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.

摘要：雌激素在乳腺癌病因学中的关键作用已经知道了几十年。在女性中，雌激素的来源因绝经状态而异。卵巢是绝经前雄激素的主要来源，卵巢和肾上腺分泌的外周转化是绝经后雄激素的主要来源。卵巢类固醇激素的合成是复杂的，与卵巢卵泡发生的潜在过程密切相关。抗苗勒管激素（AMH）是卵巢卵泡发生的关键调节因子，我们最近观察到血清AMH水平升高与乳腺癌风险显著增加相关。遗传是卵巢功能的主要决定因素。该研究的主要目的是确定AMH基因和编码其1型受体（ACVR1）和2型受体（AMHR2）的基因中假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。该研究将使用先前在女性见解和共享经验研究（WISE）中收集的资源进行，这是一项在费城地区进行的基于人群的病例对照研究。WISE纳入了878例病例和1409例频率匹配的对照组，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系将主要采用无条件logistic回归进行评估。