# UNCOVER: underlying novel causes of onset of very early cancer research

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $411,409

## Abstract

Recent studies, including our own, have shown dramatic increases in selected cancers among young adults.
Using U.S. SEER data, we showed that incidence rates of three key cancers have been increasing in younger
adults in the past decade: 318,781 adults aged 25–49 years were diagnosed with colorectal (n=114,220),
thyroid (n=146,977), and kidney (n=57,584) cancer with increases per year at 2.44%, 4.81%, and 3.83%,
respectively, during 2006–2015. Annual percent change over 1% per year is usually classified as an epidemic
of cancer. Thus, there is urgent public health need to understand the drivers of these early-onset cancers. We
have also modelled age-period-cohort effects and found that risks of developing these three cancers at younger
ages (25–49 years) have increased significantly by birth year for the last several decades. In addition, these
increases were consistently seen in most racial subgroups and in both localized and advanced cancers. These
findings suggest increased risks for these cancers due to increasing extrinsic (i.e., environmental and lifestyle)
risk factors, which, if identified, can be prevented. However, despite the dramatic increases in these early-onset
cancers, their relative rarity coupled with a long induction time make traditional epidemiologic approaches
inefficient to identify the underlying causes. For example, a population sample of more than 0.76 million would
be needed to observe 500 cases of colorectal cancer in adults under 50 over a 5-year period.
We thus propose to utilize a novel, and efficient, mathematical framework to investigate drivers of the three early-
onset cancers (i.e. colorectal, thyroid, and kidney). This framework will use mechanistic mathematical models to
capture the underlying cancer biology over the life course, and further couple these models with advanced data
assimilation methods to test various hypothesized risk mechanisms based on cancer incidence and exposures
recorded in nationally representative datasets. The project team has extensive experience using data
assimilation methods and mathematical models to understand disease systems including cancers. The
framework will also innovatively account for changing cancer detection rates over time, observation errors,
interactions among multiple risk factors, and changes in risk impact over the life course. Using this new
framework, for each of the three key cancers, we aim to 1) systematically examine and identify key risk factors,
in particular, in younger adults <50 years, 2) infer the risk mechanisms (e.g., cancer initiation vs. promotion), 3)
examine the dynamic interactions among co-exposures (e.g., risk amplification due to synergistic effect of co-
exposures), and 4) quantify the impact of individual risk factors and co-exposures in different stages of life and
particularly to examine critical windows of susceptibility. Further, we will quantify whether the identified etiological
factors when combined are of high enough magnitude to b...

## Key facts

- **NIH application ID:** 10303652
- **Project number:** 1R01CA257971-01A1
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Wan Yang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $411,409
- **Award type:** 1
- **Project period:** 2021-09-06 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10303652

## Citation

> US National Institutes of Health, RePORTER application 10303652, UNCOVER: underlying novel causes of onset of very early cancer research (1R01CA257971-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10303652. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*