Anti-Mullerian Hormone Genes and Breast Cancer Risk

抗苗勒氏管激素基因与乳腺癌风险

• 批准号: 7897148
• 负责人: JOANNE F DORGAN
• 金额: $ 8.73万
• 依托单位: FOX CHASE CANCER CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7897148
• 关键词: ACVR1 gene; AMHR2 gene; Adrenal Glands; Androgens; Area; Cancer Etiology; Case-Control Studies; Complex; Contraceptive Agents; DNA; Data; Detection; Estrogen Receptor Status; Estrogen Receptors; Estrogens; Evaluation; Frequencies; Genes; Genetic; Genetic Polymorphism; Genotype; Goals; Haplotypes; Hormonal; Hormone replacement therapy; Lead; Logistic Regressions; Mammary Neoplasms; Menopausal Status; Menopause; Ovarian; Ovarian Steroid Hormone; Ovary; Peripheral; Philadelphia; Process; Public Health; Questionnaires; Resources; Risk; Role; Screening procedure; Serum; Source; Steroid biosynthesis; Time; Variant; Woman; abstracting; base; cancer risk; experience; folliculogenesis; insight; malignant breast neoplasm; mullerian-inhibiting hormone; novel; population based; public health relevance; receptor; therapy development; tumor

DESCRIPTION (provided by applicant): ABSTRACT A pivotal role for estrogens in breast cancer etiology has been known for decades. In women, the source of estrogens varies by menopausal status. The ovaries are the predominant source before menopause and peripheral conversion of androgens that are secreted by the ovaries and adrenals is the predominant source after menopause. Ovarian steroid hormone synthesis is complex and is intimately related to the underlying process of ovarian folliculogenesis. Anti-Mullerian Hormone (AMH) is a key regulator of ovarian folliculogenesis, and we recently observed a highly significant increased risk of breast cancer associated with elevated serum AMH levels. Genetics is a major determinant of ovarian function. The primary specific aim of the proposed study is to determine if putative functional polymorphisms and haplotype tagging SNPs (htSNPs) in the AMH gene and genes that encode its type 1 (ACVR1) and type 2 receptors (AMHR2) are associated with breast cancer risk. The study will be conducted using resources previously collected in the Women's Insights and Shared Experiences Study (WISE), which was a population-based case-control study conducted in the Philadelphia area. WISE included 878 cases and 1409 frequency matched controls who provided questionnaire data and DNA. Genotyping will be conducted on the Sequenom platform. The association of AMH, ACVR1 and AMHR2 genotype with breast cancer risk will be evaluated primarily using unconditional logistic regression. PUBLIC HEALTH RELEVANCE: RELEVANCE TO PUBLIC HEALTH We recently observed a highly significant increased risk of breast cancer in women with elevated serum levels of anti-mullerian hormone (AMH). Identification of the underlying genetic basis for this association could substantially increase our understanding of breast cancer etiology. Ultimately, results could lead to identification of women at increased risk of breast cancer, advances in screening for detection of women at increased risk and development of interventions to lower risk in susceptible women.

描述（由申请人提供）：摘要几十年来，人们已经知道雌激素在乳腺癌病因学中的关键作用。对于女性来说，雌激素的来源因更年期状况而异。卵巢是绝经前的主要来源，绝经后卵巢和肾上腺分泌的雄激素的外周转化是主要来源。卵巢类固醇激素的合成非常复杂，与卵巢卵泡发生的基本过程密切相关。抗苗勒氏管激素 (AMH) 是卵巢卵泡生成的关键调节因子，我们最近观察到与血清 AMH 水平升高相关的乳腺癌风险显着增加。遗传是卵巢功能的主要决定因素。拟议研究的主要具体目的是确定 AMH 基因以及编码其 1 型 (ACVR1) 和 2 型受体 (AMHR2) 的基因中推定的功能多态性和单倍型标记 SNP (htSNP) 是否与乳腺癌风险相关。该研究将使用之前在女性见解和共享经验研究 (WISE) 中收集的资源进行，该研究是在费城地区进行的一项基于人群的病例对照研究。 WISE 纳入了 878 例病例和 1409 名频率匹配的对照，他们提供了问卷数据和 DNA。基因分型将在 Sequenom 平台上进行。 AMH、ACVR1 和 AMHR2 基因型与乳腺癌风险的关联将主要使用非条件逻辑回归进行评估。 公共卫生相关性：我们最近观察到血清抗苗勒管激素 (AMH) 水平升高的女性患乳腺癌的风险显着增加。确定这种关联的潜在遗传基础可以大大增加我们对乳腺癌病因学的理解。最终，研究结果可能会导致识别乳腺癌风险增加的女性，在筛查检测风险增加的女性方面取得进展，并制定干预措施以降低易感女性的风险。