associationdisplayed a linear trend (x' trend = 4.30, p = 0.04). No association was detected between the overall frequency of fish for dinner and breast cancer risk (x' trend = 1.39, p = 0.24), but there was an inverse relation with the frequency of main meals containing fish in poached form. The age-adjusted IRR was 0.7 (95% confidence limits, 0.4 and 1.0) for women who had poached fish for dinner at least 5 times per month compared to women who had fish in this form twice monthly or less often trend = 3.56, p = 0.06). The positive association with meat may be in accordance with the hypothesis that dietary fat increases the risk of breast cancer. Although there was no association with overall fish intake, the inverse relation with poached fish might deserve further investigation.
(x'
Dietary studies of breast cancer have typically focused on the hypothesis that there is a positive association between consumption of fat and breast cancer risk (Rohan and Bain, 1987). The strong correlation between per capita fat consumption and national incidence rates of breast cancer yields ecological evidence for a positive association with dietary fat (Armstrong and Doll, 1975; Waterhouse et al., 1982). Animal experiments have supported this association, showing that both type and amount of fat intake may influence incidence and growth of mammary tumours (Tannenbaum and Silverstone, 1953; Wynder et a l . , 1986). Prospective epidemiological studies (Willett et al., 1987; Jones et al., 1987), however, have failed to replicate any positive association based on individual information of dietary intake. The hypothesis that dietary fish intake is negatively associated with the risk of breast cancer has not been confirmed in human studies based on individual dietary information. One correlation study found a negative association between fish consumption and incidence and mortality rates of breast cancer between different countries (Kaizer et al., 1989). The international variation shows that, in certain countries where fish intake is high (e.g. Japan), the incidence rate of breast cancer is comparatively low. Since animal experiments have suggested that fish oils (omega-3 fatty acids) both protect against the occurrence and slow down the growth of mammary carcinomas in rodents (Kannali et al., 1984), it is important to examine the relation between dietary fish intake and breast cancer risk in humans. In this prospective study of 14,500 Norwegian women, we have examined the relation between the frequency of overall meat and fish consumption and the subsequent risk of developing breast cancer during a mean follow-up time of 12 years.
49 years living in 3 separate counties in Norway were invited to participate in a health screening examination organized by the National Health Screening Service (Bjartveit et al., 1979, 1983). Its main objective was to collect information on known and suspected risk factors for cardiovascular disease and hence, no information on factors usually associated with breast cancer risk, such as age at menarche, age at first birth, or exact age at menopause, was collected. A total of 24,617 women (93.8%) attended the screening, and every participant in one county and subsamples from the 2 other counties received a dietary questionnaire, which was filled in and returned by 14,729 women (95%). The official 11-digit person number of Norwegian subjects facilitated linkage to the Cancer Registry in order to identify 152 incident cases of breast cancer that had been diagnosed and reported during 11 to 14 years of follow-up. To reduce a potential bias due to preclinical changes in dietary habits, 171 cancer cases (including breast cancer) that had occurred prior to or during the calendar year of examination were excluded. Fifty-eight questionnaires were excluded for technical reasons, thus giving a total of 14,500 women eligible for analysis. About 60 food frequency questions covered a limited number of food items, which have been described elsewhere (Solvoll et d.,1989). Since the entire diet was not included, computation of energy or specific nutrient intake was not possible. The reproducibility of the dietary questionnaire has been tested among a group of women who completed the questionnaire on two occasions with an interval of 1 month (L@kenand Solvoll, 1987). Information from the questionnaire has also been compared to data from a 24-hr dietary recall among a subsample of the study participants (Solvoll, 1983). In general, it was concluded that the food frequency questionnaire produced fairly reliable information on intake of food items that were consumed on a regular, daily basis (e.g., milk, bread, coffee). The quality of the information related to main meal dishes (e.g. fish, meat) and food items of which consumption is typically less frequent and more irregular, however, could not be appropriately validated by the 24-hr recall method. For each person belonging to a certain category of food intake, observation years at risk of developing breast cancer were computed as the number of years accumulated from the screening examination until withdrawal in the year of diagnosis, at death from another cause, or at the end of follow-up, to allow comparison of person-time-based incidence rates of breast cancer for different categories of each food item. Incidence rate ratios (IRR) were computed as the rate in a specific food frequency category divided by the estimated rate
41n collaboration with The National Health Screening Service, P.O. Box 8155 Dep., Oslo 1, Norway.
5To whom reprint requests should be sent, at the Department of Oncology, University Hospital, N-7G06 Trondheim, Norway.
SUBJECTS AND METHODS
Between 1974 and 1977, all the men and women aged 35 to
Received: February 5 , 1990.
13
COHORT STUDY ON DIET A N D BREAST CANCER
meal and risk of breast cancer. Nonetheless, there was a 30% reduction in breast cancer risk associated with having fish in poached form as part of one's main meal 5 times or more per month compared to having poached fish no more than 1 or 2 times a month. The inverse relation with poached fish was not statistically significant, but the positive association with overall meat intake appears less likely to be due to chance. However, in view of the many food items tested, it cannot be excluded that a RESULTS statistically significant finding may appear as a chance result Table I shows that there was a positive association between due to multiple comparisons. the overall intake of dinners made from meat and breast cancer Since meat is one of the important sources of fat in the risk. Women who had meat dinners 5 times or more per week had an age-adjusted IRR of 1.8 (95% C.L., 1 . 1 and 3.1) com- Norwegian diet, the observed positive association between the pared to women who had 2 or less meat dinners per week. The frequency of overall meat consumption and breast cancer risk test for linear trend associated with overall meat intake (3 may reflect an effect of dietary fat, which has been widely categories) was statistically significant (x2 for trend = 4.30, studied in humans (Rohan and Bain, 1987). Correlation studies p = 0.04). Further adjustment for body mass index did not between countries support this result, showing a strong association between per capita fat consumption and national incimaterially alter the estimates of effect. dence rates of breast cancer (Armstrong and Doll, 1975). FurThere was no association between the frequency of overall ther support for the association with dietary fat can be derived fish intake and risk of breast cancer (Table 11). Women who from animal experiments (Wynder et al., 1986). Case-control reported having fish as part of their main meal more often than studies have yielded results in both directions (Lubin et al., twice a week had an incidence rate ratio (IRR) of 1.2 (95%CL, 1981; Grahametal., 1982; Talamani etal., 1984; Lubinetal., 0.8 and 1.7) compared to women whose overall fish consump- 1986; Katsouyanni et al., 1986; Toniolo et al., 1989), leaving tion was less frequent. Nonetheless, an inverse, although not the question unresolved. So far, 2 large prospective studies statistically significant, relation was noted between consump- have examined the relation between dietary fat and breast cantion of poached fish and breast cancer risk. Women who re- cer risk, and both provide no epidemiological evidence for a ported having poached fish as part of their main meal 5 times positive association (Willett et al., 1987; Jones et al., 1987), as or more per month had an age-adjusted IRR of 0.7 (95% CL, did a third prospective study among Seventh-Day adventists 0.4 and 1 .O) compared to women who ate fish in this form no (Phillips and Snowdon, 1983). more than twice a month. The negative association with Little work has yet been done on the relation between fish poached fish displayed a dose-related gradient (3 categories of intake) of borderline statistical significance (x2 for intake and breast cancer in humans. A recent ecological study trend = 3.56, p = 0.06). Further adjustment for occupational found that per capita fish intake was negatively correlated to status (housewife vs. not housewife) and body mass index ( 2 national incidence rates of breast cancer (Kaizer et al., 1989). Prospective studies, however, have failed to detect any assocategories) did not change the estimates of effect. ciation between fish or seafood intake and risk of breast cancer In addition, we examined the relation between various other (Willett et al., 1987; Hirayama, 1978). food items and breast cancer risk. There was no association In our study, approximately 95% of the participants rewith daily intake of products such as milk, bread and butter, weekly consumption of eggs and oranges, or with the fre- sponded to the dietary questionnaire. Although dietary habits of the remaining 5% may depart from those of the responders, quency of having potatoes as part of the main meal. it seems unlikely that they would materially affect the associations detected with breast cancer. The response to the question DISCUSSION on overall fish intake confirmed the importance of fish in the In this prospective study, the risk of breast cancer was 80% Norwegian diet, but the lack of inter-person variation prehigher among women who reported an overall frequency of 5 cluded discrimination of breast cancer risk attributable to difor more main meals with meat per week than among those who ferent categories of fish intake. In contrast, the specific queshad meat dinners no more than twice a week. There was no tion on poached fish intake showed considerable variation association between overall intake of fish as part of the main within the population, and the tendency for an inverse relation
in the reference group, typically the category with lowest frequency. The precision of the IRR estimates was assessed by 95% confidence limits using Miettinen's test-based method (Kleinbaum et al., 1982). Adjusting for the effect of age (5year age categories of person years), adjustment for other covariates, and testing for linear trend followed the MantelHaenszel procedures (Rothman, 1986).
TABLE 1 - AGE-ADJUSTED INCIDENCE RATE RATIO (IRR) OF BREAST CANCER, ACCORDING TO THE FREQUENCY OF MAIN MEAL CONTAINING MEAT'
Age (at entry)
35-39 Cases Person years 4Cbl.4 Cases Person years 45-5 1 Cases Person years Total Cases Person years Incidence rate ratio 95% Confidence limits
Overall meat
S 2 timedweek
x2
3-4 timedweek
a5 timedweek
10 11,104
22 34,542
9 6,313
4 10,103
35 33,735
8 5,914
12 12,113
42 40,317
10 6,872
26 33,320 1 .o
99 108,594 1.2 (0.8, 1.8)
27 19,099 1.8 (1.1, 3.1)
mnd
4.30 p = 0.04
'Data are based on 152 cases of breast cancer that occurred during 11 to 14 years of follow-up among 14,500 Norwegian women who were 35-51 years of age at food frequency inquiry.
14
VATTEN ET AL. TABLE U - AGE-ADJUSTED INCIDENCE RATE RATIO (RR)OF BREAST CAYCER, ACCORDING TO THE FREQUENCY OF MAIN MEAL CONTAINING FISH
Overall fish
Age (at entry)
S 2 timeslweek
35-39 Cases Person years 4 w Cases Person years 45-5 1 Cases Person years Total Cases Person years Incidence rate ratio (IRR) 95% Confidence limits
>2 timeslweek
30 38,005
11 13,954
30 35,644
17 14,108
43 41,821
21 17,481
103 115,470 1.0
49 45,543 1.2 (0.8, 1.7)
X=
trend
1.39 p = 0.24
Poached fish
Cases Person years Incidence rate ratio 95% Confidence limits
