# Diurnal Variations in Salivary Concentrations of Pro-Tumorigenic Cytokines and Possible Effects of Psycho-Physiological Stress in Gynecologic Cancer Patients and Matched Healthy Controls

> **NIH NIH F31** · UNIVERSITY OF FLORIDA · 2021 · $41,244

## Abstract

PROJECT SUMMARY/ABSTRACT
The primary goal of the proposed study is to identify and compare the diurnal circadian pattern of salivary
concentrations of pro-tumorigenic and inflammatory cytokines, specifically interleukin-6 (IL-6) and interleukin-
1beta (IL-1β), in gynecologic oncology patients and age and race/ethnicity matched healthy controls. Healthy
controls are specifically conceptualized as individuals who do not have a history of cancer (i.e., non-cancer
control group). The proposed study further aims to examine the relationships between psycho-physiological
stress (i.e., subjective [perceived stress] and objective [salivary cortisol] measures of stress) and diurnal salivary
cytokine expression in these two groups. Mounting empirical evidence provides support for possible pro-
tumorigenic effects of inflammatory and immune responses, psychological stress, and dysregulation of circadian
clock gene expression that may ultimately impact cancer initiation, progression, and recurrence.3-7 Researchers
have further identified possible multi-directional associations among inflammation, immune processes, circadian
rhythms, and psychological stress wherein (1) synchronization of peripheral clock oscillations are thought to be
regulated through various interacting processes involving the sympathetic nervous system (SNS), hypothalamic-
pituitary adrenal (HPA) axis, and cyclical release of hormone (e.g., glucocorticoids), (2) hormone secretion,
immune cell processes (e.g., circulating concentration of cytokines, Leukocyte migration, T cell genesis), and
inflammatory responses are, in turn, regulated by diurnal patterns maintained by the central and peripheral
clocks, and (3) psychological stress can trigger a downstream reaction via the HPA axis and autonomic nervous
system (ANS) that, if chronic, can dysregulate immune system functioning, negatively impact tumor
microenvironment, and increase overall risk of morbidity in oncology populations.3-11 The availability and
accessibility of salivary biomarkers opens the door to a breadth of analyses otherwise inaccessible.15,16
Specifically, salivary samples can be collected multiple times per day across time allowing for the assessment
of diurnal variations in inflammatory processes that can help discern associations among circadian
dysregulations, alterations in immune functioning, psychological disturbances, and tumor growth and
proliferation in an effort to better serve the estimated 15 million people currently living with cancer in the United
States.1-2,13,17 Working hypotheses for the proposed study are: (1) salivary concentrations of pro-tumorigenic
cytokines of non-cancer controls will peak upon awakening and steadily decrease throughout the day, with the
exception of IL-6 for which there will be a secondary peak in the evening, (2) gynecologic oncology patients will
have significantly blunted diurnal rhythms for all salivary markers compared to non-cancer controls, and (3) main
effects of cancer stat...

## Key facts

- **NIH application ID:** 10017664
- **Project number:** 5F31CA247421-02
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Adaixa Padron
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $41,244
- **Award type:** 5
- **Project period:** 2019-12-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10017664

## Citation

> US National Institutes of Health, RePORTER application 10017664, Diurnal Variations in Salivary Concentrations of Pro-Tumorigenic Cytokines and Possible Effects of Psycho-Physiological Stress in Gynecologic Cancer Patients and Matched Healthy Controls (5F31CA247421-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10017664. Licensed CC0.

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