Birthweight, parental age, birth order and breast cancer risk in African-American and white women: a population-based case–control study

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.