Project Summary My long-term goal is to become an independent researcher in the epidemiology of health effects of alcohol, and particularly its role in cancer. I am proposing this K01 Mentored Research Scientist Development Award to fulfill a series of training objectives which build upon my prior skills, but also expand my skills in ways which are essential to accomplishing my long-term goal. My training goals for this award are to: (1) develop a solid foundation in the use and interpretation of genetic data, with a focus on gene-environment interactions; (2) develop an understanding of the pathophysiology and treatments for breast cancer (BC) to assess and characterize cancer outcomes in epidemiologic studies; and (3) develop expertise in the design, conduct, and analysis of randomized clinical trials. To achieve my training objectives, I have assembled a comprehensive and complementary mentorship team with expertise in genetics, alcohol, sex hormones, BC and clinical trials. I will also participate in additional activities to further support my career development including coursework, lab meetings, training in the responsible conduct of research, grant writing, and presenting research at professional conferences. I will apply my training to conduct studies that explore whether there are factors that modify the association between alcohol and BC. There is consistent evidence of higher BC risk associated with daily alcohol intake, even within the recommended limit of up to one drink per day. However, important gaps in knowledge remain about whether there are factors that modify the association between alcohol and BC. This application will leverage existing data to study BC risk among women followed in epidemiological cohorts to test novel scientific questions about gene-environment interactions, using a candidate gene approach and a hypothesis-free genome-wide approach to identifying potential modifiers. In addition, the proposed training award will support an 8-week pilot crossover trial of 20 BC survivors who report that they regularly consume at least one alcoholic beverage per week and are currently prescribed aromatase inhibitor therapy. This trial will utilize the experienced clinical research center and large number of BC survivors receiving treatment at the institutions involved in this training award to generate pilot data that may inform a larger trial about the effects of alcohol on BC treatment. The training, mentorship, research experience, and opportunity to collect pilot data in this K01 award will allow me to achieve my long-term career goal of becoming an independent research in the epidemiology of health effects of alcohol and particularly its role in cancer.

Project Narrative Each 10 g (~1 drink) increase in daily alcohol intake has been associated with a ~10% higher risk of breast cancer incidence, the most common cancer in women, and some women may be at a particularly high risk of developing breast cancer due to alcohol intake. This application will leverage existing data on women followed in epidemiological cohorts to test novel scientific questions about gene-environment interactions, exploring previously identified SNPs that may modify the association between alcohol intake and breast cancer incidence, and using a hypothesis-free genome-wide approach to identify SNPs that may modify the association between alcohol intake and sex hormone levels. The application will also support a pilot randomized crossover trial among breast cancer survivors who consume at least one drink per week to examine whether alcohol intake affects sex hormone levels among women receiving aromatase inhibitor therapy.