Environment and Breast Cancer: Science Review

Evidence From Humans
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DDT and breast cancer in young women: new data on the significance of age at exposure
Cohn, B. A., Wolff, M. S., Cirillo, P. M., Sholtz, R. I. Environ Health Perspect. 2007. 115:10, 1406-14.
Topic area
Environmental pollutant - Organochlorine pesticides DDT DDE
Study design
Nested case-control
Funding agency
NCI National Institute for Child Health and Develo
Study Participants
Menopausal Status
The menopausal status of women included in this study is listed here.
No analyses by menopausal status (all cases in analysis were premenopausal)
Number of Controls
Controls: 129
Participant selection: Inclusion and exclusion criteria
Criteria used to select participants in the study.
Participants were from the Child Health and Development cohort, who were recruited between 1959 to 1967 as residents of Oakland, California, members of the Kaiser Permanente Health Plan, and sought obstetric care. Breast cancer cases were identified from the original study cohort by linkage to the California Cancer Registry and California Vital Status Records. Cases were women with incident invasive or noninvasive breast cancer diagnosed before 50 years of age, or death due to breast cancer before age 50. Controls were matched to cases on birth year, and were free of breast cancer at the age of diagnosis for the matching case. Other exclusion criteria included insufficient serum quantity for analysis and missing BMI information.
Exposure Investigated
Exposures investigated
Lipid-adjusted serum p,p'-DDE, o,p'-DDT, and p,p'-DDT collected within 1-3 days of delivery (>80%) or during the third trimester of pregnancy between 1959 and 1967.
Exposure assessment comment
This study had subanalyses for exposure to DDT <14 years of age, allowing for assessment of early life influence. Serum was collected during years of DDT use (<1970). Follow-up in 2001 allowed for a long latency period. 1945 was the first year DDT was used in the US, so age in 1945 represents the age of first possible exposure.
Early life exposures considered
Yes, exposure <14 years of age
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, race/ethnicity, number of previous pregnancies, age at first pregnancy ≥7 months, menarche before 12 years of age, BMI, breastfeeding after the observed pregnancy, year of blood draw, and age at blood draw
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
Women of all ages in 1945, mutually adjusted for o,p'-DDT:
2nd tertile vs. 1st tertile: aOR 2.0 (95% CI 0.9-4.2)
3rd tertile vs. 1st tertile: aOR 3.0 (95% CI 1.3-6.8)

Women <14 years of age in 1945, mutually adjusted for o,p'-DDT:
2nd tertile vs. 1st tertile: aOR 2.6 (95% CI 1.1-6.4)
3rd tertile vs. 1st tertile: aOR 5.0 (95% CI 1.7-14.8)

Women of all ages in 1945, mutually adjusted for o,p'-DDT:
2nd tertile vs. 1st tertile: aOR 1.8 (95% CI 1.0-3.4)
3rd tertile vs. 1st tertile: aOR 1.6 (95% CI 0.8-3.4)

Women <14 years of age in 1945, mutually adjusted for o,p'-DDT:
2nd tertile vs. 1st tertile: aOR 2.2 (95% CI 1.0-4.8)
3rd tertile vs. 1st tertile: aOR 2.1 (95% CI 0.8-5.2)
Results Comments
Source and timing of exposure was not definitively determined, but suggestive that the major of exposure occurred through diet and direct contact with insect control. The authors note that information on parity and lifetime lactation duration were missing risk factors. The study had a relatively small sample size, but had unique blood serum samples that were collected prior to most other published studies. Significant protective effect observed for o,p'-DDT in models mutually adjusted for p,p'-DDT. Based on metabolism of the two compounds, p,p'-DDT may be a better marker of past exposure than o,p'-DDT. ORs for p,p'-DDT exposure among women who were < 14 years old in 1945 were not appreciably different in a model controlling for lipids.
BACKGROUND: Previous studies of DDT and breast cancer assessed exposure later in life when the breast may not have been vulnerable, after most DDT had been eliminated, and after DDT had been banned. OBJECTIVES: We investigated whether DDT exposure in young women during the period of peak DDT use predicts breast cancer. METHODS: We conducted a prospective, nested case-control study with a median time to diagnosis of 17 years using blood samples obtained from young women during 1959-1967. Subjects were members of the Child Health and Development Studies, Oakland, California, who provided blood samples 1-3 days after giving birth (mean age, 26 years). Cases (n = 129) developed breast cancer before the age of 50 years. Controls (n = 129) were matched to cases on birth year. Serum was assayed for p,p'-DDT, the active ingredient of DDT; o,p'-DDT, a low concentration contaminant; and p,p'-DDE, the most abundant p,p'-DDT metabolite. RESULTS: High levels of serum p,p'-DDT predicted a statistically significant 5-fold increased risk of breast cancer among women who were born after 1931. These women were under 14 years of age in 1945, when DDT came into widespread use, and mostly under 20 years as DDT use peaked. Women who were not exposed to p,p'-DDT before 14 years of age showed no association between p,p'-DDT and breast cancer (p = 0.02 for difference by age). CONCLUSIONS: Exposure to p,p'-DDT early in life may increase breast cancer risk. Many U.S. women heavily exposed to DDT in childhood have not yet reached 50 years of age. The public health significance of DDT exposure in early life may be large.
Author address
Child Health and Development Studies, Center for Research on Women's and Children's Health, Public Health Institute, Berkeley, California 94709, USA. bcohn@chdstudies.org
Reviewers Comments
A summary was published in the same issue of EHP by Manuel. Additional correspondence was published in 116(4), 2008, by Tarone, with response by the authors. Another correspondence was published in 116(9), 2008.