alcohol consumption and breast cancer risk in denmark

Alcohol Consumption and Breast Cancer Risk in DenmarkAuthor(s): Marianne EwertzSource: Cancer Causes & Control, Vol. 2, No. 4 (Jul., 1991), pp. 247-252Published by: SpringerStable URL: http://www.jstor.org/stable/3553408 .

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Cancer Causes and Control, 2, 247 - 252

Alcohol consumption and breast cancer risk in Denmark

Marianne Ewertz

(Received 23 April 1991; accepted 2 May 1991)

The influence of alcohol consumption on breast cancer risk was evaluated in a population-based case-control study, including 1,486 cases diagnosed over a one-year (1983-84) period in Denmark. Cases were identified from the files of the nationwide clinical trial of the Danish Breast Cancer Cooperative Group and the Danish Cancer Registry. The control group was an age-stratified random sample of 1,336 women from the general population. Data on risk factors were collected by self-administered questionnaires. The association of alcohol consumption with breast cancer risk varied with age and dietary fat intake. Among women aged 50-59 years, with a fat intake in the lowest quartile, the risk of breast cancer increased with increasing consumption of alcohol. A consumption of 24 g or more per day was associated with an 18-fold increased risk compared with abstainers. For women in other age groups, alcohol consumption had no significant association with breast cancer risk.

Key words: Age, alcohol, breast neoplasms, Denmark, dietary fat.

Introduction

Prior to 1982, little attention was paid to the association of alcohol consumption with risk of developing breast cancer. Since that time, the issue has been addressed in at least five cohort studies'- and 20 case- control studies.6-25 Longnecker et al26 performed a meta-analysis of data available up to 1988 and observed a dose-response relation of increasing breast cancer risk with increasing alcohol consumption. Relative to abstaining, a daily consumption of 24 g of ethanol (or about two drinks) was associated with a risk of 1.4 in the case-control data and 1.7 in the cohort data. Results of some later studies21-24 agree with these risk estimates, though otherss5'8-2025 do not.

To evaluate the influence of diet, alcohol, and hormones on breast cancer risk, a population-based case- control study was conducted in Denmark, including almost all incident cases over a one-year period. The risk associated with use of exogenous estrogens,27 reproductive factors,28 diet,2" and smoking"3 has been presented elsewhere. The present paper examines the association of alcohol consumption with breast cancer risk.

Materials and methods Details of the study population and methods have been described.28'29 The cases consisted of 1,694 women, aged less than 70 years, diagnosed with breast cancer in Denmark between 1 March 1983 and 29 February 1984. They were identified from the files of the nationwide, clinical breast-cancer trial of the Danish Breast Cancer Cooperative Group and the Danish Cancer Registry. As controls, an age-stratified random sample of 1,705 women was selected from the general population identified from the Central Population Register. Women with a breast cancer predating the study period were excluded from both case and control groups.

A total of 1,486 cases (88 percent) and 1,336 controls (78 percent) completed self-administered questionnaires on potential risk factors, including alcohol consumption. These were mailed to the cases one year after their month of diagnosis. To promote compar- ability of recollection in the controls, the preselected pool was divided into monthly batches which were assigned the same date of diagnosis as the cases.

Usual consumption of alcoholic beverages in the

The author is with the Danish Cancer Registry, Institute of Cancer Epidemiology, Danish Cancer Society, Rosenvaengets Hovedvej 35, Box 839 DK-2100 Copenhagen 0, Denmark. The study was funded by The Danish Cancer Society, the Danish Medical Research Council, and Astrid Thaysen's Legat.

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M. Ewertz

year prior to diagnosis was assessed from open-ended questions on how often (per day, week, or month) the subjects drank beer (330 ml bottle), table wine (120 ml glass), fortified wine such as sherry and port (40 ml glass), and spirits (20 ml glass). Frequencies less than once per month were recorded as 'never'. Some women were not able to indicate any frequency of consumption but stated that they only drank the particular item at parties. For this group, the lowest frequency-of consumption was assigned, i.e. once per month. Finally, the women were asked to indicate whether their current alcohol consumption was higher, lower, or the same as 10-15 years ago. Intake of ethanol for each woman was computed as the sum of the contribution from each type of drink. Based on average alcohol concentrations, the contributions were estimated as 11.6 g for a bottle of beer, 11.4 g for a glass of table wine, 5.7 g for a glass of fortified wine, and 6.3 g for a glass of spirit.3

The measure of association between study factors and breast cancer was the relative risk (RR) estimated from odds ratios. Comparisons of cases and controls were made by logistic regression techniques32 using the statistical package EGRET for the computations. This provides RR estimates with corresponding estimates of precision, adjusted for the effect of other factors where necessary, including tests for interaction between risk factors. In the case of ordered variables, significance also was evaluated by testing for a linear trend in RR. Although cases and controls were frequency-matched on age at diagnosis, all RR estimates were adjusted for age.

Results Table 1 presents the information on current consumption of specific types of alcoholic beverage. Compared with nondrinkers, elevated risks were seen for consumptions exceeding seven bottles of beer or glasses of table wine, and with three glasses of fortified wine per week, but none of the associations was significant. Indications of prior consumption did not appear to be related to risk of breast cancer. However, about a third of cases and controls did not state their prior consumption.

Analyses of consumption of ethanol from all beverages showed a considerable variation in relation to breast cancer risk factors (Table 2). The frequency of an alcohol consumption of 24 g or more per day was higher for women living in the capital and capital suburbs, for women with a longer education, for ever- smokers, for ever-users of oral contraceptives, and for leaner women. This pattern was similar for cases and controls and did not confound the association between

Table 1. Risk of breast cancer associated with current consumption of alcoholic beverages

Type of Cases Controls Age-adjusted alcoholic No. % No. % RR (95% CI)" beverage

Beer, bottles per week 0 473 32 401 30 1.0 (R)b <3 565 38 520 39 0.94 (0.79-1.13) 3-6 104 7 91 7 0.99 (0.72-1.35) 7 65 4 65 5 0.84 (0.58-1.22) >7 43 3 29 2 1.27 (0.78-2.07) Unstated 236 16 230 17 -

Table wine, glasses per week 0 279 19 246 18 1.0 (R) <3 725 49 659 49 1.00 (0.81-1.23) 3-6 151 10 141 11 0.99 (0.74-1.32) 7 60 4 53 4 1.01 (0.67-1.53) >7 72 5 51 4 1.30 (0.87-1.94) Unstated 199 13 186 14

Fortified wine, glasses per week 0 482 32 453 34 1.0 (R) <3 552 37 505 38 1.03 (0.86-1.23) 3-6 36 2 20 1 1.73 (0.98-3.03) >6 36 2 26 2 1.29 (0.76-2.17) Unstated 380 26 332 25 -

Spirits, glasses per week 0 489 33 434 32 1.0 (R) <3 588 40 548 41 0.96 (0.81-1.15) 3-6 90 6 68 5 1.19 (0.84-1.67) >6 58 4 59 4 0.89 (0.59-1.27) Unstated 261 17 227 17

a Relative risk (95% confidence interval). bR denotes reference category.

alcohol and breast cancer risk. No consistent relationship was observed between alcohol consumption and parity, age at first birth, and dietary p-carotene intake. However, there were significant interactions (P < 0.01) between alcohol consumption and age at diagnosis and dietary fat intake, i.e. the association of alcohol consumption with breast cancer risk differed by age group and fat intake. Whether the interaction between age and alcohol could be explained by menopausal status or years since menopause was tested, but the age-alcohol interaction still remained significant taking the menopause variables into account.

Consequently, an age-stratified analysis was performed and, for each age group, the interaction between alcohol and fat intake was tested. Among women aged less than 50 years at diagnosis (Table 3), no significant interaction between alcohol and fat intake was detected. The risk of breast cancer decreased with increasing consumption of alcohol, though neither the association nor the test for trend was significant. There was a significant trend

248 Cancer Causes and Control. Vol 2. 1991



Alcohol and breast cancer

Table 2. Distribution of alcohol consumption by selected breast cancer risk factors

Risk factors No. of Alcohol consumption (g/day) cases/ 0 1-23 >24

controls cases/ cases/ cases/ controls (%) controls (%) controls (%)

Age of diagnosis, years <50 544/511 10/8 82/84 8/8 50-59 434/395 15/18 77/79 8/3

>60 383/320 24/21 69/75 7/4

Residence at diagnosis Capital 198/113 12/7 74/81 14/12 Suburbs 212/167 10/9 77/83 13/8 Provincial

towns 489/498 17/15 78/81 5/4 Rural areas 462/448 19/17 76/78 5/5

Years of education <8 509/510 25/23 70/75 5/2 8-12 510/450 11/10 83/85 6/5 >12 342/266 8/6 78/82 14/12

Parity 0 203/108 21/15 72/81 7/4 1 199/176 15/11 73/83 12/6 2 529/473 14/13 79/82 7/5 3 279/274 14/14 79/80 7/6 >3 148/192 20/23 76/72 4/5

Age at first birth <20 131/121 21/16 69/79 10/5 20-24 484/511 13/14 80/80 7/6 25-29 393/338 14/13 80/83 6/4

>30 139/139 17/17 75/75 8/8

Use of oral contraceptives No 908/808 19/18 75/78 6/4 Yes 440/404 9/6 81/85 10/9

Menopausal replacement No 915/867 17/14 76/81 7/5 Yes 391/315 13/14 78/78 9/8

Body mass index (W/H2) <20 129/128 12/17 77/75 11/8 20-24 603/558 13/11 81/83 6/6 25-29 389/339 15/12 77/83 8/5

>30 207/179 25/28 68/69 7/3

Dietary fat intake, quartiles 1 (low) 289/317 19/24 73/72 8/4 2 329/308 16/9 78/86 6/5 3 357/295 11/14 82/79 7/6 4 (high) 373/286 17/10 75/83 8/7

Dietary n-carotene intake, quartiles 1 (low) 268/330 21/25 73/70 6/5 2 358/280 17/13 77/83 5/4 3 359/300 13/10 78/83 9/7 4 (high) 361/297 13/9 78/86 9/5

Smoking Never 450/400 20/20 77/77 3/3 Ever 907/823 13/12 77/81 10/7

Table 3. Effect of intake of alcohol and dietary fat on breast cancer risk in women aged less than 50 years at diagnosis

Relative risk' P-value

(95% confidence interval) for linear trend

Alcohol intake (g/day)

0 1.0 (R)b 1-23 0.74 (0.47-1.15) >24 0.63 (0.34-1.17) 0.15

Fat intake

(quartiles) 1 (low) 1.0 (R) 2 1.02 (0.70-1.51) 3 1.19 (0.82-1.74) 4 (high) 1.42 (0.97-2.07) 0.04

Adjusted for age at diagnosis as a continuous variable, place of residence, years of education, parity, and the other variable in the table.

R denotes reference category.

(P = 0.04) of increasing risk with increasing dietary fat intake.

In women aged 50-59 years at diagnosis, there was a significant interaction (P = 0.03) between intake of alcohol and dietary fat (Table 4). Among women in the lowest quartile of fat intake, the risk of breast cancer increased with increasing alcohol consumption, women drinking 24 g or more per day having an 18- fold higher risk than abstainers. The very wide confidence interval reflects that the estimate was based on 14 cases and two controls. For women consuming more dietary fat, a high alcohol consumption did not appear to be associated with the risk of breast cancer. The association of dietary fat intake also varied with alcohol consumption. Among nondrinkers, a high fat intake was associated with increased risk of breast cancer, whereas a decreased risk was noted among those who drank 24 g or more per day. Combining the effects of alcohol and dietary fat-all compared with the lowest intakes of-increased risks, varying from 2.2 to 18.

In the oldest age group, 60 years or more at diagnosis, the interaction between alcohol and fat intake was not significant (Table 5). There was no association between alcohol and breast cancer risk. Increased risks were found for all levels of fat intake, but the estimate for the top quartile was not significant. This was also the case for the test for trend.

Discussion Evaluating the association of alcohol consumption with breast cancer risk, the present study demon- strated a complex interaction with age and dietary fat

Cancer Causes and Control. Vol 2. 1991 249



M. Ewertz

Table 4. Relative riska (95% confidence interval) of breast cancer associated with intake of alcohol and dietary fat in women aged 50-59 years at diagnosis

Fat intake Alcohol intake (g/day) (quartiles) 0 1-23 224 0 1-23 2 24

1 (low) 1.0 (R)b 2.53 (1.11-5.74) 17.9 (3.31-97.0) 2 1.0 (R) 0.63 (0.30-1.35) 1.55 (0.33-7.22) 3 1.0 (R) 1.20 (0.51-2.83) 1.08 (0.25-4.72) 4 (high) 1.0 (R) 0.62 (0.28-1.40) 1.18 (0.24-5.76)

1 1.0 (R) 1.0 (R) 1.0 (R) 2 3.48 (1.28-9.46) 0.87 (0.54-1.41) 0.30 (0.04-2.28) 3 2.84 (0.95-8.45) 1.35 (0.85-2.15) 0.17 (0.02-1.19) 4 5.11 (1.79-14.6) 1.25 (0.78-2.01) 0.33 (0.04-2.60)

1 1.0 (R) 2.53 (1.11-5.74) 17.9 (3.31-97.0) 2 3.48 (1.28-9.46) 2.20 (0.97-5.00) 5.41 (1.13-25.9) 3 2.84 (0.95-8.45) 3.41 (1.52-7.62) 3.06 (0.72-13.0) 4 5.11 (1.79-14.6) 3.17 (1.41-7.11) 6.04 (1.24-29.3)

a Adjusted for age as a continuous variable, place of residence, years of education, and parity. b R denotes reference category. Estimates in the three sections of the table are based on the same numbers

but use different referents.

intake. A subgroup of women was identified, aged 50-59 years with a fat intake in the lowest quartile, in whom the risk of breast cancer rose with increasing alcohol consumption. We found an 18-fold increase for those consuming 24 g or more per day (or about two drinks) compared with abstainers. In other women, alcohol consumption had no significant association with breast cancer risk.

Among studies taking dietary fat intake into account, the present results agree with those of Richardson et a11 who also found a significant interaction between alcohol and fat intake, and that the association with alcohol was most pronounced in women with a low fat intake. In other studies, an increased risk of breast cancer associated with alcohol

Table 5. Effect of intake of alcohol and dietary fat on breast cancer risk in women aged 60 years or more at diagnosis

Relative risk' P-value (95% confidence interval) for linear trend

Alcohol intake (g/day)

0 1.0 (R)b 1-23 0.73 (0.50-1.06) >24 0.95 (0.44-2.07) 0.6

Fat intake (quartiles)

I (low) 1.0 (R) 2 1.69 (1.11-2.57) 3 1.53 (1.00-2.35) 4 (high) 1.43 (0.94-2.18) 0.1

Adjusted for age at diagnosis as a continuous variable, place of residence, years of education, parity, and the other variable in the table.

b R denotes reference category.

consumption was not influenced by adjustment for diet, whether the dietary assessment was relatively simple'0"12,2 or more sophisticated.2'3'16,23

In most studies, the association with alcohol did not vary with age. However, Adami et al"8 detected a slightly decreasing risk with increasing alcohol consumption in women aged less than 45 years. The results of this study go in the same direction although they were not statistically significant. In other stud- ies2,3,12,16 the association of breast cancer risk with alcohol consumption was most pronounced in younger women.

Thus, present findings appear to be at variance with those of most other investigations. It is unlikely that the interaction between alcohol, age, and fat intake arose because of bias related to the selection of cases and controls since the study was population-based. It cannot be ruled out, though, that nonresponders had a consumption of alcohol and fat that differed from women who completed the questionnaire. Although the possibility of information bias cannot be excluded, the data give no evidence for a greater tendency among cases than controls to report changes in alcohol consumption. Errors in the measurement of alcohol consumption generally lead to under-reporting of high consumptions and thus an underestimation of the magnitude of the true association. Finally, the possibility remains that the interactions between alcohol consumption, age, and fat intake in this study were due to chance. Testing the alcohol-fat interaction in each of the three age groups, the possibility of it being significant (P < 0.05) in at least one group, by chance, is 14

percent. There was a remarkable similarity between Danish




Alcohol and breast cancer

and American women in the relation between alcohol consumption and several breast cancer risk factors. In the United States2'3'",'7"9 as well as in Denmark, con- sumers of alcohol tended to be younger, to have more education, to have fewer children, to be lean, to smoke, and to use oral contraceptives. In two of these studies,5'29 alcohol consumption did not affect the risk of breast cancer. In the other three,23,'17 higher risk estimates for alcohol were obtained in lean than in heavy women.

In trying to reconcile the evidence on alcohol consumption and breast cancer risk, the literature2122,2426 seems to support a weak positive association, the risk being in the order of 1.4-1.7 for 24 g or more alcohol per day, corresponding to about two drinks. The risk increase does not seem to be confined to any particular type of beverage, suggesting an effect of alcoholper se. In some studies, including the present, a pronounced risk increase has been observed when women, other- wise at a low risk of developing breast cancer, had a high alcohol consumption.

The carcinogenic action of alcohol is not fully understood" and no biological mechanism has been established to explain how alcohol should affect breast carcinogenesis. Alcohol has a variety of direct as well as indirect effects on sex hormones, through stimu- lation of the pituitary and adrenals to the extraglandular conversion of androgen to

estrogen.?-6 The

interaction between alcohol and fat consumption in this study raises the possibility that high-density lipoprotein cholesterol (HDL-C) may be involved. HDL-C levels correlate positively with intakes of both dietary fat and alcohol. However, the literature does not provide sufficient evidence to conclude whether HDL-C is causally related to breast cancer or is merely associated with risk factors.37

In conclusion, the present study provides some support of a positive association between alcohol and breast cancer risk. The interaction with fat intake illus- trates the importance of considering alcohol as a dietary factor which, as other components of diet, deserves further study.

Acknowledgements-The author thanks Dr O. M. Jensen, the Danish Cancer Registry, Dr H. T. Mourid- sen on behalf of the Danish Breast Cancer Cooper- ative Group, Dr N. E. Day and Mr S. W. Duffy, MRC Biostatistics Unit, Cambridge, UK, for their scientific support, as well as Mrs J. F. Larsen, Mrs G. Mathiesen and Ms S. I. Hartkopp for technical assistance.

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