ASPO Abstracts
Examining the association between immune biomarkers and pubertal maturation
Category: Molecular Epidemiology & Environment
Conference Year: 2021
Abstract Body:
Purpose: Bidirectional communication between the immune and hormonal systems mediates pubertal timing and
thus, breast cancer risk. However, limited studies assess the associations between immune biomarkers and
pubertal maturation. We examined immune marker profile across the pubertal window and the association
between immune biomarkers and the age of onset of pubertal timing.
Methods: We used the multiethnic, multisite LEGACY girls' cohort (New York, Ontario, Pennsylvania, and Utah)
and examined a panel of 21 cytokines and chemokines (e.g., MIP1ß, TNFα) in a sub-cohort of 92 girls who had a
first available blood biospecimen prior to the age of onset of menses and had at least 2 blood biospecimens.
Median smoothed line and bean plot visualizations found potential trends in biomarker expression level by age.
Time-to-event (TTE) graphs described biomarker levels pre- and post- breast development as defined as Tanner
Stage 1 (T1) compared to T2 or higher. Using the corresponding measures from the first available biospecimen,
we generated a correlation matrix including the biomarker, age, and BMI for-age-percentile. Parametric Weibull
models assessed each biomarker and age of onset of breast development adjusted for age, BMI, and the
interactions for age*BMI and age*biomarker.
Results: The multiethnic cohort (70% non-Hispanic White, 18% Hispanic, 5% non-Hispanic Black, 3% Asian, and
3% other races/ethnicities) were on average age (standard deviation) 8.4 (1.4) and 89% were <85th BMI
percentile at the first available biospecimen. There were 257 observations with 23% of girls having 4 or more
observations. We observed an inverse trend between MIP1ß and TNFα and age. TNFα recapitulated this trend
upon visualization of the TTE graphs and further decreased after breast development. Overall, the immune
biomarkers were closely correlated to each other but were inversely associated with age and BMI-percentile.
Weibull models suggested TNFα was associated with a later age at breast development (Hazard Ratio 0.93 (95%
Confidence Interval 0.86, 1.00)).
Conclusion: Confirming previous studies, TNFα may be associated with the age of onset of breast development.
We will conduct quantile regression to confirm findings and replicate models for pubic hair development and
menarche.
Keywords: breast development, immune biomarker, pubertal timing