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.
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.
