Diet and Breast Density over Time in US Chinese Women

描述(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国华裔女性的生活方式变化，有助于我们理解与文化适应相关的因素，特别是成年后，如何影响乳腺癌风险。在一项为期三年的纵向研究中(1R01 CA106606-01A2)，我们在一个独特的新近移民的美籍华裔女性队列中，研究了与文化适应相关的饮食变化和乳房密度变化之间的关联。由于乳房密度与乳腺癌风险密切相关，因此在流行病学研究中，乳房密度是一种有用的乳腺癌风险标记物。在这里，我们建议包括遗传因素的考虑，以研究以生活事件和文化适应应激源为代表的心理社会应激可能与炎症相关基因相互作用以增加乳房密度的机制。越来越多的证据表明，慢性炎症是癌症的一个重要风险因素。对高度炎症反应的易感性也可能是一些人患乳腺癌的遗传倾向的基础。炎症是乳腺癌风险的预测指标，因为预防策略可以针对炎症标记物以及已知的增加炎症标记物水平的因素，如心理社会压力。虽然心理社会压力在乳腺癌发生中的作用仍然存在争议，但以前的研究没有考虑到遗传因素的潜在缓和作用。关于压力的作用及其与基因特征相互作用的研究可能对中国移民特别有用，因为他们在适应文化的过程中经历了严重的文化和社会失衡。拟议的修订将：(1)在母研究的435名参与者中检查压力、炎症标记物和乳房密度之间的关联，以及(2)评估候选促炎基因和心理社会应激源之间的潜在交互作用。研究参与者是中国人，绝经前/围绝经期，乳房X光检查年龄，在美国居住=20年。家长研究的数据收集包括问卷、血清和DNA样本，以及筛查乳房X光检查的乳房密度测量。采用《生活体验调查》和《移民-文化适应压力源量表》测量心理社会应激源。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)、白介素6(IL6)、白介素1β(IL1β)、C反应蛋白(CRP)和纤维蛋白原的检测；5个候选致炎基因(肿瘤坏死因子α、白介素6、白介素1β、C反应蛋白和β纤维蛋白原)中选定的单核苷酸多态和单倍型标记SNP的基因分型；以及评估应激、炎症标志物和基因多态与乳房密度之间的关联和相互作用的统计分析。公共卫生相关性：拟议的项目将使用跨学科的方法，拥有乳腺癌流行病学、遗传流行病学和心理神经免疫学的专业知识，以提供新的见解，了解心理社会和遗传因素之间的相互作用对乳房密度的影响，从而影响乳腺癌的风险。关于显著交互作用的结果将被纳入已为父母研究计划的统计分析中，并将在未来的分析中提供信息，以确定研究样本中与文化适应相关的乳房密度预测因素。在更广泛的层面上，研究结果可用于开发有效的预防策略，包括利用乳房密度作为临床前结果的化学预防和减压计划，以及针对被发现增加乳腺癌风险的新基因类型的干预措施来确定遗传风险。

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.