Abstract
We estimated age-standardized cancer incidence (2010-2019) and mortality rates (2010-2022) in the U.S. to investigate whether cancer rates have increased at younger ages. Fourteen cancers had incidence rates that increased in at least one early onset age group (i.e., 15-29, 30-39, 40-49-year-olds) – 9 of these also increased in at least one older onset age group (i.e., 50-59, 60-69, 70-79) (i.e., female breast, colorectal, kidney, testicular, uterine and pancreatic cancers, and several lymphoid neoplasms). The largest absolute increases in 2019 compared to expected diagnoses based on 2010 rates were female breast (n=4,834 additional cancers), colorectal (n=2,099), kidney (n=1,793) and uterine cancers (n=1,209). While there were not concomitant increases in mortality rates for most cancers, colorectal, uterine and testicular cancer mortality rates increased in early onset age groups. The drivers of rising incidence rates are cancer-specific and could include a combination of established and perhaps new etiologic factors, and increased detection.
Significance
In the U.S., incidence rates of some cancers have increased in early onset age groups. For many of these cancers, rates have also increased in older age groups, suggesting that the impact of changes in risk factor prevalence and/or improvements in detection could impact risk across the age range.
Introduction
In recent years, there has been growing concern about rising cancer incidence rates at younger ages (1). Studies have shown that rates of early onset cancers, often defined as cancers occurring before age 50, have increased for certain cancer types in the U.S. as well as across many other countries (2-4), with emphasis on rising rates of early onset gastrointestinal, particularly colorectal and pancreatic, female breast and uterine cancers. Recent work in the U.S. also has shown that younger birth cohorts have a higher risk of select cancer types compared to older birth cohorts (3,5,6).
These data have prompted speculation that we are facing a national or even global epidemic of early onset cancers (2). Proposed explanations for these increases vary by cancer site, and include increased screening and incidental detection, an increased prevalence of obesity and diabetes, Westernized diet and ultra-processed foods, prenatal exposures and changes in reproductive factors, the microbiome and other environmental exposures (2,3,6,7).
In order to understand the landscape of early onset cancer risk in the U.S., comprehensive descriptive analyses of cancer incidence and mortality trends throughout the age range are needed. Here, we use national data to conduct a detailed analysis of cancer incidence, including analyses of cancer subtypes and stage at diagnosis, and mortality trends for 33 cancer types among 15-29, 30-39 and 40-49-year-olds compared to older age groups through ages 70-79 years. These comparisons will enable identification of cancers with incidence rates increasing only in early onset age groups and those increasing across the age range. In this regard, our findings could generate insights into risk factors, both new and established, that are particularly important in early age groups.
Results
Description of Cancer Cases
In the U.S., during 2010-2019, 2,020,829 early-onset incident cancers were diagnosed among 15–29-year-olds (1.9% of all cancers in 15-79-year-olds; age-standardized incidence rate=39.8 per 100,000), 30–39-year-olds (3.6%; 123.5) and 40-49-year-olds (8.4%; 293.9)(Supplemental Table 1). 63.2% of early-onset cancers occurred among females. The most common early onset cancer types were breast, thyroid, and melanoma among females and colorectal, testicular, and melanoma among males.
Trends in Total Cancer Incidence and Mortality
Among 15-29-year-olds, age-standardized cancer rates increased 1.05% (95%CI 0.57, 2.34) per year during 2010-2015, and then declined 0.73% (95%CI −2.27, −0.06) per year during 2015-2019 (Figure 1; Table 1). Among 30-39-year-olds, cancer rates increased 1.25% (95%CI 0.88, 2.48) per year during 2010-2016 and then were flat during 2016-2019, and among 40-49-year-olds there was no significant change in cancer rates over the full time period. Analyses by sex showed that cancer incidence rates were stable in the most recent time period across each early onset age group among males, while, among females, rates declined significantly 0.90% (95%CI −1.90, −0.30) per year among 15-29-year-olds during 2015-2019, were stable among 30-39-year-olds, and increased 0.56% (95%CI 0.35, 0.75) per year during 2010-2019 among 40-49-year-olds.
Figure 1.
Age-standardized total cancer incidence (2010-2019) and mortality (2010-2022) rates by age group and sex in the United States. Points represent observed data and lines represent modeled trends. Red indicates statistically significant increasing trends in the most recent time period, blue indicates statistically significant decreasing trends in the most recent time period, and black lines indicate stable rates in the most recent time period.
Table 1.
Age-standardized total cancer incidence (2010-2019) and mortality (2010-2022) estimates and trends in the United States by age group and sex.
| Incidence | Mortality | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Sex |
Age
Group |
2010
Rate |
2019
Rate |
Trend | Years | APC, 95% CI |
2010
Rate |
2022
Rate |
Trend | Years | APC, 95% CI |
| Males and Females | 15-29 | 38.8 | 39.5 | Trend 1 | 2010-2015 | 1.05 (0.57, 2.34) | 4.61 | 4.00 | Trend 1 | 2010-2020 | −1.88 (−3.36, −1.45) |
| Trend 2 | 2015-2019 | −0.73 (−2.27, −0.06) | Trend 2 | 2020-2022 | 2.32 (−1.36, 4.50) | ||||||
| 30-39 | 118.6 | 125.6 | Trend 1 | 2010-2016 | 1.25 (0.88, 2.48) | 15.7 | 14.8 | Trend 1 | 2010-2022 | −0.59 (−0.86, −0.33) | |
| Trend 2 | 2016-2019 | −0.62 (−2.78, 0.38) | |||||||||
| 40-49 | 292.8 | 296.6 | Trend 1 | 2010-2019 | 0.07 (−0.12, 0.26) | 56.3 | 44.8 | Trend 1 | 2010-2018 | −2.47 (−2.88, −2.25) | |
| Trend 2 | 2018-2022 | −0.62 (−1.34, 0.92) | |||||||||
| Males | 15-29 | 35.4 | 36.0 | Trend 1 | 2010-2019 | 0.28 (−0.39, 0.94) | 5.30 | 4.51 | Trend 1 | 2010-2020 | −2.06 (−6.15, 3.52) |
| Trend 2 | 2020-2022 | 3.59 (−2.85, 7.34) | |||||||||
| 30-39 | 82.9 | 85.3 | Trend 1 | 2010-2016 | 0.92 (0.58, 2.44) | 14.0 | 13.0 | Trend 1 | 2010-2020 | −1.21 (−2.66, −0.80) | |
| Trend 2 | 2016-2019 | −0.55 (−2.52, 0.31) | Trend 2 | 2020-2022 | 1.96 (−0.87, 3.70) | ||||||
| 40-49 | 219.9 | 206.5 | Trend 1 | 2010-2014 | −1.29 (−2.29, −0.78) | 52.3 | 40.0 | Trend 1 | 2010-2017 | −3.14 (−5.26, −2.54) | |
| Trend 2 | 2014-2019 | −0.41 (−0.82, 0.68) | Trend 2 | 2017-2022 | −0.86 (−1.99, 2.07) | ||||||
| Females | 15-29 | 42.3 | 43.1 | Trend 1 | 2010-2015 | 1.24 (0.79, 2.01) | 3.89 | 3.46 | Trend 1 | 2010-2022 | −1.44 (−2.20, −0.70) |
| Trend 2 | 2015-2019 | −0.90 (−1.90, −0.30) | |||||||||
| 30-39 | 154.2 | 166.4 | Trend 1 | 2010-2015 | 1.69 (1.10, 3.99) | 17.3 | 16.6 | Trend 1 | 2010-2022 | −0.31 (−0.67, 0.06) | |
| Trend 2 | 2015-2019 | −0.20 (−2.80, 0.58) | |||||||||
| 40-49 | 364.5 | 385.2 | Trend 1 | 2010-2019 | 0.56 (0.35, 0.75) | 60.2 | 49.7 | Trend 1 | 2010-2019 | −1.97 (−3.25, −1.61) | |
| Trend 2 | 2019-2022 | −0.36 (−1.75, 1.37) | |||||||||
APC: Annual percentage change in incidence or mortality rates.
Rates are age-standardized and presented per 100,000 person-years. Bold indicates statistically significant trends. 95% confidence intervals (CIs) s were calculated in Joinpoint using the Empirical Quantile Method.
Cancer mortality rates did not increase significantly across any age group. Cancer mortality rates declined 1.88% (95%CI −3.36, −1.45) per year during 2010-2020, and then were stable during 2020-2022 among 15-29-year-olds, declined 0.59% (95%CI −0.86, −0.33) per year during 2010-2022 among 30-39-year-olds, and declined 2.47% (95%CI −2.88, −2.25) per year during 2010-2018 and then were stable during 2018-2022 among 40-49-year-olds (Table 1).
Overall trends in early onset cancer incidence rates are driven by heterogenous trends across cancer types. Out of 33 cancer types occurring among 15-49-year-olds considered in this analysis, fourteen cancer types had significantly increasing incidence rates in the most recent time period in at least one early onset age group, and 18 cancer types had significantly decreasing incidence rates in the most recent time period in at least one early onset age group. Here we focus on cancers with increasing cancer rates, though APCs for all cancer types examined can be found in Supplemental Table 2.
Cancers with Incidence Rates Increasing Only in Early Onset Age Groups
Age-standardized incidence rates of melanoma, cervical cancer, stomach cancer, plasma cell neoplasms, and cancer of the bones and joints each increased significantly in one early onset age group in the most recent time period (Figures 2A-E, Table 2), but there were no corresponding increases in older onset cancer rates (i.e., 50-59, 60-69, 70–79-year-olds). For example, during 2010-2019 among 30-39-year-olds, cervical cancer rates increased 1.39% (95%CI 0.65, 2.15) per year. Among 40-49-year-olds during 2010-2019, there was a 0.82% (95%CI 0.10, 1.51) annual increase in melanoma rates, 1.38% (95%CI 0.85, 1.92) increase in stomach cancer rates and 1.58% (95%CI 0.94, 2.19) increase in plasma cell neoplasm rates. Rates of cancer of the bones and joints increased 2.37% (95%CI 0.62, 7.03) per year in 40-49-year-olds during 2013-2019.
Figure 2.
Age-standardized cancer incidence (2010-2019) and mortality (2010-2022) rates by age group and cancer type in the United States for a) melanoma, b) cervix cancer, c) stomach cancer, d) bones and joints cancer and e) plasma cell neoplasms. In the first and second panel of each set of figures, points represent observed data and lines represent modeled trends. The third panel represents annual percent changes (APCs) in age-standardized incidence rates in the most recent time period, stratified by stage at diagnosis. Points represent APCs and lines represent 95% confidence intervals. In all panels, red indicates statistically significant increasing trends in the most recent time period, blue indicates statistically significant decreasing trends in the most recent time period, and black lines indicate stable rates in the most recent time period.
Table 2.
Age-standardized trends in cancer incidence (2010-2019) and mortality (2010-2022) among 15-29, 30-39 and 40-49-year-olds by cancer type.
| Incidence | Mortality | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
|
Cancer
Type |
Age
Group |
2010
Rate |
2019
Rate |
Trend | Years | APC, 95% CI |
2010
Rate |
2022
Rate |
Trend | Years | APC, 95% CI |
| Stomach Cancer | 15-29 | 0.22 | 0.24 | Trend 1 | 2010-2019 | 1.57 (−0.33, 3.55) | 0.10 | 0.08 | Trend 1 | 2010-2022 | −1.02 (−3.54, 1.58) |
| 30-39 | 1.50 | 1.49 | Trend 1 | 2010-2019 | 1.33 (−0.25, 3.00) | 0.62 | 0.58 | Trend 1 | 2010-2022 | −0.60 (−1.31, 0.12) | |
| 40-49 | 3.86 | 4.17 | Trend 1 | 2010-2019 | 1.38 (0.85, 1.92) | 1.72 | 1.62 | Trend 1 | 2010-2022 | −0.15 (−1.23, 0.95) | |
| Colorectal Cancer | 15-29 | 1.04 | 1.00 | Trend 1 | 2010-2019 | −0.26 (−1.46, 0.92) | 0.24 | 0.18 | Trend 1 | 2010-2022 | −1.52 (−3.21, 0.18) |
| 30-39 | 6.97 | 8.07 | Trend 1 | 2010-2019 | 1.69 (0.91, 2.50) | 1.60 | 1.97 | Trend 1 | 2010-2022 | 1.17 (0.54, 1.83) | |
| 40-49 | 23.1 | 26.7 | Trend 1 | 2010-2019 | 1.71 (1.19, 2.24) | 5.98 | 6.55 | Trend 1 | 2010-2022 | 1.08 (0.64, 1.53) | |
| Pancreatic Cancer | 15-29 | 0.15 | 0.29 | Trend 1 | 2010-2019 | 7.05 (4.03, 10.58) | 0.04 | 0.03 | Trend 1 | 2010-2022 | −2.51 (−6.66, 1.51) |
| 30-39 | 0.88 | 1.12 | Trend 1 | 2010-2015 | 7.59 (5.43, 11.91) | 0.42 | 0.40 | Trend 1 | 2010-2012 | −5.76 (−11.42, 2.25) | |
| Trend 2 | 2015-2019 | −1.20 (−5.69, 1.45) | Trend 2 | 2012-2016 | 6.43 (1.32, 11.59) | ||||||
| Trend 3 | 2016-2022 | −2.92 (−6.16, −1.11) | |||||||||
| 40-49 | 4.25 | 4.89 | Trend 1 | 2010-2019 | 1.25 (0.86, 1.66) | 2.86 | 2.65 | Trend 1 | 2010-2018 | −0.94 (−3.57, −0.12) | |
| Trend 2 | 2018-2022 | 1.18 (−0.51, 4.45) | |||||||||
| Bones and Joint Cancer | 15-29 | 0.96 | 0.97 | Trend 1 | 2010-2017 | 1.36 (−0.20, 6.65) | 0.42 | 0.46 | Trend 1 | 2010-2018 | −1.36 (−3.14, −0.35) |
| Trend 2 | 2017-2019 | −3.99 (−9.18, 1.10) | Trend 2 | 2018-2022 | 4.65 (1.94, 9.85) | ||||||
| 30-39 | 0.61 | 0.73 | Trend 1 | 2010-2019 | 1.65 (−0.49, 3.94) | 0.21 | 0.22 | Trend 1 | 2010-2022 | 1.10 (−0.37, 2.75) | |
| 40-49 | 0.74 | 0.84 | Trend 1 | 2010-2013 | −2.18 (−6.88, 1.32) | 0.26 | 0.25 | Trend 1 | 2010-2022 | 0.63 (−0.95, 2.28) | |
| Trend 2 | 2013-2019 | 2.37 (0.62, 7.03) | |||||||||
| Melanoma | 15-29 | 3.58 | 2.53 | Trend 1 | 2010-2016 | −2.78 (−3.45, −1.55) | 0.18 | 0.07 | Trend 1 | 2010-2022 | −7.56 (−11.26, −4.41) |
| Trend 2 | 2016-2019 | −6.85 (−10.7, −5.01) | |||||||||
| 30-39 | 11.3 | 11.3 | Trend 1 | 2010-2019 | 0.45 (−0.48, 1.42) | 0.66 | 0.45 | Trend 1 | 2010-2022 | −4.51 (−6.49, −2.67) | |
| 40-49 | 18.4 | 19.6 | Trend 1 | 2010-2019 | 0.82 (0.10, 1.51) | 1.64 | 0.94 | Trend 1 | 2010-2022 | −4.90 (−5.92, −3.99) | |
| Female Breast Cancer | 15-29 | 3.50 | 4.09 | Trend 1 | 2010-2019 | 1.85 (0.96, 2.77) | 0.21 | 0.26 | Trend 1 | 2010-2019 | 2.63 (1.36, 13.06) |
| Trend 2 | 2019-2022 | −4.81 (−15.46, 0.66) | |||||||||
| 30-39 | 44.7 | 49.4 | Trend 1 | 2010-2019 | 0.91 (0.40, 1.43) | 4.56 | 4.52 | Trend 1 | 2010-2022 | −0.12 (−1.13, 0.89) | |
| 40-49 | 150.2 | 166.0 | Trend 1 | 2010-2019 | 0.91 (0.53, 1.28) | 16.5 | 13.4 | Trend 1 | 2010-2022 | −1.74 (−2.12, −1.39) | |
| Cervical Cancer | 15-29 | 2.07 | 1.50 | Trend 1 | 2010-2016 | −0.47 (−1.59, 0.85) | 0.25 | 0.09 | Trend 1 | 2010-2017 | −1.22 (−4.28, 4.70) |
| Trend 2 | 2016-2019 | −9.25 (−13.75, −6.55) | Trend 2 | 2017-2022 | −13.9 (−25.3, −8.90) | ||||||
| 30-39 | 12.2 | 13.2 | Trend 1 | 2010-2019 | 1.39 (0.65, 2.15) | 1.76 | 1.65 | Trend 1 | 2010-2022 | 0.54 (−0.64, 1.81) | |
| 40-49 | 14.5 | 15.2 | Trend 1 | 2010-2019 | 0.63 (−0.003, 1.24) | 3.38 | 3.47 | Trend 1 | 2010-2022 | 0.12 (−0.73, 0.94) | |
| Uterine Cancer | 15-29 | 0.75 | 0.96 | Trend 1 | 2010-2019 | 2.19 (0.69, 3.78) | |||||
| 30-39 | 6.78 | 8.67 | Trend 1 | 2010-2019 | 2.63 (1.56, 3.76) | 0.41 | 0.56 | Trend 1 | 2010-2022 | 2.68 (0.31, 5.41) | |
| 40-49 | 19.8 | 23.0 | Trend 1 | 2010-2019 | 1.83 (0.66, 3.01) | 1.45 | 1.78 | Trend 1 | 2010-2022 | 2.11 (0.12, 4.21) | |
| Testicular Cancer | 15-29 | 9.13 | 8.80 | Trend 1 | 2010-2017 | 0.67 (0.23, 2.27) | 0.31 | 0.29 | Trend 1 | 2010-2022 | 0.93 (−1.17, 3.22) |
| Trend 2 | 2017-2019 | −2.88 (−5.36, −0.36) | |||||||||
| 30-39 | 12.4 | 13.4 | Trend 1 | 2010-2019 | 1.15 (0.07, 2.29) | 0.45 | 0.60 | Trend 1 | 2010-2020 | 1.53 (−7.86, 13.06) | |
| Trend 2 | 2020-2022 | 14.2 (1.72, 24.2) | |||||||||
| 40-49 | 7.46 | 7.91 | Trend 1 | 2010-2015 | −0.28 (−2.17, 0.43) | 0.39 | 0.35 | Trend 1 | 2010-2022 | 0.12 (−3.30, 3.66) | |
| Trend 2 | 2015-2019 | 1.59 (0.59, 3.79) | |||||||||
| Kidney Cancer | 15-29 | 0.62 | 0.78 | Trend 1 | 2010-2019 | 1.63 (−0.11, 3.43) | 0.07 | 0.07 | Trend 1 | 2010-2022 | −0.84 (−3.22, 1.67) |
| 30-39 | 4.58 | 5.26 | Trend 1 | 2010-2019 | 1.89 (0.63, 3.21) | 0.25 | 0.23 | Trend 1 | 2010-2022 | −1.31 (−3.58, 1.00) | |
| 40-49 | 12.4 | 15.7 | Trend 1 | 2010-2019 | 2.63 (2.02, 3.24) | 1.35 | 1.08 | Trend 1 | 2010-2022 | −1.92 (−2.56, −1.29) | |
| Precursor B NHL | 15-29 | 0.90 | 0.99 | Trend 1 | 2010-2019 | 1.40 (−0.25, 3.11) | |||||
| 30-39 | 0.54 | 0.64 | Trend 1 | 2010-2019 | 1.56 (0.13, 3.09) | ||||||
| 40-49 | 0.58 | 0.82 | Trend 1 | 2010-2019 | 3.21 (1.19, 5.34) | ||||||
| DLBCL | 15-29 | 1.04 | 1.15 | Trend 1 | 2010-2019 | 0.98 (0.31, 1.66) | |||||
| 30-39 | 2.32 | 2.45 | Trend 1 | 2010-2019 | 0.71 (−0.57, 2.03) | ||||||
| 40-49 | 4.42 | 4.12 | Trend 1 | 2010-2019 | −0.59 (−1.09, −0.11) | ||||||
| MF/SS | 15-29 | 0.12 | 0.16 | Trend 1 | 2010-2019 | 2.61 (0.23, 5.03) | |||||
| 30-39 | 0.29 | 0.39 | Trend 1 | 2010-2012 | 13.18 (−3.37, 43.28) | ||||||
| Trend 2 | 2012-2019 | 0.71 (−18.85, 12.13) | |||||||||
| 40-49 | 0.45 | 0.54 | Trend 1 | 2010-2019 | 3.00 (0.71, 5.36) | ||||||
| Plasma cell neoplasms | 15-29 | 0.06 | 0.04 | Trend 1 | 2010-2019 | −2.91 (−9.54, 3.74) | |||||
| 30-39 | 0.67 | 0.74 | Trend 1 | 2010-2019 | 0.70 (−0.61, 2.03) | 0.08 | 0.07 | Trend 1 | 2010-2022 | −3.14 (−6.63, 0.28) | |
| 40-49 | 3.00 | 3.47 | Trend 1 | 2010-2019 | 1.58 (0.94, 2.19) | 0.56 | 0.42 | Trend 1 | 2010-2015 | 1.26 (−2.41, 14.58) | |
| Trend 2 | 2015-2022 | −4.23 (−17.38, −1.49) | |||||||||
APC: Annual percentage change. Rates are age-standardized and presented per 100,000 person-years. Table only includes cancer types where rates increased significantly in the most recent segment in at least one age group. Mortality rates for specific lymphoid neoplasms were not available. Plasma cell neoplasm death rates are restricted to multiple myelomas.
Sex-stratified results are presented in Supplemental Figure 1A-J. Melanoma rates increased across multiple age categories among females only with no increases observed among males (Supplemental Figure 1A). Trends in stomach cancer rates also differed by sex with increases observed only for 15-29-year-old males and 40-49-year-old females (Supplemental Figure 1B). Increases in plasma cell neoplasm rates were only observed among females. In contrast to incidence, cancer mortality rates did not significantly increase in any early onset age group for these cancer types, except for cancer of the bones and joints among 15-29-year-olds (Figure 2D).
Cancers with Incidence Rates Increasing in both Early Onset and Older Age Groups
Age-standardized rates of female breast, colorectal, kidney, testicular, uterine corpus (i.e., uterine) and pancreatic cancers, and precursor B cell non-Hodgkin lymphoma (NHL), diffuse large B cell lymphoma (DLBCL), and mycosis fungoides/Sezary syndrome (MF/SS) increased significantly in at least one early onset age group in the most recent time period, and also increased significantly in at least one older onset age group (i.e., 50-59, 60-69 or 70-79-year-olds) (Figures 3A-F and 4A-C, Table 1). For example, during 2010-2019, female breast cancer rates increased in every age group, except for 60-69-year-olds, with annual increases of 1.85% (95%CI 0.96, 2.77) among 15-29-year-olds, 0.91% (95%CI 0.40, 1.43) for 30-39-year-olds, 0.91% (95%CI 0.53, 1.28) for 40-49-year-olds, 0.89% (95%CI 0.66, 1.13) for 50-59-year-olds and 0.86% (95%CI 0.63, 1.11) for 70-79-year-olds (Figure 3A). Colorectal cancer incidence rates increased 1.69% (95%CI 0.91, 2.50) per year among 30-39-year-olds, 1.71% (95%CI 1.19, 2.24) per year among 40-49-year-olds and 0.88% (95%CI 0.32, 1.46) per year among 50-59-year-olds, but declined significantly by 1.61% (95%CI −1.84, −1.38) per year among 60-69-year-olds and 3.64% (95%CI −3.84, −3.44) per year among 70-79-year-olds (Figure 3B). Kidney cancer rates increased across every age group except 15-29-year-olds, with the most rapid increase among 40-49-year-olds (2.63%; 95%CI 2.02, 3.24) per year; Figure 3C). Uterine cancer rates increased annually 2.19% (95%CI 0.69, 3.78) in 15-29-year-olds, 2.63% (95%CI 1.56, 3.76) among 30-39-year-olds, 1.83% (95%CI 0.66, 3.01) among 40-49-year-olds and 1.71% (95%CI 1.25, 2.20) among 70-79-year-olds (Figure 3E). Rates among 50-59 and 60-69-year-old women increased through 2016 and then flattened. Stage-specific increases in rates differed by cancer type and age group and were not restricted to any one stage within a cancer type. Among these cancer types, early onset cancer mortality rates increased among 30-39-year-olds for testicular cancer, 30-39 and 40-49-year-old women for uterine cancer, and 30-39 and 40-49-year-olds for colorectal cancer – mortality rates for each of these cancer types also increases in at least one older age group (Figures 3B and D).
Figure 3.
Age-standardized cancer incidence (2010-2019) and mortality (2010-2022) rates by age group and cancer type in the United States for a) female breast cancer, b) colon and rectum cancer, c) kidney cancer, d) testis cancer, e) uterine corpus cancer and f) pancreatic cancer In the first and second panel of each set of figures, points represent observed data and lines represent modeled trends. The third panel represents annual percent changes (APCs) in age-standardized incidence rates in the most recent time period, stratified by stage at diagnosis. Points represent APCs and lines represent 95% confidence intervals. In all panels, red indicates statistically significant increasing trends in the most recent time period, blue indicates statistically significant decreasing trends in the most recent time period, and black lines indicate stable rates in the most recent time period.
Figure 4.
Age-standardized cancer incidence (2010-2019) by age group and cancer type in the United States for a) precursor B cell non-Hodgkin lymphoma, b) diffuse large B cell lymphoma, and c) mycosis fungoides and Sézary syndrome. Points represent observed data and lines represent modeled trends. In all panels, red indicates statistically significant increasing trends in the most recent time period, blue indicates statistically significant decreasing trends in the most recent time period, and black lines indicate stable rates in the most recent time period.
Trends in Cancer Incidence Rates by Subtype
We observed some differences in the incidence trends in analyses stratifying female breast cancer incidence by ER status (ER-positive, ER-negative), colorectal cancer by topography (colon, rectum), uterine cancer by histology (i.e., endometrioid, non-endometrioid, sarcoma/other), kidney cancer by histology (i.e., renal cell carcinoma, transitional cell carcinoma), and stomach cancer by topography (cardia, non-cardia) (Supplemental Figures 2-6). ER-negative breast cancer rates increased significantly among 20-29-year-old females during 2010-2019, but were stable among 30-39-year-olds, and decreased among 40-49-year-old females. In contrast, rates of ER-positive breast cancers were stable during 2013-2019 among 20-29-year-old females but increased significantly among 30-39 and 40-49-year-old females. When colorectal cancer was stratified by topography, colon cancer rates increased significantly among 40-49-year-olds, while rectal cancer rates increased significantly among 30-39-year-olds and 40-49-year-olds. Endometrioid uterine cancer rates increased significantly among 15-29, 30-39 and 40-49-year-olds, while rates of non-endometrioid and sarcoma/other histologies did not increase in early onset age groups. For kidney cancer, rates of renal cell carcinoma (the most common subtype) increased significantly among 30-39 and 40-49-year-olds, while there were no significant increases in early onset transitional cell carcinoma. Rates of both cardia and non-cardia stomach cancer increased among 30-39-year-olds.
Cancer Rates Decreasing in Early Onset Age Groups
Of the 18 cancer types with decreasing incidence rates in at least one early onset age group, the most rapid declines in the most recent time period were observed among 40-49-year-olds for Kaposi sarcoma (−9.22% [95%CI −12.29, −7.86] per year, 2014-2019), liver cancer (−5.25% [95%CI −6.68, −3.99] per year, 2010-2019) and Burkitt lymphoma (−4.91% [95%CI −8.42, −1.68] per year, 2010-2019). The largest absolute declines were observed for prostate, lung and ovarian cancers.
Estimated Number of Additional Early Onset Cancers Diagnosed in 2019
We estimated the number of additional early onset cancers that occurred in 2019 compared to 2010 (Figure 5A and B). Among 15-49-year-olds, rising incidence rates resulted in increases in the absolute numbers of cancers diagnosed in 2019 relative to 2010 for each of the 14 cancer types highlighted above, except melanoma. The largest increases in 2019 were observed for female breast (n=4,834 additional cancers), colorectal (n=2,099), kidney (n=1,793), uterine (n=1,209), and pancreas cancers (n=511). Each remaining cancer type contributed fewer than 350 additional early onset cancer cases. When restricted to females aged 20-49 years, there were 5,183 additional ER-positive cancers and 411 fewer ER-negative cancers in 2019.
Figure 5.
A) Observed (black bar) and expected (gray bar) number of cancer diagnoses in 2019 among 15-49-year-olds. B) Observed minus expected number of cancer diagnoses (i.e., additional cancer diagnoses) in 2019 among 15-49-year-olds. Expected number of cases were estimated by multiplying 2010 age-specific cancer incidence rates by population counts for 2019.
Discussion
As of 2019, recent trends in age-standardized total cancer incidence rates in the U.S. did not increase significantly among 15-29, 30-39 or 40-49-year-olds. Total cancer incidence rates did increase significantly among 40-49-year-old women, but not men. In addition, there have been significant increases in early onset cancer incidence rates for certain cancer types. Some of these increases have occurred exclusively in early onset age groups (melanoma, cervical cancer, stomach cancer, plasma cell neoplasms and cancer of the bones and joints), while others have occurred alongside increases in incidence in older age groups (female breast, colorectal, kidney, testicular, uterine, pancreatic cancer and several types of lymphomas). Female breast, colorectal, kidney and uterine cancers contributed the largest number of additional early onset cancers in 2019 (>80% of the total number of estimated additional cancers). There were also strong decreases in cancer rates in early onset age groups for certain cancer types, most notably lung and prostate cancers. Cancer mortality rates increased in some early onset age groups for a limited number of cancer types, notably colorectal and uterine cancers, but not for most other cancer types with increasing incidence.
A constellation of factors should be considered when interpreting increasing incidence rates of certain cancer types over time, including etiologic factors that may result in a true increase in disease occurrence, changes in cancer screening or detection that may result in cancer diagnoses at earlier ages, as well as updates to clinical diagnosis or coding of cancers that might result in spurious increases based on classification changes. It is possible that increased screening for and detection of Lynch syndrome (higher risk of colorectal and uterine cancers), BRCA1 and BRCA2 (higher risk of breast and ovarian cancers) and other genetic variants (8,9) could have increased cancer surveillance in high-risk individuals, which could result in earlier cancer diagnoses and increasing rates over time in younger age groups. While these genetic predispositions are rare, and the majority of early onset cancers are sporadic, even a relatively limited number of additional diagnoses could have contributed, given the relatively small absolute increase in the number of cases of certain cancers. Many of the cancer types that increased over time in early onset age groups also increased in at least one older age group, suggesting that the impact of changes in the prevalence of risk factors and/or improvements in detection could impact risk across the age range.
A national increase in obesity has been hypothesized to be a contributor to increasing early onset cancer rates in the U.S. and worldwide, as well as increases at older ages. Obesity rates among young and mid-life adults have increased substantially over time in the U.S. Among 35-44-year-olds, the prevalence of obesity increased from 21.3% in 1988-94 to 42.5% in 2015-18 among men and from 25.5% to 45.0% among women (10). Obesity is a risk factor for seven of the cancer types with increasing rates in early onset age groups – colorectal, kidney, uterine, pancreatic, stomach (cardia), cervical cancers and myeloma (i.e., plasma cell neoplasms), with population attributable fractions in 2019 ranging from 5.3% of colorectal cancers to 53.1% of uterine cancers (11). Though the majority of estimates quantifying the association between excess body weight and cancer risk come from cohorts of older men and women, there is some evidence that obesity at younger ages contributes to cancer risk, including cancers diagnosed in early onset age groups (12-14). Obesity may also contribute to increased cervical cancer risk through decreased detection of precancers during screening (15). Other related factors such as lack of physical activity, rising prevalence of diabetes, and Western diets have also been implicated in rising rates of early onset cancer (2,3,6).
Whether environmental factors known or suspected to be carcinogenic (e.g., outdoor air pollution, per- and polyfluoroalkyl substances) contribute to some of these increases is unclear. However, in order for a particular environmental risk factor to explain trends across multiple cancer sites, such exposures would have to be nearly ubiquitous, lead to carcinogenesis at multiple organ sites and have increased in prevalence or intensity in recent decades. Although possible, no factors meeting these criteria have been identified. Other environmental or lifestyle factors with known or suspected associations with cancer risk with differential prevalence of use by age group, such personal care or hygiene products use, may be associated with rising rates of specific cancers, such as uterine and breast cancers (16,17).
Rising rates of early onset female breast cancer contributed to the largest absolute increase in incident cases in 2019 relative to 2010. Though obesity is known to increase risk of post-menopausal breast cancer, it is associated inversely with pre-menopausal breast cancer (18). Earlier age at menarche, lower parity and older age at first birth in successive birth cohorts of women are hormone-related risk factors that may contribute to increasing rates of early onset ER-positive breast cancers (19). In contrast to increasing ER-positive breast cancer, ER-negative breast cancer incidence has been largely stable or decreasing among women aged ≥30 years; however, we observed an increasing rate of early onset ER-negative breast cancer among 20–29-year-old women.
Increases in female breast cancer incidence, particularly localized cancer, may be due to advances in screening technologies (i.e., improved detection) as well as changes in breast cancer screening guidelines over time. For example, digital breast tomosynthesis was introduced in 2011, and there has been an increase over time in supplemental screening, particularly for women with dense breasts (20,21). It is challenging to directly relate changes in breast cancer screening guidelines with breast cancer incidence rates, as screening recommendations have changed several times in recent decades and differ across agencies. During 2009-2024, the United States Preventive Services Task Force (USPSTF) (22) recommended discussion between patients and their primary care clinicians about screening before age 50, while the American Cancer Society has recommended annual screening for women aged 45-54 and optional screening for women aged 40-44 since 2015 (23). In 2022, 59% of 40-49-year-old women had reported mammography during the previous 2 years (24). Breast cancer rates increased exclusively for localized disease in this age group, consistent with a potential impact of increased screening uptake on breast cancer incidence. However, younger women at average breast cancer risk are not recommended to receive breast cancer screening, and localized, regional and distant stage tumors have increased over time among 30-39-year-olds, arguing against changes in screening recommendations and improvements in screening technology as a sole explanation. Of note, in 2024 the USPSTF updated breast cancer screening guidelines to include women starting at age 40, though these changes would not have impacted our results (25).
Increasing rates of colorectal cancer have been reported extensively, both in the U.S. and globally (2,4,26). We observed increasing colorectal cancer rates among 30-39, 40-49 and 50-49-year-olds, and decreasing rates in 60-69- and 70–79-year-olds. Studies that have examined modifiable risk factors and early onset colorectal cancer risk are based on a limited number of cases and incomplete exposure information in the relevant time period (12,27,28). In addition to obesity, physical inactivity and sedentary time, dietary patterns, alcohol drinking, and antibiotics have been implicated in rising rates (29,30). Of note, appendix cancers are sometimes included in the definition of colorectal cancer despite molecular differences (31), but were excluded from this analysis due to classification changes that resulted in very rapid, artifactual increases in appendix cancer rates over time (4,32). It is unclear if changing screening rates at younger ages have impacted early onset colorectal cancer incidence. In both 2008 and 2016, the USPSTF recommended screening for colorectal cancer for 50-75-year-olds (33). Though screening among those <50-years-old was not recommended during the study time period, 21% of 45-49-year-olds were up to date on their colorectal cancer screening in 2019 (34). Depending on the modality, increased screening at younger ages could either decrease cancer rates through removal of precancerous polyps or increase cancer rates with earlier detection. Earlier detection would most likely result in increases in localized stage disease, but only increases in regional stage disease were observed. It is difficult to know whether rising rates are truly limited to those younger than 60, or if the same etiologic factors would have also caused increasing rates of older onset colorectal cancers in the absence of screening. For example, a recent international analysis highlighted that rising rates of colorectal cancer are not exclusive to early onset cancers in many countries in the world (35). USPSTF expanded recommendations for colorectal cancer screening to include 45-49-year-olds in 2021, though this change would not have impacted the estimates presented here (36). Studies have noted that early onset cases of colorectal and breast cancer, as well as other cancer types, are more likely to be advanced stage at diagnosis. However, this could be due to the lack of screening at younger ages (2).
Kidney cancer rates increased across nearly every age group without a complementary increase in mortality rates. These increases were exclusively observed for renal cell carcinoma, and have been partially attributed to incidental detection of tumors during imaging with CT scans and MRIs (37), though the increases observed in the current study were not restricted to localized stage disease. Rising obesity prevalence has contributed to rising rates of renal cell carcinoma in the U.S. among older people, but the impact has not been quantified in early onset renal cell carcinoma cases (38). A prior study showed increasing rates of kidney cancer among 30-39-year-olds across Hispanic, Black and White men and women, with the most rapid increases occurring among Hispanic individuals and the highest rates among Black men (39).
We observed strong increases in uterine cancer rates across all early onset age groups, with an increase in mortality among 30-39 and 40-49-year-old women. While prior studies showed that increases in overall age-adjusted incidence rates have been driven by non-endometrioid subtypes, increases in uterine cancers occurring among women <50-years-old have been driven by endometrioid subtypes (40,41). Obesity in early adulthood has been shown to be independently associated with uterine cancer risk and is more strongly associated with risk in pre- and perimenopausal women and for endometrioid subtypes (14). Lower fertility rates and older age at first birth in younger birth cohorts may also contribute to rising early onset uterine cancer rates (https://www.census.gov/library/stories/2022/04/fertility-rates-declined-for-younger-women-increased-for-older-women.html). Significant increases in localized stage disease in all three early onset age groups likely reflects the clinical characteristics of endometrioid cancers (i.e., less aggressive, commonly diagnosed at an early stage) as opposed to increased detection as there has not been substantial change to clinical practice for the diagnosis of uterine cancer, and distant stage disease also increased significantly among 30-39-year-old women. Though we did not correct rates for hysterectomy prevalence, prior work has shown that the magnitude of the trends in uterine cancer in early onset age groups is not strongly impacted by hysterectomy correction (41).
Prior studies have highlighted rapidly increasing pancreatic cancer rates among <50-year-olds in the U.S. (4), particularly among women (42,43). We did not observe concurrent increases in pancreatic cancer mortality rates in early onset age groups. However, there have been long-term increases in both pancreatic cancer incidence and mortality at older ages. In addition to obesity, rising diabetes prevalence among 20-44-year-olds as well as among older people might contribute to increases in both early onset and older onset pancreatic cancer rates (10).
The increased incidence of precursor B-cell leukemias/lymphomas, DLBCL, and MF/SS is not easily explained. Each of these subtypes has been linked with immune dysfunction, and the immune milieu continues to change in the general population, as evidenced by continued changes in prevalence of autoimmune diseases and allergy/atopic disease. However, other subtypes that are also linked to immune dysfunction did not demonstrate comparable trends in our analysis (e.g., marginal zone lymphoma, Burkitt lymphoma/leukemia, and peripheral T-cell lymphoma) (44-47). For plasma cell neoplasms, 94% of which are multiple myeloma, incidence rates increased only among women. Prior studies have reported a stronger association between obesity and progression from monoclonal gammopathy of unknown significance to multiple myeloma among women compared with men (48,49). Because of substantial changes in classification for myeloproliferative neoplasms and myelodysplastic/myeloproliferative neoplasms (MPN and MDS/MPN) as they became reportable to cancer registries (50,51), results for these entities are presented in the supplement only.
While not discussed in detail here, we also observed rising rates of melanoma, stomach cancer, testicular cancer, cervical cancer and cancers of the bones and joints. Rising rates of melanoma and stomach cancer were much stronger among women compared with men. As an estimated 93% of melanomas are caused by UV light (11), this might point to increased sun exposure and indoor tanning among women (52). Over-diagnosis of melanoma might also contribute to increasing rates (53). The rise in non-cardia stomach cancer predominantly among women may be attributed to changes in the gastric and gut microbiome, and an increase in autoimmune gastritis (54,55). Existing population-based data on Helicobacter pylori prevalence are insufficient to fully describe the magnitude of variation by age and birth cohort among U.S. population subgroups (56). Prevalence of other key risk factors for non-cardia gastric cancer, such as high salt intake (57) and smoking (58) have been stable or declining across recent birth cohorts, and thus would not explain the increasing trend. It is unclear what is causing rising rates of testicular and cervical cancers (59-62), though it is worth noting that incidence rates peak at 25-29 for testicular cancer and 40-44 for cervical cancer, and perhaps the age groups considered to be “early onset” in this paper are not appropriate for these cancer types (https://seer.cancer.gov/statistics-network/explorer/overview.html). It is also important to note that rates of cervical cancer among 15-29-year-old women are decreasing significantly, likely due to increased uptake of HPV vaccination over time (63), while those aged 30 years and older are less likely to be vaccinated.
Though not highlighted in this analysis, rates of 18 cancer types are declining in early onset age groups. For example, the largest absolute declines were observed for lung and prostate cancers. Rates of lung cancer declined nearly 40% among 40-49-year-olds over the time period, likely driven by reductions in cigarette smoking at younger ages, as the prevalence of cigarette smoking declined from 19% to 5% among 18-24-year-olds in the U.S. between 2011 and 2022 (58). Large declines in prostate cancer incidence among 40-49-year-old men were also observed, potentially driven by declines in PSA testing in this age group (https://progressreport.cancer.gov/).
While several prior studies have focused on relative increases in cancer incidence rates over time (3,4), simultaneously presenting trends in cancer mortality rates and absolute change in cancer incidence can provide broader context for the public health impact of rising early onset cancer rates. Total cancer mortality did not increase in any age group, and there were very few increases in cancer type specific mortality rates, though it is possible that we have yet to see the mortality impacts of rising incidence rates. Although the lack of mortality rate increases is somewhat reassuring, ideally cancer mortality rates would be declining. Mortality is also not the only important outcome among people diagnosed with cancer at younger ages. The lives of adolescent and young adult cancer survivors are negatively impacted by the late effects of cancer and treatment for decades after their cancer diagnoses (64).
Estimates of additional cancer diagnoses occurring in 2019 allow us to benchmark against other metrics to assess the absolute magnitude of early onset cancer increases. Additional cancers were calculated by comparing the observed number of cases in 2019 to the expected number if 2010 incidence rates had persisted. While 2010 is an arbitrary comparison, this estimate does give a sense of the size of the increase in cases in 2019 based on trends that occurred over a decade. Female breast cancer contributed the largest number of excess cancers in 2019, about 4,800 cases (driven by ER+ cancers), more than double the number of excess cancers estimated for colorectal cancer. In 2019, additional early onset cancers comprised 10% of breast cancers diagnosed in early onset ages groups, 14% of colorectal cancers, 19% of kidney cancers and 17% of uterine cancers. For context, the number of additional cancers diagnosed in early onset age groups in 2019 is on par with the number of pediatric cancers that are diagnosed annually in the U.S. (65).
The use of national data to assess early onset cancer incidence rates is a major strength of this analysis, as prior studies have used subsets of US states (3,4). In addition, the inclusion of older age groups for comparison, mortality trends and estimates of the absolute number of additional cancer diagnoses provide context for this analysis that have not been present in prior studies. It has been shown in prior analyses that both the magnitude and direction of trends in cancer rates can vary by self-reported race and ethnicity and geography within the U.S. While the goal of our analysis was to provide an overview of early onset cancer rates in the U.S., future studies should examine trends across demographics and geography in detail. As cancer registries do not collect information on cancer risk factors, screening or access to care, we were unable to provide further insight into the drivers of increasing trends in early cancer rates. More research that integrates data sets together to understand these trends is needed. In addition, future work will be needed to understand the impact of screening guideline changes for breast and colorectal cancers on incidence rates in early onset age groups, and the long-term effects of delays in cancer diagnoses in 2020 due to the COVID-19 pandemic.
In summary, while rates of certain early onset cancers have increased in the U.S. in recent years, total cancer incidence rates and mortality rates have not increased. The largest absolute increases in early onset cancers were observed for female breast, colorectal, kidney and uterine cancers. For the most common of these cancers, the increases do not appear to only be occurring among younger ages, implicating increased cancer risk across the age range. In addition, there were not concomitant increases in mortality for most cancer types with increasing incidence rates. Continued monitoring of cancer incidence and mortality rates across cancer subtypes is needed both in the U.S. and globally. In addition, more research is needed to understand the plausibility of known risk factors driving increasing and decreasing cancer rates of both early onset and older onset cancers, as well as investigations into novel risk factors that may impact cancer risk across the age range.
Methods
We utilized 2010-2019 incidence data from the United States Cancer Statistics (USCS) Database (RRID:SCR_024896), which includes population-based cancer registries from all U.S. states funded by both the Surveillance, Epidemiology and End Results program and the National Program of Cancer Registries. Data from 2020 and 2021 were not included due to artificially low cancer incidence rates in 2020 due to the COVID-19 pandemic (figures including 2020 and 2021 presented in Supplemental Figure 7)(66). Solid cancer types were defined with the SEER site recode (RRID:SCR_024687), which is based on International Classification for Diseases (ICD) Oncology version 3 codes. Hematologic cancers were classified according to the 2008 World Health Organization Classification (67). SEER summary stage was used to categorize stage at diagnosis as localized, regional, distant or unknown. For select cancer types, we further stratified our analysis by topography, histology or other tumor features, as described in supplemental table 3. For female breast cancers, estrogen receptor (ER) status was imputed when missing, based on established methods (68), and restricted to females aged 20-49, as data were too sparse among 15-19-year-olds to include in the imputation. We also examined cancer mortality rates with national death certificate data from the National Center for Health Statistics (RRID:SCR_025830) for 2010-2022 with cancer deaths classified based on ICD-10 codes.
This analysis focused on cancer types for which there were at least 100 incident cases diagnosed in 2019 in USCS among each “early-onset” age group (i.e., 15-29, 30-39 and 40-49-year-olds), or where there were at least 1,000 cases among 40-49-year-olds. The primary goal of this analysis was to identify cancer types where incidence rates increased over time among early-onset age groups during 2010-2019. The secondary goals were to 1) estimate trends in cancer incidence rates in older age groups, 2) estimate trends in cancer mortality rates across age groups, 3) estimate trends in cancer incidence rates by stage at diagnosis among early-onset age groups, and 4) estimate the absolute increase in the number of early-onset cancer cases in 2019.
Age-standardized incidence and mortality rates were estimated in 6 age groups (15-29, 30-39, 40-49, 50-59, 60-69 and 70-79 year olds), standardized to the 2000 U.S. population in 5-year-age groups using SEER*Stat software version 8.4.5 (RRID:SCR_025808). Joinpoint regression was used to estimate annual percentage changes (APCs) in rates from 2010 to 2019 and for mortality 2010 to 2022 using Joinpoint software version 5.3.0.0 (RRID:SCR_018129). Inflection points (or “joinpoints”) in the trajectory of cancer trends could occur in different calendar years for different combinations of cancer type and age group. As our focus has been to identify cancers that increased in the most recent calendar years, a cancer type was considered to be increasing significantly if the most recent APC for incidence was statistically significant and increasing. 95% confidence intervals (CIs) and p-values were calculated in Joinpoint using the Empirical Quantile Method (https://surveillance.cancer.gov/help/joinpoint/setting-parameters/method-and-parameters-tab/apc-aapc-tau-confidence-intervals/empirical-quantile). Among cancers with increasing early onset incidence rates in at least one of the three early onset age groups, we carried out additional analyses by sex, stage (when applicable), and selected tumor topography, histology and other tumor characteristics (defined in supplemental table 3). To estimate the absolute change in the number of early onset cancers due to increasing incidence rates, we compared the observed number of diagnoses in 2019 to the expected number based on 2010 rates among 15-49-year-olds. Expected number of diagnoses were estimated by multiplying age-specific 2010 rates by population estimates in 2019.
Supplementary Material
Acknowledgments
This work was funded by the Intramural Research Program of the National Cancer Institute and the Institute of Cancer Research.
Footnotes
The authors have no conflicts of interest to declare.
Data availability
U.S. Cancer Statistics data (https://www.cdc.gov/united-states-cancer-statistics/index.html) and national death certificate data (https://wonder.cdc.gov/) are publicly available from the Centers for Disease Control and Prevention.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
U.S. Cancer Statistics data (https://www.cdc.gov/united-states-cancer-statistics/index.html) and national death certificate data (https://wonder.cdc.gov/) are publicly available from the Centers for Disease Control and Prevention.