Early Onset Cancers

In collaboration with Prof. Mary Beth Terry, Dr. Rebecca Kehm, and many others, we have conducted a series of studies examining recent trends in cancer incidence among younger adults in the United States and found substantial increases for select cancers. In particular, we found that three key cancers – colorectal, thyroid, and kidney – have increased significantly by birth year since 1945.  Some of these initial studies were supported by Columbia University’s Irving Institute for Cancer Dynamics and Data Science Institute. Supported by the National Cancer Institute (NCI), we are continuing this work to develop a comprehensive mathematical framework to identify causes behind the rising incidence in these three key early-onset cancers.

40 Years of Change in Age- and Stage-Specific Cancer Incidence Rates in US Women and Men
Studies have documented a temporal increase in incidence for several cancers in US young adults aged 25 to 39-years. To further characterize trends in young adults, we assessed age-specific and stage-specific incidence trends from 1975 to 2015, overall (all malignant cancers combined), and for 18 and 16 cancer sites in women and men, respectively, based on US population-based data from the Surveillance, Epidemiology, and End Results (SEER) Program.

We found that, overall cancer incidence increased by 1.15% (95% CI = 1.01% to 1.28%) per year in 25- to 39-year-old women and by 0.46% (95% CI = 0.17% to 0.75%) per year in 25- to 39-year-old men, during the time period after the most recent joinpoint inflection point. In comparison, annual percent changes (APCs) were of much lower magnitude in the older age groups (eg, 70- to 84-year-old women APC = −0.31%, 95% CI = −0.42% to −0.20%). We forecasted that overall cancer incidence will increase by an additional 11% by 2030 in 25- to 39-year-old women, and by an additional 12% in 25- to 39-year-old men. Ten of the 18 cancers assessed in 25- to 39-year-old women and 7 of the 16 cancers in 25- to 39-year-old men have been statistically significantly increasing over time. We found that the increase in incidence for young adults is stage specific for some cancers (eg, only nonlocalized breast cancer has increased in 25- to 39-year-old women).

Overall, we found that cancer incidence is increasing in young adults, particularly in young women.

For more details, see:
Kehm RD, Yang W, Tehranifar P, Terry MB. 40 Years of Change in Age- and Stage-Specific Cancer Incidence Rates in US Women and Men. JNCI Cancer Spectr. 2019;3(3):pkz038. doi: 10.1093/jncics/pkz038. 


Do Temporal Trends in Cancer Incidence Reveal Organ System Connections for Cancer Etiology?
To explore the drivers behind recent cancer incidence increases among young adults, we applied hierarchical cluster analysis to identify cancer anatomical clustering that may reveal systematic connections and common risk factors for those within the identified clusters. Our analysis included 48 anatomic sites and used cancer incidence data since 1973 for 25-39 year-olds.

Temporal trends mapped to three major clusters in men involving six organ systems (digestive, endocrine, urinary, blood, respiratory, and male genital) and one cluster in women involving five systems (digestive, endocrine, urinary, and female genital). For both men and women, kidney, thyroid, and colorectal cancers consistently clustered for all ages 25-39 and for each 5-year age subgroup. Further, several cancers linked to the endocrine and digestive systems (three in men and six in women) had highly consistent temporal incidence trends.

These findings suggest there may be organ system connections for cancers of the endocrine and digestive systems; etiologic approaches focused on clusters of cancers rather than individual cancers may prove fruitful.

For more details, please see:
Yang W, Terry MB. Do Temporal Trends in Cancer Incidence Reveal Organ System Connections for Cancer Etiology? Epidemiology. 2020;31(4):595-8. 

Model code for this study is available on Github: https://github.com/wan-yang/cancer_clusters


Survival model methods for analyses of cancer incidence trends in young adults
Recent studies have reported increases in cancer incidence in adults under 50 years. However, there remains uncertainty about whether these are true increases or a result of incidental findings from increased medical imaging. To evaluate these trends, we propose an alternative method to age-period-cohort analyses based on survival modeling. Simulations show that our method is capable of quantifying cohort effects within various backgrounds including increasing medical imaging. We applied the method to analyze the changes in cancer incidence rates for 44 anatomic sites, stratified by sex, by birth cohort for individuals born from 1945 to 1969 in the US based on incidence data from the Surveillance, Epidemiology, and End Results (SEER) program, and tested the validity of our models using later birth cohorts (1970-1974 and 1975-1979). We found that cancer risks have increased significantly in 15 sites (9 in men and 11 in women) for 25-49 year-olds. These results were consistent with previous findings from age-period-cohort analyses. Furthermore, based on our simulations, these increases were independent of increased medical imaging and support substantial, increased extrinsic risks in the identified cancers. Although our approach has several limitations including the restriction to the younger age range and requirement of complete data for all ages of interest, we demonstrate many advantages of our approach including the ease in implementation and interpretation of cohort effects, robustness to various period backgrounds, and ability to make predictions. Our approach should help epidemiologists evaluate cohort effects using incidence data for cancer or other diseases.

For detail about this method, please see:
Yang W, Kehm RD, Terry MB. Survival model methods for analyses of cancer incidence trends in young adults. Stat Med. 2020;39(7):1011-24.

Model code for this study is available on Github: https://github.com/wan-yang/cancer_cohort_trends