Diet and Breast Density over Time in US Chinese Women

描述（由申请人提供）：移民到美国后，中国女性经历了乳腺癌风险增加的过渡。了解在外国出生的美籍华人女性生活方式的改变，有助于我们理解文化适应相关因素，尤其是成年后的文化适应因素，如何影响乳腺癌风险。在一项为期三年的纵向研究（1 R01 CA106606-01A2）中，我们对一组新移民的华裔美国女性进行了研究，研究了与文化适应相关的饮食变化与乳腺密度变化之间的关系。由于乳腺密度与乳腺癌风险密切相关，因此在流行病学研究中，通过密度面积和乳房照相显示致密外观的总乳房面积的百分比来测量的乳腺密度代表了乳腺癌风险的有用标记。在这里，我们建议考虑遗传因素，以研究以生活事件和异文化压力源为代表的社会心理压力可能与炎症相关基因相互作用以增加乳腺密度的机制。越来越多的证据表明，慢性炎症是癌症的一个重要危险因素。对某些人来说，炎症反应加剧的易感性也可能是乳腺癌遗传倾向的基础。炎症是乳腺癌风险的一个预测因素，因为预防策略可以针对炎症标志物以及已知的增加炎症标志物水平的因素，如社会心理压力。虽然心理社会压力在乳腺癌发展中的作用仍有争议，但先前的研究并未考虑遗传因素的潜在调节作用。研究压力的作用及其与遗传特征的相互作用可能对中国移民特别有用，因为他们在文化适应过程中经历了大量的文化和社会失衡。拟议的修订将：(1)在父母研究的435名参与者中检查压力，炎症标志物和乳腺密度之间的关联，以及(2)评估候选促炎基因与社会心理压力源之间的潜在相互作用。研究参与者为中国女性，绝经前/围绝经期，乳房x光检查年龄，在美国居住<=20年。父母研究的数据收集包括问卷调查，血清和DNA样本，以及乳房x光检查的乳腺密度测量值。社会心理压力源使用生活经验调查和迁移-文化适应压力源量表进行测量。我们建议使用这些可用的样本和数据进行：血清肿瘤坏死因子受体2 （TNFR2）、白细胞介素6 （IL6）、白细胞介素1 β、c反应蛋白（CRP）和纤维蛋白原的检测；5个候选促炎基因（tnf - α、il - 6、il - 1 β、CRP和β -纤维蛋白原）中选定的单核苷酸多态性和单倍型标记snp的基因分型；以及统计分析来评估压力、炎症标记物、基因多态性和乳腺密度之间的关联和相互作用。公共卫生相关性：拟议的项目将采用跨学科方法，结合乳腺癌流行病学、遗传流行病学和心理神经免疫学方面的专业知识，为社会心理和遗传因素之间的相互作用对乳腺密度的影响以及因此对乳腺癌风险的影响提供新的见解。有关显著相互作用的发现将被纳入已经为母体研究计划的统计分析中，并将为未来的分析提供信息，以确定研究样本中与文化相关的乳房密度预测因素。在更广泛的层面上，研究结果可以用于制定有效的预防策略，包括利用乳腺密度作为临床前结果的化学预防和减压计划，以及针对发现的增加乳腺癌风险的新基因型进行干预的遗传风险确定。

DESCRIPTION (provided by applicant): Upon migration to the US, Chinese women undergo a transition to increased risk for breast cancer. An understanding of lifestyle changes that occur in foreign-born, US Chinese women could contribute to our understanding of how acculturation-related factors, particularly in adulthood, affect breast cancer risk. In a three-year longitudinal study (1 R01 CA106606-01A2), we are examining the association between acculturation-related dietary changes and breast density changes in a unique cohort of recently immigrated, US Chinese women. Because of its strong association with breast cancer risk, breast density, as measured by both the area of density and the percentage of total breast area with a mammographically dense appearance, represents a useful marker for breast cancer risk in epidemiologic studies. Here, we propose to include a consideration of genetic factors in order to investigate a mechanism by which psychosocial stress, as represented by life event and acculturative stressors, might interact with inflammation-related genes to increase breast density. Increasing evidence suggests that chronic inflammation is an important risk factor for cancer. Predisposition to a heightened inflammatory response may also underlie genetic tendencies towards breast cancer in some individuals. Inflammation is of interest as a predictor of breast cancer risk because preventive strategies could target inflammatory markers as well as factors known to increase inflammatory marker levels, such as psychosocial stress. While the role of psychosocial stress in breast cancer development remains controversial, previous studies did not consider the potential moderating effect of genetic factors. Studies addressing the role of stress and its interaction with genetic characteristics may be especially informative within Chinese immigrants because they experience substantial cultural and social disequilibration during the acculturation process. The proposed revision will: (1) examine associations among stress, inflammatory markers, and breast density among the 435 participants in the parent study, and (2) evaluate potential interaction between candidate pro-inflammatory genes and psychosocial stressors. Study participants are Chinese, pre-/peri-menopausal, of mammography screening age, with US residence <=20 years. Data collection for the parent study includes questionnaires, serum and DNA samples, and breast density measurements from screening mammograms. Psychosocial stressors are measured using the Life Experiences Survey and the Migration-Acculturation Stressor Scale. We propose to use these available samples and data to conduct: serum assays for tumor necrosis factor receptor 2 (TNFR2), interleukin-6 (IL6), IL1beta, c-reactive protein (CRP), and fibrinogen; genotyping for selected single nucleotide polymorphisms and haplotype tagging SNPs in five candidate pro-inflammatory genes (TNF-alpha, IL6, IL1beta, CRP, and beta-fibrinogen); and statistical analyses to evaluate associations and interactions among stress, inflammatory markers and gene polymorphisms, and breast density. PUBLIC HEALTH RELEVANCE: The proposed project will use a transdisciplinary approach, with expertise in breast cancer epidemiology, genetic epidemiology, and psychoneuroimmunology, to offer new insight into the effects of interactions between psychosocial and genetic factors on breast density and, hence, breast cancer risk. Findings regarding significant interactions will be incorporated into statistical analyses already planned for the parent study, and will inform future analyses to identify acculturation-related predictors of breast density in the study sample. On a broader level, findings can be used towards developing effective preventive strategies, including chemoprevention and stress reduction programs utilizing breast density as a pre-clinical outcome, and genetic risk determination with interventions targeted at new genotypes found to increase breast cancer risk.