Psychosocial modulation of mammary carcinogenesis

乳腺癌发生的社会心理调节

• 批准号: 7322247
• 负责人: Jason R Yee
• 金额: $ 3.44万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7322247
• 关键词: Adrenal Glands; Affect; Anthracenes; Apoptosis; Breast; Cancer Etiology; Carcinogens; Condition; Development; Disease; Ductal Carcinoma; Environment; Environmental Carcinogens; Estrous Cycle; Event; Exposure to; Female; Future; Genetic Predisposition to Disease; Genomic Instability; Germ-Line Mutation; Glucocorticoids; Goals; Growth; Growth and Development function; Health; Hormonal; Hormone Receptor; Individual Differences; Inherited; Life; Longevity; Malignant - descriptor; Malignant Neoplasms; Mammary Neoplasms; Mammary Tumorigenesis; Mammary gland; Measures; Mediating; Mutation; Neoplasm Metastasis; Noninfiltrating Intraductal Carcinoma; Ovarian; Ovarian hormone; Palpable; Phase; Population; Premalignant; Process; Psychosocial Factor; Puberty; Rate; Rattus; Regulation; Research; Risk; Risk Factors; Role; Social isolation; Social support; Stress; Temperament; Testing; Thinking; Time; Tumor Promotion; Week; Woman; anthracene; carcinogenesis; chemical carcinogen; critical developmental period; day; dimethylbenzanthracene; environmental stressor; hormone regulation; indexing; insight; malignant breast neoplasm; mammary epithelium; mortality; neoplastic cell; psychologic; psychosocial; response; social; social inequality; trait; tumor; tumor initiation; tumorigenesis

DESCRIPTION (provided by applicant): Breast cancer is the leading cause of cancer in women and only 10% of cases thought to be caused by inherited germline mutations, suggesting a strong role for the interaction between environmental stressors and genetic predisposition. The aim of this proposal is to characterize how breast carcinogenesis is modulated by psychological traits and social circumstances that cause stress over the life-span. In rats, fearful temperament, lack of reciprocal social support, and social isolation confer an increased risk for spontaneous tumorigenesis and early mortality. Greater than 40% of tumors are malignant ductal carcinomas or pre-malignant ductal carcinoma in situ (DCIS). It is hypothesized that the endogenous regulation of glucocorticoid release in response to stress partially mediates this effect by suppressing apoptosis in neoplastic cells. To determine which phases of the carcinogenic process are amenable to psychosocial modulation, female rats will be administered 7,12-dimethylbenz(a)anthracene (DMBA), a well- characterized chemical carcinogen known to initiate mammary tumorigenesis. A subset of rats will be sacrificed 8 days following DMBA administration, the start of a 2-week critical period for tumor promotion, to measure rates of apoptosis and proliferation in the mammary epithelium. Another subset will be maintained until 50% of the population has developed at least one reliably palpable mammary tumor. Standardized tumor initiation will reveal whether subsequent phases of the carcinogenic process can be modulated by psychological traits and social circumstances that predispose stress over the life-span. A second related study will examine the role of life-long psychosocial factors in mammary development. The degree to which developing mammary glands are exposed to pre-cyclic ovarian hormone dynamics is hypothesized to be a strong risk factor for mammary carcinogenesis. We will test whether psychological traits and social circumstances that cause life-long stress predispose a carcinogenic hormonal environment by (1) tracking the onset of estrous cycles and (2) characterizing mammary development from puberty to young adulthood. Together, these studies will offer new insights into the psychological and social regulation of breast cancer by testing whether psychosocial factors affect tumor development and growth, and do so through the endogenous regulation of hormones. As such, these studies will also allow an estimation of the proportion of the racial disparity in breast cancer that can be explained by social inequalities.

描述（由申请人提供）：乳腺癌是女性癌症的主要原因，只有10％的病例被认为是由遗传性种系突变引起的，这表明环境压力源与遗传倾向之间的相互作用起着重要作用。该提议的目的是表征乳腺癌发生如何通过心理特征和社会环境调节，这些特征和社会环境会导致生命中的压力。在大鼠中，令人恐惧的气质，缺乏相互的社会支持以及社会隔离赋予了自发性肿瘤发生和早期死亡的风险增加。超过40％的肿瘤是恶性导管癌或原位恶性导管癌（DCIS）。假设糖皮质激素释放的内源性调节响应于应力部分通过抑制肿瘤细胞的凋亡来部分介导这种作用。为了确定致癌过程的哪个阶段可以与社会心理调节相提并论，将雌性大鼠施用7,12-二甲基苯子（A）蒽（DMBA），蒽（DMBA），这是一种良好的化学性致癌物，已知可以启动乳腺肿瘤发生。 DMBA给药后8天，将为肿瘤促进的2周关键时期开始，以衡量乳腺上皮细胞中凋亡和增殖速率，将处死一部分大鼠。将维持另一个子集，直到50％的人口至少出现可靠的乳腺肿瘤。标准化的肿瘤起始将揭示致癌过程的随后阶段是否可以通过心理特征和社会环境来调节，而这种特征和社会环境使压力偏爱生命跨度。第二项相关研究将研究终身社会心理因素在乳腺发展中的作用。假设，发育中的乳腺暴露于前卵巢激素动力学的程度是乳腺癌发生的强大危险因素。我们将通过（1）跟踪发情循环的发作以及（2）表征从青春期到年轻成年的乳腺发育的特征，来测试引起终身压力的心理特征和社会环境会使致癌的激素环境易受致癌的荷尔蒙环境。这些研究将通过测试心理社会因素是否影响肿瘤的发展和生长，从而为乳腺癌的心理和社会调节提供新的见解，并通过对激素的内源性调节来做到这一点。因此，这些研究还可以估算乳腺癌中种族差异的比例，可以通过社会不平等来解释。