Environment and Breast Cancer: Science Review

Evidence From Humans
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Birthweight, parental age, birth order and breast cancer risk in African-American and white women: a population-based case-control study
Hodgson, M. E., Newman, B., Millikan, R. C. Breast Cancer Res. 2004. 6:6, R656-67.
Topic area
Early life exposures
Study design
Population based case-control
Study Participants
Number of Cases
Birthweight: 191; maternal age: 263; paternal age: 251
Menopausal Status
The menopausal status of women included in this study is listed here.
Number of Controls
Controls: Birthweight:161; maternal age: 235; paternal age: 206
Participant selection: Inclusion and exclusion criteria
Criteria used to select participants in the study.
Carolina Breast Cancer Study In: Cases:Women who were mentally competent and resident in the study area at the time of selection with a first diagnosis of histologically confirmed breast cancer, for birthweight analysis women who were born in North Carolina on or after 1949, for parental age analysis were restricited to women with parental age available on birth records and under 48 years of age at selection/diagnosis In: controls: Women identified by North Carolina Division of Motor Vehicles and/or Health Care Financing Administration and had no previous or current history of breast cancer and matched by race and 5-years age group to cases. Ex: Women who had any of the following indicators of a possibly poorly measured birthweight: non-institutional birth, birth attendant other than physician, and birthweight recorded only in pounds
Comment about participation selection
Oversampling of African-American women and of women <50 years of age; Set up a general case definition and then restricted the definition for each exposure subgroup, very confusing to analyse results
Exposure Investigated
Exposures investigated
Birthweight, maternal age at birth, paternal age at birth
Exposure assessment comment
28% of African-American women and 7.4% of white women had a birth weight only in pounds (no ounces), excluded in the restricted dataset
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.
White, African-American
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.
Alcohol consumption, family history of breast cancer, parity, menopausal status
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
Logistic regression model adjusted for age, race, sampling fractions, history of previous biopsy, adult BMI and other intrauterine exposures. Adjusted OR with 95% CI, birthweight: race specific tertiles: upper tertile vs central tertile; (white: <3062g, 3
Strength of associations reported
Birthweight:: 0.7 (0.4-1.2); maternal age: 3.0 (1.8-5.2); paternal age: 1.5 (0.7-3.2)
Results Comments
A weak inverse associatin with higher birthweight. For white women in the study there was no overall association between birthweight and breast cancer. Older maternal age exhibited a moderate positive association with breast cancer. Paternal age was not associated with breast cancer.
INTRODUCTION: Much recent work has focused on hypotheses that very early life exposures influence adult cancer risk. For breast cancer it has been hypothesized that high in utero estrogen exposure may increase risk. METHODS: We used data from the Carolina Breast Cancer Study, a population-based case-control study of incident breast cancer in North Carolina, to examine associations for three possible surrogates of high prenatal estrogen exposure: weight at birth, maternal age, and birth order. We also examined paternal age. Birthweight analyses were conducted for white and African-American women born in North Carolina on or after 1949 (196 cases, 167 controls). Maternal age was analyzed for US born participants younger than 49 years of age (280 cases, 236 controls). RESULTS: There was a weak inverse association between birthweight in the highest tertile and breast cancer overall (odds ratio [OR] 0.7, 95% confidence interval [CI] 0.4-1.2), although associations differed by race (OR 0.5, 95% CI 0.2-1.0, and OR 1.0, 95% CI 0.5-2.1 for African-American and white women, respectively). For maternal age there was an approximately threefold increase in risk in women whose mothers were older than 22 years of age, relative to 19-22 years of age, when the women were born. After adjustment for maternal age, older paternal age increased risk in the oldest and youngest age categories (relative to 23-27 years of age at the woman's birth: OR 1.6, 95% CI 0.8-3.1 for age 15-22 years; OR 1.2, 95% CI 0.7-2.2 for age 28-34 years; and OR 1.5, 95% CI 0.7-3.2 for age 35-56 years). There was no association with older paternal age for white women alone. After adjustment for maternal age (265 cases, 224 controls), a birth order of fifth or higher relative to first had an inverse association with breast cancer for women younger than 49 years old (OR 0.6, 95% CI 0.3-1.3). CONCLUSION: Although the CIs are wide, these results lend support to the possibility that the prenatal period is important for subsequent breast cancer risk, but they do not support the estrogen hypothesis as a unifying theory for the influence of this period.
Author address
Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. ehodgson@email.unc.edu