PROJECT SUMMARY
Obesity-related cancers, type 2 diabetes mellitus and cardiovascular disease, are characterized by a chronic
breakdown in metabolic functioning that impacts quality of life, physical functioning and longevity. Though
obesity plays a pivotal role in the etiology of at least 13 cancer types, the traditional metric for measuring
obesity, body mass index (BMI), is imperfect and may fail to identify a third of individuals at risk of these
cancers owing to metabolic dysfunction. While accumulated cellular damage and abrogated resilience
mechanisms are part of the natural aging process, damage accumulation and dysregulation of homeostasis
mechanisms, potentially driven by metabolic dysfunction, may lead to accelerated biological aging that has
recently been linked to cancer risk and survival. A better understanding of the relationship between metabolic
health, regardless of BMI, with accelerated aging and cancer is needed to inform who to target for prevention
efforts. The long-term goal of this application is to understand how metabolic dysfunction influences biological
aging and risk of cancer, at all levels of adiposity, to inform interventions that prevent or delay these deadly
diseases. The central hypothesis is that metabolic dysfunction, independent of obesity, is associated with
accelerated biological aging and obesity-related cancers. Aim 1 (F99 phase) will leverage data from the Utah
Obesity Study to measure the association between metabolic dysfunction (metabolic syndrome and diabetes)
across BMI categories (i.e., “metabolic health phenotype”) and risk of developing obesity-related cancer
(esophageal, gastric, colorectal, liver, gallbladder, pancreas, uterus, ovary, thyroid, meningioma, kidney, and
breast cancers, and multiple myeloma). In the Women’s Health Initiative (WHI), diabetes status at cancer
diagnosis will be measured in relation to cancer-specific and overall survival. This research will be extended in
Aim 2 (K00 phase) where metabolic health phenotype will be studied in relation to accelerated biological aging
and obesity-related cancer risk. In Aim 2a, data from the prospective WHI, Jackson Heart Study, Health and
Retirement Study, Framingham Heart Study and others will be used to measure the extent to which
accelerated biological age explains the association of metabolic health phenotype with obesity-related cancer
risk. In Aim 2b, using data from The Cancer Genomic Atlas (TCGA) cohort, accelerated biological aging will be
evaluated in relation to survival after obesity-related cancer diagnosis. The pre-doctoral to post-doctoral
candidate will expand upon her didactic and experiential training in biostatistics, epidemiology, aging and
epigenetics research both at the University of Utah, Huntsman Cancer Institute, and Yale School of Medicine.
Practical training will be obtained in human metabolism, biostatistics, epidemiology, aging and epigenetics
research. The proposed project will help to better identify those at risk of obesity-related cancers and support
changes in clinical cancer management to support diabetes and accelerated aging prevention.