Hodgson M Elizabeth, Newman Beth, Millikan Robert C
Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Breast Cancer Res. 2004;6(6):R656-67. doi: 10.1186/bcr931. Epub 2004 Sep 22.
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.
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).
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).
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.
近期许多研究聚焦于生命早期暴露影响成人癌症风险的假说。对于乳腺癌,有人提出子宫内高雌激素暴露可能会增加风险。
我们使用了卡罗来纳乳腺癌研究的数据,这是一项基于北卡罗来纳州新发乳腺癌的人群病例对照研究,以检验高产前雌激素暴露的三种可能替代指标之间的关联:出生体重、母亲年龄和出生顺序。我们还研究了父亲年龄。对1949年及以后在北卡罗来纳州出生的白人和非裔美国女性进行了出生体重分析(196例病例,167例对照)。对美国出生的49岁及以下参与者进行了母亲年龄分析(280例病例,236例对照)。
最高三分位数的出生体重与总体乳腺癌之间存在微弱的负相关(优势比[OR]为0.7,95%置信区间[CI]为0.4 - 1.2),尽管不同种族的关联有所不同(非裔美国女性的OR为0.5,95% CI为0.2 - 1.0,白人女性的OR为1.0,95% CI为0.5 - 2.1)。对于母亲年龄,母亲在其出生时年龄大于22岁的女性,相对于母亲年龄在19 - 22岁的女性,风险增加约三倍。在调整母亲年龄后,父亲年龄较大在最年轻和最年长年龄组中增加了风险(相对于女性出生时父亲年龄在23 - 27岁:15 - 22岁年龄组的OR为1.6,95% CI为0.8 - 3.1;28 - 34岁年龄组的OR为1.2,95% CI为0.7 - 2.2;35 - 56岁年龄组的OR为1.5,95% CI为0.7 - 3.2)。仅白人女性与父亲年龄较大无关联。在调整母亲年龄后(265例病例,224例对照),49岁及以下女性中出生顺序为第五或更高相对于第一与乳腺癌呈负相关(OR为0.6,95% CI为0.3 - 1.3)。
尽管置信区间较宽,但这些结果支持产前时期对后续乳腺癌风险很重要的可能性,但不支持雌激素假说作为这一时期影响的统一理论。