Early Life Exposures and Subsequent Cancer Risk

生命早期的暴露和随后的癌症风险

• 批准号: 10918982
• 负责人: Gretchen Gierach
• 金额: $ 102.87万
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10918982
• 关键词: AFP gene; Adult; Adult Children; Androstenedione; Animal Model; Behavioral; Biological Assay; Birth; Birth Weight; Blood specimen; Body of uterus; Boston; Breast Cancer Risk Factor; Categories; China; Cohort Studies; Collaborations; Collection; Contractor; Data; Daughter; Dehydroepiandrosterone Sulfate; Diethylstilbestrol; Disease; Electronics; Estradiol; Estriol; Estrogens; Estrone; Europe; Exposure to; Female; Functional disorder; Gestational Age; Health Sciences; Hormones; Immune system; Insulin-Like Growth Factor Binding Protein 3; Label; Laboratories; Link; Louisiana; Malignant Neoplasms; Maternal Age; Medical Records; Medical center; Mothers; National Institute of Child Health and Human Development; Pathology Report; Perinatal; Pharmaceutical Preparations; Phase; Placenta; Pre-Eclampsia; Pregnancy; Pregnant Women; Premature Birth; Preneoplastic Conditions; Prevention; Progesterone; Prolactin; Questionnaires; Reporting; Son; Spontaneous abortion; Standardization; Testosterone; Twin Multiple Birth; Umbilical Cord Blood; Umbilical cord structure; Universities; Uterine Diseases; Work; cancer risk; cohort; dehydroepiandrosterone; early life exposure; follow-up; high risk; in utero; male; medical schools; member; neoplasm registry; offspring; prenatal exposure; prostate cancer risk; reproductive; vaginal clear cell adenocarcinoma

00020 - Diethylstilbestrol (DES), a drug first synthesized in 1938, was administered to several million pregnant women in the U.S. and Europe for the prevention of spontaneous abortion and premature delivery. In 1971, Herbst reported a strong association between DES use in pregnancy and the occurrence of vaginal clear cell adenocarcinoma (CCA) in exposed female offspring. Animal models have demonstrated a range of DES effects on offspring exposed in utero, including reproductive dysfunction, immune system changes, behavioral and sexual abnormalities, and increases in various reproductive cancer in males and females. NCI, in collaboration with five field centers, reassembled previously studied cohorts of DES-exposed and unexposed mothers, daughters and sons, and identified subjects with documented exposure status who had not been studied previously, through familial links within the cohorts. Standardized baseline questionnaires were mailed to cohort members to ascertain the risk of cancer and other disorders. Pathology reports were collected for reported cancers and preneoplastic conditions. Theree separate phases of follow-up have been conducted. The purpose of this study is to continue the follow-up, by means of mailed questionnaires and medical record collection, which was begun during the the first phase of the study. Concern has arisen that DES-exposed daughters may be at higher risk of breast cancer. Exposure to high levels of endogenous estrogen in utero has been hypothesized to increase the risk of breast cancer and DESis a potent estrogen. Cacner risk in the sons will also continure to be assessed, especailly for increased risks of prostate cancer. since the offspring who were exposed to DES in utero are currently reaching their late forties, when cancer rates begin to rise, it is important to continue the follow-up of these cohorts to determine if there are long-term increases in cancer risk. 10039 - The proposed study involves collecting maternal and cord blood samples from monochorionic twin, dichorionic twin and singleton pregnancies of similar gestational age to quantify differences in concentrations of several hormones and other pregnancy products including estriol, estradiol, estrone, testosterone, androstenedione, dehydroepiandrosterone (DHEA), DHEA-sulfate, progesterone, AFP, prolactin, IGF and IGF-binding protein 3. Data from medical records and pathology reports will be abstracted to provide information on the mother, baby, pregnancy and placenta. The work will be done at Dartmouth Hitchcock Medical Center, Dartmouth Medical School. Blood samples labeled with a unique ID number only will be sent to Bioreliance, NCI's contractor, for preperation and shipment to the laboratory that will perform the hormone assays. NCI will receive the abstracted data in electronic form. no personal identifying information will be received by NCI or its contractor. The study has been approved by Dartmouth Medical School. 10041 - The Norwegian birth and cancer registries will be used to investigate the association of several pregnancy and perinatal factors and risk of cancer in adult offspring. 10032 - Collaboration with NICHD on a study of preeclampsia conducted at Louisiana State University Health Sciences Center. Blood samples are being collected from mothers and from umbilical cords with and without preeclampsia. The relationship of pregnancy hormone levels and preeclampsia will be analyzed. 01132 - In this study using data from a cohort study of preeclamptic and uncomplicated pregnancies at the University of Pittsburgh, we are analyzing maternal and cord blood samples from preeclamptic and normal pregnancies of similar gestational age to quantify differences in levels of various hormones. We will evaluate associations of several maternal, perinatal and pregnancy factors, such as maternal age and birth weight, with hormone levels in normal pregnancies. In addition, we will determine how well maternal levels represent levels in cord blood. 00043 - Umbilical cord blood samples were collected from 75 pregnancies in Boston, MA and 175 in Shanghai, China. Pregnancy hormone concentrations will be determined and correlated with putative breast cancer risk factors.

1938年首次合成的药物己烯雌酚（DES）被用于美国和欧洲数百万孕妇，以预防自然流产和早产。1971年，Herbst报告了妊娠期使用DES与暴露雌性后代发生阴道透明细胞腺癌（CCA）之间的强相关性。动物模型已经证明DES对子宫内暴露的后代的一系列影响，包括生殖功能障碍，免疫系统变化，行为和性异常，以及男性和女性各种生殖癌症的增加。NCI与五个现场中心合作，重新组装了以前研究过的DES暴露和未暴露的母亲，女儿和儿子的队列，并通过队列内的家庭联系确定了以前未研究过的记录暴露状态的受试者。标准化的基线问卷被邮寄给队列成员，以确定癌症和其他疾病的风险。收集了报告的癌症和肿瘤前疾病的病理学报告。已经进行了三个不同阶段的后续行动。本研究的目的是通过邮寄问卷和收集病历的方式继续随访，这是在研究的第一阶段开始的。人们担心，接触DES的女儿患乳腺癌的风险可能更高。在子宫内暴露于高水平的内源性雌激素被认为会增加患乳腺癌的风险，而DES是一种有效的雌激素。儿子患前列腺癌风险也将继续评估，特别是前列腺癌风险增加。由于在子宫内暴露于DES的后代目前已接近40岁，此时癌症发病率开始上升，因此继续随访这些群体以确定癌症风险是否长期增加是重要的。10039 -拟定的研究包括从单绒毛膜双胎、双绒毛膜双胎和相似胎龄的单胎妊娠中采集母体和脐带血样本，以量化几种激素和其他妊娠产物（包括雌三醇、雌二醇、雌酮、睾酮、雄烯二酮、脱氢表雄酮（DHEA）、硫酸脱氢表雄酮、孕酮、AFP、催乳素、IGF和IGF结合蛋白3）浓度的差异。将从病历和病理学报告中提取数据，以提供有关母亲、婴儿、妊娠和胎盘的信息。这项工作将在达特茅斯医学院的达特茅斯希区柯克医疗中心完成。仅标有唯一ID号的血液样本将被送往NCI的承包商Bioreliance进行准备并运送到将进行激素测定的实验室。NCI将以电子形式收到摘要数据。NCI或其承包商不会收到任何个人身份信息。这项研究已经得到了达特茅斯医学院的批准。10041 -挪威出生和癌症登记将用于调查几种妊娠和围产期因素与成年后代癌症风险之间的关系。10032 -与NICHD合作在路易斯安那州立大学健康科学中心进行先兆子痫研究。正在从患有和不患有先兆子痫的母亲和脐带中收集血液样本。分析妊娠期激素水平与子痫前期的关系。01132 -在这项研究中，使用匹兹堡大学先兆子痫和无并发症妊娠的队列研究数据，我们分析了相似胎龄的先兆子痫和正常妊娠的母体和脐带血样本，以量化各种激素水平的差异。我们将评估几个产妇，围产期和怀孕因素，如产妇年龄和出生体重，与正常妊娠激素水平的关联。此外，我们将确定母体水平代表脐带血水平的程度。00043 -从马萨诸塞州波士顿的75名孕妇和中国上海的175名孕妇收集脐带血样本。将测定妊娠激素浓度，并将其与推定的乳腺癌风险因素相关联。

项目成果

A migrant study of pubertal timing and tempo in British-Bangladeshi girls at varying risk for breast cancer.

• DOI: 10.1186/s13058-014-0469-8
• 发表时间: 2014-11-15
• 期刊: Breast cancer research : BCR
• 作者: Houghton LC;Cooper GD;Bentley GR;Booth M;Chowdhury OA;Troisi R;Ziegler RG;Hoover RN;Katki HA
• 通讯作者: Katki HA

Blood pressure augmentation and maternal circulating concentrations of angiogenic factors at delivery in preeclamptic and uncomplicated pregnancies.

• DOI: 10.1016/j.ajog.2008.06.030
• 发表时间: 2008-12
• 期刊: AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
• 影响因子: 9.8
• 作者: Troisi, Rebecca;Braekke, Kristin;Harsem, Nina Kittelsen;Hyer, Marianne;Hoover, Robert N.;Staff, Anne Cathrine
• 通讯作者: Staff, Anne Cathrine

Pregnancy weight gain is not associated with maternal or mixed umbilical cord estrogen and androgen concentrations.

• DOI: 10.1007/s10552-008-9235-5
• 发表时间: 2009-03
• 期刊: CANCER CAUSES & CONTROL
• 影响因子: 2.3
• 作者: Faupel-Badger, Jessica M.;Hoover, Robert N.;Potischman, Nancy;Roberts, James M.;Troisi, Rebecca
• 通讯作者: Troisi, Rebecca

Associations of pregnancy characteristics with maternal and cord steroid hormones, angiogenic factors, and insulin-like growth factor axis.

• DOI: 10.1007/s10552-011-9835-3
• 发表时间: 2011-11
• 期刊: CANCER CAUSES & CONTROL
• 影响因子: 2.3
• 作者: Faupel-Badger, Jessica M.;Wang, Yuping;Karumanchi, S. Ananth;Stanczyk, Frank;Pollak, Michael;McElrath, Thomas;Hoover, Robert N.;Troisi, Rebecca
• 通讯作者: Troisi, Rebecca

Preterm delivery is associated with an increased risk of epithelial ovarian cancer among parous women.

• DOI: 10.1002/ijc.31581
• 发表时间: 2018-10-15
• 期刊: International journal of cancer
• 影响因子: 6.4
• 作者: Sköld C;Bjørge T;Ekbom A;Engeland A;Gissler M;Grotmol T;Madanat-Harjuoja L;Gulbech Ording A;Stephansson O;Trabert B;Tretli S;Troisi R;Sørensen HT;Glimelius I
• 通讯作者: Glimelius I