It has been assumed that minority populations have accelerated aging through the “wear and tear” on their bodies that result from chronic exposure to social adversity and unhealthy behaviors. Consistent with this assumption, research shows that Black women who have shorter telomere length (an indicator of more rapid cellular aging), are more likely to have earlier onset of breast cancer, more aggressive forms of breast tumors, and a shorter survival compared with Whites. In addition to telomere length, studies in the past decades have discovered multiple other molecular mechanisms contributing to accelerated biological aging, including cellular senescence. Cellular senescence is a stress response mechanism that will lead to replication arrest and complex changes in morphology, chromatin organization, and expression of typical protein biomarkers. p16INK4a mRNA serves as a potent biomarker of biological aging and physiologic reserve that may play a causal role in aging by promoting cellular senescence. In this study, we examined cross-sectional associations among social-demographics, lifestyle behaviors, tumor characteristics, and p16INK4a mRNA expression in peripheral blood leukocytes, among a cohort of 828 breast cancer patients aged 20 to 80 years (including 601 Whites and 227 Blacks), who were diagnosed with primary stage I to III breast cancer at M.D. Anderson Cancer Center from 2013 to 2018. p16INK4a mRNA expression levels were inversely correlated with age (ρ=-0.15, ρ<0.001). In the multivariate analysis, p16INK4a mRNA expression levels were significantly higher among Blacks than Whites (P<0.001). Then, we assessed the associations between p16INK4a mRNA expression levels with social-demographics and healthy behaviors at baseline. p16INK4a mRNA expression levels were higher among breast cancer cases currently smoking cigarettes (P=0.021), being physical inactive (P=0.014), having no college level of education (P=0.014), and having < $20,000 annual income (P=0.027), compared to their counterparts. The significant associations between p16INK4a mRNA expression with education and income were more evident among Blacks than Whites. Finally, we assessed the associations between p16INK4a mRNA expression levels with breast tumor characteristics at baseline, including estrogen receptor (ER) status, and tumor stage, grade, and size, as well as age of disease onset. Overall, no significant association was observed. However, when stratified by race, significant associations were observed for ER status and tumor grade among Blacks. Higher levels of p16INK4a mRNA expression were associated with increased odds of having ER negative (ER-) and poorly differentiated breast tumors (ER-: Odds Ratio (OR): 1.39, 95% Confidence Interval (CI): 1.12, 1.70; poorly differentiated: 1.23, 95%CI: 1.02, 1.48) among Blacks. In summary, our results support the notion that p16INK4a mRNA is a biological mechanism by which social demographics and health behaviors “get under the skin” to affect health.

Citation Format: Jie Shen, Renduo Song, Bernard Fuemmeler, Wong-Ho Chow, Hua Zhao. Social-demographics, health behaviors, and p16INK4a mRNA expression in White and Black breast cancer patients [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-158.