Environment and Breast Cancer: Science Review

Evidence From Humans
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Growth patterns and the risk of breast cancer in women
Ahlgren, M., Melbye, M., Wohlfahrt, J., Sorensen, T. I. N Engl J Med. 2004. 351:16, 1619-26.
Topic area
Early life exposures - Body size
Study design
Prospective Cohort
Funding agency
DOD; Danish Medical Research Council, Danish Natio
Study Participants
Number of Cases
3,340 (invasive only)
Menopausal Status
The menopausal status of women included in this study is listed here.
Number in Cohort
Cohort: 117,415
Participant selection: Inclusion and exclusion criteria
Criteria used to select participants in the study.
In: women born from 1930 through 1975 who had undergone regular health examinations in school in the municipality of Copenhagen women with complete information on weight and height at 8, 10, 12, 14 years of age, as well as peak growth Ex: women who emigrated, died or changed their surnames before 1968 and could not be linked to the Danish Civil Registration System (CRS); women without complete information on weight and height
Comment about participation selection
Strengths: Long follow-up, anthropometric data obtained from school records; large population-based cohort; lengthy follow up with 3,333,359 person years covered; large number of breast cancer cases (3340); analyzed the association between breast cancer and birth weight, height at age 14, BMI at age 14, and change in height and weight in adolescents; investigated whether growth in specific age intervals increased the risk of breast cancer using the age at peak growth (12 month period beginning 6 months before the estimated age at peak growth) to subdivide the period from 8 to 14 years of age into three intervals Limitations:did not stratify results by menopausal status at diagnosis; did not have information on family history of breast cancer, history of benign breast disease and hormone replacement therapy; inability to analyze adult weight and BMI; information on birth weight was reported by parents of the participants
Exposure Investigated
Exposures investigated
Birth weight, height at age 14, BMI at age 14, change in height and BMI between 8 and 14 years of age; height and weight at 8 years of age
How exposure was measured
Other: measurements from school records and reports from parents of participants
Exposure assessment comment
Birthweight reported by parents
Statistical Analysis
Breast cancer outcome investigated
Primary incident breast cancer
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.
Adequately controlled, Confounders: age, birth cohort, parity, age at first childbirth, age at menarche and calendar period Race, menopausal status, alcohol consumption, family history of breast cancer
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
Cox proportional hazard model adjusted for age and calendar period. No change in effect estimate was found when adjusted for parity and age at first birth. Adjusted RR with 95% CI; follow-up 1998-2001
Strength of associations reported
Highest (median 4.0kg) versus lowest (median 2.5 kg) quintile of birthweight 1.17 (1.02-1.33)
Association between breast cancer and birth weight trend (per kg increase), RR=1.10(1.01-1.20)
Association between breast cancer and height before age 8 trend (per 5 cm increase), RR=1.11(1.07-1.15)
Association between breast cancer and height increase between age 8 to 14 years trends (per 5 cm increase), RR=1.17(1.09-1.25)
Association between breast cancer and height at age 14 trend (per 5 cm increase), RR=1.11(1.08-1.15)
Association between breast cancer and BMI at age 14 trend (trend per unit), RR=0.97(0.96-0.98)
Results Comments
High birthweight is an independent risk factor for breast cancer
Author address
Department of Epidemiology Research, Danish Epidemiology Science Center, Statens Serum Institut, Copenhagen, Denmark. abk@ssi.dk