Abstract PO-216: Circulating 27-hydroxycholesterol is associated with decreased breast cancer risk: The Multiethnic Cohort Study

Abstract

Abstract Background: Obesity is one of the most significant risk factors for breast cancer among postmenopausal women. Body fat distribution varies across racial/ethnic groups, which may partially explain the differences in breast cancer incidence across race/ethnicity. Laboratory studies have indicated that a cholesterol metabolite, 27-hydroxycholesterol (27HC), is an endogenous selective estrogen receptor modulator (SERM) and may represent an important obesity-related mechanism in breast cancer etiology. However, epidemiologic evidence for the role of 27HC in breast cancer risk is lacking, particularly in multiethnic populations. Methods: In a nested case-control study of 1,472 cases and 1.472 matched controls within the Multiethnic Cohort Study (MEC), we examined the association of circulating 27HC and lipids with breast cancer risk among African American, Japanese American, Native Hawaiian, Latino, and non-Latino White females. We conducted multivariable conditional logistic regression to assess associations of pre-diagnostic 27HC and lipids (modeled continuously on the log scale) with postmenopausal breast cancer risk adjusting for age at blood draw. Race/ethnicity stratified analyses were also conducted to assess differences in associations across racial/ethnic groups. Results: Among all females, higher levels of circulating 27HC were associated with a reduced risk of breast cancer (OR per log ng/ml: 0.71; 95% confidence interval (CI): 0.51, 0.99). Analyses stratified by race/ethnicity indicate that this association was driven by the Latino (OR: 0.39; 95% CI: 0.16, 0.93) and Japanese American (OR: 0.62; 95% CI: 0.35, 1.08) groups. Inverse associations were also observed with high-density lipoprotein and total cholesterol levels, while low-density lipoprotein levels were positively associated with breast cancer risk among all females. Conclusions: Ours is the first U.S. study to report a protective association between circulating 27HC and breast cancer risk in a multiethnic population. Interestingly, parallel analyses of a sub-cohort of healthy females in the MEC indicate inverse associations of total fat mass and percent subcutaneous fat assessed by dual X-ray absorptiometry and abdominal magnetic resonance imaging, respectively, with circulating 27HC. Ongoing analyses are evaluating joint associations of circulating 27HC, lipids, estrogens, and androgen levels with breast cancer risk. Results from this study will improve our understanding of racial/ethnic differences in breast cancer risk in relation to body fat distribution and inform prevention strategies for postmenopausal breast cancer. Citation Format: Mindy C DeRouen, Juan Yang, Yuqing li, Adrian A. Franke, Anne Tome, Kami White, Brenda Hernandez, Yurii Shvestov, V. Wendy Setiawan, Anna H. Wu, Lynne Wilkens, Loic Le Marchand, Lenora WM Loo, Iona Cheng. Circulating 27-hydroxycholesterol is associated with decreased breast cancer risk: The Multiethnic Cohort Study [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-216.