Evaluation of p53-MDM2 Ocogene Functionin Breast Cancer among Native Hawaiians


Loo_Photo1Breast cancer is the most common cancer among women in the United States. One in eight women will be diagnosed with invasive breast cancer in her lifetime. Despite improvements in survival rates, the disease remains the second leading cause of cancer death for women in the U.S.  The rates of breast cancer vary across racial/ethnic populations.  Based on the data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program (SEER), which provides information on national cancer statistics, Native Hawaiian women have the highest incidence and mortality rates of breast cancer in the nation, with mortality rates similar to African American women.  Despite an increase in the number of recent studies on breast cancer biology and prognostic factors on minority populations, there still remains a paucity of biological data on breast cancers from minority populations, particularly Native Hawaiians/Pacific Islanders.

Drs. Lenora Loo (Principal Investigator) and Jill Bargonetti (mentor and co-investigator) are working together to examine if there is an association between poor breast cancer survival in Native Hawaiian/Pacific Islander women and the presence of mutations in the tumor suppressor, p53, and overexpression of the p53 negative regulator, MDM2. Specifically, they intend to evaluate p53-MDM2 tumor suppressor inactivation and its downstream effects on the cholesterol synthesis pathway in these breast tumors.  Dr. Bargonetti (mentor and co-investigator) and colleagues found that the mevalonate pathway, the key pathway involved in cholesterol synthesis, is upregulated in breast tumors with mutant p53 and is associated with the disruption to mammary tissue architecture and poor breast cancer survival (Freed-Pastor WA et al. 2012. Cell 148:244-258).

Drs. Loo and Bargonetti will examine the association between the expression patterns of biomarker proteins (p53, MDM2, MDM2-C, and cholesterol synthesizing enzymes) in breast tumor tissue and survival for almost 400 breast cancer cases with over 15 years of follow-up.  These breast cancer cases were all diagnosed in Hawaii and include individuals of different race/ethnicities.  The team will evaluate racial/ethnic differences in biomarker expression and survival, with specific focus on breast cancers from Native Hawaiian/Pacific Islander women.  This study is possible because of the availability of the largest collection of clinically annotated archived breast tumor tissue from Native Hawaiian/Pacific Islander women through the Hawaii Tumor Registry Residual Tissue Repository program.  This pilot study is critical for evaluating these potential biomarkers and has the potential to have an important clinical translational impact for this understudied population.