Anti-Mullerian Hormone Genes and Breast Cancer Risk

描述（由申请人提供）：摘要雌激素在乳腺癌病因学中的关键作用已被人们了解了几十年。在女性中，雌激素的来源因绝经状态而异。卵巢是绝经前的主要来源，而卵巢和肾上腺分泌的雄激素的外周转化是绝经后的主要来源。卵巢类固醇激素的合成是一个复杂的过程，与卵泡发生的基本过程密切相关。抗苗勒管激素（AMH）是卵巢卵泡发生的关键调节因子，我们最近观察到与血清AMH水平升高相关的乳腺癌风险显著增加。遗传是卵巢功能的主要决定因素。这项研究的主要目的是确定AMH基因和编码其1型（ACVR 1）和2型受体（AMHR 2）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。这项研究将使用以前在妇女的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包括878例病例和1409例频率匹配的对照，他们提供了问卷资料和DNA。将在Sequenom平台上进行基因分型。AMH、ACVR 1和AMHR 2基因型与乳腺癌风险的关联将主要使用非条件logistic回归进行评估。 公共卫生相关性：与公共卫生的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著增加。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，研究结果可能导致识别乳腺癌风险增加的妇女，在筛查检测风险增加的妇女方面取得进展，并制定干预措施，以降低易感妇女的风险。

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.