Abstract A65: Association between genetic ancestry and breast cancer tumor characteristics among admixed Latina and Native Hawaiian populations: The Multiethnic Cohort.

Introduction: Breast cancer incidence and mortality rates vary dramatically across racial/ethnic groups. For instance, the incidence rate of breast cancer among Native Hawaiians is higher than that of European Americans with lower incidence of disease seen among Latinas. However, both Latinas and Native Hawaiians are more likely to be diagnosed with later stage breast cancer, and whether genetic ancestry contributes to tumor characteristics remains unclear. Therefore, we investigated the association between genetic ancestry and breast cancer tumor characteristics among two admixed populations, Latinas and Native Hawaiians, within the Multiethnic Cohort study (MEC). Methods: We used the Taqman Open Array platform to genotype 93 ancestral informative markers (AIMs), which could assess major continental ancestry, in 22,932 self-reported African American, European American, Japanese American, Latino, and Native Hawaiian MEC participants as part of an on-going study. The STRUCTURE software was used in the available ancestral populations (HapMap CEU, JPT and YRI and American Indians from HGDP) to determine and enhance the accuracy of the percent ancestry estimation for each individual. For this study, 651 Latina and Native Hawaiian breast cancer cases from our nested case-control study were examined. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the associations of genetic ancestry with breast cancer stage, cell differentiation, and hormone receptor information. The models were adjusted for age at cancer diagnosis, mammographic screening, family history of breast cancer, education, age at menarche, age at first child birth, number of children, menopausal status, oral contraceptive use, hormone replacement therapy use and body mass index. Results: Among Native Hawaiian (n=193) breast cancer cases, a 10% increase in Native Hawaiian ancestry was positively associated with advanced stage of disease (regional/metastastic) in comparison to localized disease (OR=1.18; 95% CI: 1.02-1.37). Among Latina breast cancer cases (n=410), a 10% increase in American Indian ancestry was inversely associated with advanced stage of disease (OR=0.91; 95% CI: 0.85-0.99); however, a suggestive positive association was found with poorer breast cancer cell differentiation (OR=1.08; 95% CI: 0.99-1.16). Among those with hormone receptor information, we did not detect an association between genetic ancestry and estrogen receptor negative (ER-) or progesterone receptor negative (PR-) status in Latinas. However, for Native Hawaiians, Hawaiian ancestry had a suggestive positive association with PR- status breast cancer (n=123; OR=1.22; 95% CI: 0.99-1.50), and East Asian Ancestry had a suggestive positive association with ER-/PR- status (n=109; OR=1.49; 95% CI: 0.98-2.26). Conclusion: Our findings suggest that genetic ancestry may contribute to breast cancer tumor characteristics among admixed populations. Citation Format: Sungshim L. Park, Hansong Wang, Christian P. Caberto, Maarit Tiirikainen, Lynne R. Wilkens, Laurence N. Kolonel, Brian E. Henderson, Christopher A. Haiman, Loic Le Marchand, Iona Cheng. Association between genetic ancestry and breast cancer tumor characteristics among admixed Latina and Native Hawaiian populations: The Multiethnic Cohort. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr A65.