Intrauterine environment and breast cancer risk in women: A population-based study
Intrauterine environment and breast cancer risk in women: A population-based study
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DOI：
10.1093/jnci/89.1.71
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发表时间：
1997-01-01
影响因子：
10.3
通讯作者：
Trichopoulos, D
中科院分区：
文献类型：
--
作者：
Ekbom, A;Hsieh, CC;Trichopoulos, D
背景:女性乳腺癌的既定危险因素，包括未生育、第一胎年龄、月经初潮年龄和绝经年龄，并不能充分解释这种癌症的发生模式，因此，需要考虑其他因素，以提高我们对乳腺癌病因的理解。从动物和人类获得的证据表明，围产期可能特别重要。我们早期的研究，基于本调查的子样本，提示，与妊娠期雌激素水平呈正相关的因素与乳腺癌风险呈正相关，然而，相关置信区间（ci）普遍较宽，表明数据存在相当大的差异。我们研究了大量的乳腺癌病例患者，并评估了几个与乳腺癌风险相关的围产期变量，这些变量包括一些以前没有研究过的变量，如胎龄和新生儿黄疸，我们还研究了双胞胎成员作为预测变量和乳腺癌死亡，除了乳腺癌的发生，作为替代结果变量。1874年至1961年期间，瑞典五家不同医院的所有分娩记录被用来确定一个大的妇女队列，该队列中的乳腺癌病例是通过1958年至1994年国家癌症登记处或乌普萨拉地区癌症登记处确定的。在一项嵌套在队列中的病例对照研究中，我们从1068例乳腺癌发病妇女和2727例与病例患者出生日期相匹配的对照受试者的出生记录中提取数据，我们通过条件logistic回归对数据进行建模，所有P值均来自双侧统计检验，结果：我们发现母亲患有妊娠毒血症的妇女患乳腺癌的风险显著降低(优势比[OR] = 0.41；95% CI = 0.22-0.79)和新生儿黄疸（OR = 2.16; 95% CI = 1.27-3.67）或妊娠33周前出生的妇女（OR = 3.96; 95% CI = 1.45-10.81）的风险过高。与单胎相比，异卵双胞胎患乳腺癌的风险增加，尽管这种增加没有统计学意义(OR = 1.72；95% CI = 0.92-3.20)，这些数据中没有证据表明乳腺癌风险与出生尺寸指标（即出生时体重、体长和胎盘重量）有统计学显著或实质性的关联。由于妊娠毒血症与雌激素水平低、新生儿黄疸、严重早产和雌激素水平高的异卵双胞胎有关，我们的研究结果表明，雌激素和其他已知影响成人乳腺癌风险的激素因素，也可能在宫内期发挥关键作用。
Background: The established risk factors for female breast cancer, including nulliparity, age at first birth, age at menarche, and age at menopause, do not adequately explain the occurrence pattern of this cancer, Therefore, additional factors need to be considered to advance our understanding of the causes of breast cancer, Evidence obtained from animals and humans indicates that the perinatal period may be particularly important, Our earlier studies, based on a subsample of the present investigation, suggested that factors thought to be positively associated with estrogen levels during pregnancy are positively associated with breast cancer risk, However, the associated confidence intervals (CIs) were generally wide, indicating considerable variability in the data, Purpose: We studied a large number of incident breast cancer case patients and evaluated several perinatal variables in relation to breast cancer risk, These variables included some not previously studied, such as gestational age and neonatal jaundice, We also investigated twin membership as a predictor variable and death from breast cancer, in addition to occurrence of breast cancer, as an alternative outcome variable, Methods: Birth records for all deliveries at five different hospitals in Sweden during the period from 1874 through 1961 were used to define a large cohort of women, Incident case patients with breast cancer in this cohort were ascertained through the National Cancer Registry or the Uppsala Regional Cancer Registry from 1958 through 1994. In a case-control study nested in the cohort, we abstracted data from birth records on 1068 women with incident breast cancer and on 2727 control subjects individually matched to the case patients on date of birth, We modeled the data through conditional logistic regression, All P values were derived from two-sided statistical tests, Results: We found a markedly reduced risk for breast cancer in women whose mothers had pregnancy toxemia (odds ratio [OR] = 0.41; 95% CI = 0.22-0.79) and an excess risk on women who had neonatal jaundice (OR = 2.16; 95% CI = 1.27-3.67) or who were born before 33 weeks of gestation (OR = 3.96; 95% CI = 1.45-10.81), Compared with the risk for breast cancer in the singleton, the risk for breast cancer in dizygotic twins was increased, although this increase was not statistically significant (OR = 1.72; 95% CI = 0.92-3.20), There was no evidence in these data for a statistically significant or substantial association of breast cancer risk with birth size indicators (i.e., weight and length at birth and placental weight), Conclusion and Implications: Because pregnancy toxemia is associated with low levels of estrogens and neonatal jaundice, severe prematurity, and dizygotic twins with high levels of estrogens, our findings suggest that estrogens and other hormonal factors, known to influence breast cancer risk in the adult, may also play a critical role during the intrauterine period.