Environment and Breast Cancer: Science Review

Evidence From Humans
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Dietary carotenoids and vitamins A, C, and E and risk of breast cancer
Zhang, S., Hunter, D. J., Forman, M. R., Rosner, B. A., Speizer, F. E., Colditz, G. A., Manson, J. E., Hankinson, S. E., Willett, W. C. J Natl Cancer Inst. 1999. 91:6, 547-56.
Study design
Prospective cohort
Funding agency
Not reported
Study Participants
Number of Cases
2,697/ 784 premenopausal and 1,913 postmenopausal
Menopausal Status
The menopausal status of women included in this study is listed here.
Pre menopausal
Post menopausal
Number in Cohort
Cohort: 83,234
Participant selection: Inclusion and exclusion criteria
Criteria used to select participants in the study.
In: Female nurses who were 30-55 years old in 1976 and enrolled in the Nurses' Health Study Ex: Response to the 1980 dietary questionnaire had implausible total energy intake (<500 or >3500 kcal/day), if they left 10 or more food items blank, or if they had a previous diagnosis of cancer (other than non-melanoma skin cancer)
Comment about participation selection
Good follow up with 4 dietary questionnaires over 10 years
Exposure Investigated
Exposures investigated
Carotenoids, vitamins A,C,E
How exposure was measured
Questionnaire, self-administered, FFQ
Exposure assessment comment
Lower quintile of intake for Vit A include the dietary reference intake (daily recommendation): all are high consumer of Vit A
Statistical Analysis
Ethnic groups with separate analysis
If this study provided a separate analysis by ethnic or racial group, the groups are listed here.
Confounders considered
Other breast cancer risk factors, such as family history, age at first birth, and hormone replacement therapy use, that were taken into account in the study.
Not considered: Race
Genetic characterization included
If the study analyzed relationships between environmental factors and inherited genetic variations, this field will be marked Yes. No, if not.
Description of major analysis
RR with 95% CI, highest versus lowest quintile, stratified by menopausal status, family history of breast cancer, or alcohol intake, non-supplement users analyzed separately from supplement users , follow-up 14 years
Strength of associations reported
Total fruits and vegetables: 0.77 (0.58 - 1.02)
Fruits: 0.74 (0.45 - 1.24)
Vegetables: 0.64 (0.43 - 0.95)
β carotene food only: 0.84 (0.67-1.05)
Total vitamin A food only: 0.82 (0.65-1.04)
Total vitamin C food only: 1.01(0.81-1.26)
Total vitamin E food only: 0.81 (0.4-1.02)

Total fruits and vegetables: 1.03 (0.81 - 1.31)
Fruits: 0.84 (0.64 - 1.09)
Vegetables: 1.02 (0.85- 1.24)
β carotene food only: 0.94 (0.81-1.09)
Total vitamin A food only: 1.03 (0.89-1.19)
Total vitamin C food only: 1.06 (0.91-1.22)
Total vitamin E food only: 0.96 (0.83-1.11)
Results Comments
Beta-carotene from food and supplement and total vitamin A from foods were inversely associated with risk of premenopausal breast cancer. These inverse associations were strongest among women at elevated risk due to a positive family history of breast cancer or consumption of greater than or equal to 15g/day of alcohol. Intake of these nutrients had no appreciable overall associations with risk of postmenopausal breast cancer, but they had inverse relationships among postmenopausal women currently taking hormones. In addition, the use of supplements of vitamin A, C, and E and multivitamins was not associated with overall risk of cancer.
Author address
Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA. Shumin.Zhang@channing.harvard.edu
Reviewers Comments
Lack of interaction between vitamins