Evidence From Humans
Print this page
Interaction of nitrate and folate on the risk of breast cancer among postmenopausal women
Inoue-Choi, M., Ward, M. H., Cerhan, J. R., Weyer, P. J., Anderson, K. E., Robien, K. Nutr Cancer. 2012. 64:5, 685-94.
Topic area
Environmental pollutant - Drinking water
Study design
Prospective cohort
Study Participants
Menopausal Status
The menopausal status of women included in this study is listed here.
All women in the study were postmenopausal
Number in Cohort
Cohort: 20,147
Participant selection: Inclusion and exclusion criteria
Criteria used to select participants in the study.
Women in the Iowa Women's Health Study (IWHS) who responded to a questionnaire mailed in 1986 to women randomly selected from Iowa driver's license records. This analysis included postmenopausal women free of cancer (except non-melanoma skin cancer) at baseline who had never had a previous mastectomy or partial breast resection, who were active in the study in 1989 and had used their public or private water supply for at least 10 years. Cases were identified from State Health Registry of Iowa's cancer database through 2008.
Exposures investigated
Average nitrate measurements in Iowa municipal water 1955-1988, from historical database. Individual nitrate intake estimated as average municipal nitrate level in multiplied by assumed daily water consumption of 2 L/day.
How exposure was measured
Environmental sample Questionnaire, self-administered
Breast cancer outcome investigated
Primary incident breast cancer
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.
Age, total energy intake, BMI, WHR, education, smoking, physical activity, family history of breast cancer, estrogen use, total intakes of folate, vitamin C and E and flavinoids, intakes of cruciferae and red meat.
Genetic characterization included
If the study analyzed relationships between environmental factors and inherited genetic variations, this field will be marked Yes. No, if not.
Strength of associations reported
Daily nitrate intake from water (mg/2L):
Q2 HR 1.07 (95% CI 0.89-1.28)
Q3 HR 0.96 (95% CI 0.80-1.16)
Q4 HR 1.05 (95% CI 0.88-1.27)
Q5 HR 1.14 (95% CI 0.95-1.36)
Results Comments
OR for private well users vs quintile 1 of public water users was very similar to Q5 vs Q1 among public water users (OR =1.14; 95% CI: 0.97-1.34). No nitrate measurements were available for private well users, but authors note private wells are often in rural agricultural areas. OR was significant for Q5 vs Q1 among women with higher (≥ 400μg/d) folate intake (OR = 1.40; 95% CI: 1.05-2.82), while there was no association among women with lower (< 400 μg/d) folate intake (OR = 1.00; 95% CI: 0.83-1.24). The authors note that folate has both anticancer and tumor promoting actions, so hypothesize this interaction could reflect the latter.
Author address
Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, Minnesota 55454, USA. inou0021@umn.edu
Privacy notice   |   Copyright statement