Early-Onset Cancers Are on the Rise: Why It’s Happening and What We Can Do

A growing body of research suggests that rates of early-onset cancers — those affecting patients younger than 50 years of age — have been rising since the 1990s.^1-6

Studies have shown increasing rates of early-onset breast, lung, gastrointestinal, gynecologic, genitourinary, and hematologic cancers, among others.

“Overall trends show many of the cancers with the largest increases in early-onset disease are in the gastrointestinal tract, including cholangiocarcinoma, colorectal, gastric, appendix, and pancreatic cancers,” said Suneel D. Kamath, MD, of the Cleveland Clinic Taussig Cancer Institute in Ohio.

The increasing incidence of early-onset cancers is expected to continue for the near future, said William M. Grady, MD, of Fred Hutchinson Cancer Center in Seattle, Washington.

However, researchers have suggested that lifestyle changes and reducing exposures to environmental carcinogens could help lower rates of early-onset cancers. Implementing cancer screening at younger ages and modifying treatment approaches could improve outcomes for patients who do develop early-onset cancers.

Trends in Early-Onset Cancers

In a study published in JAMA Network Open last year, researchers examined patterns in the incidence of early-onset cancers in the US from 2010 through 2019, based on data from the SEER 17 database.¹ The authors identified 562,145 patients with early-onset cancer during the study period.

The results revealed an increase in the incidence of early-onset cancers — from 99.96 cases per 100,000 people in 2010 to 102.97 cases per 100,000 in 2019, for an annual percentage change (APC) of 0.28% (P =.01). At the same time, there was a reduction in the incidence of cancer for individuals aged 50 years and older (APC, -0.87%; P <.001).

The researchers also found that incidence rates of early-onset cancer increased in women (APC, 0.67%; P =.001) but decreased in men (APC, -0.37%; P <.001).

The greatest increase in early-onset cancers over the study period was seen for gastrointestinal cancers (APC, 2.16%; P <.001). In 2019, most early-onset cancers were breast cancer (n=12,649), followed by thyroid cancer (n=5869), and colorectal cancer (n=4097).

In another study, published in BMJ Oncology last year, researchers found a 79.1% increase in the global incidence of early-onset cancer and a 27.7% increase in the number of related deaths between 1990 and 2019.²

Nasopharyngeal cancer (estimated APC, 2.28%) and prostate cancer (estimated APC, 2.23%) were the fastest-growing early-onset cancers. However, breast cancer had the highest incidence rate (13.7 per 100,000) and mortality rate (3.5 per 100,000) among early-onset cancers.

The highest mortality rates and disability-adjusted life years were observed for early-onset breast, tracheal, bronchus and lung, stomach, and colorectal cancers.

Data from the American Cancer Society revealed that colorectal cancer cases among individuals younger than 55 years increased from 11% in 1995 to 20% in 2019.³

Other research has shown increasing rates of early-onset endometrial cancer, with a disproportionate burden of cases observed in patients who are Hispanic, non-Hispanic Black, and non-Hispanic Asian/Pacific Islander.⁴

Proposed Risk Factors for Early-Onset Cancers

Research has suggested that genetics play a role in the risk of early-onset cancers. In a study published in 2021, researchers found a higher risk of early-onset cancers for first-degree relatives of patients with early-onset cancer (standardized incidence ratio [SIR], 3.32; 95% CI, 2.85–3.85).⁵ The research also revealed an increased risk of second primary malignancies in patients with early-onset cancers (SIR, 7.27; 95% CI, 6.56-8.03).

Research has also suggested several other factors may be driving the increase in early-onset cancers, Dr Grady noted. He said these factors include “increasing rates of obesity, decreasing physical activity, increasing incidence and younger age of onset of adult-onset diabetes mellitus, increased exposure to chemicals in plastics and microplastics, poor sleep hygiene, and dietary changes such as increased consumption of ultra-processed foods and refined sugars and decreased consumption of whole foods.”^6,7

In the BMJ Oncology study, for example, researchers identified dietary factors — such as a diet high in red meat and sodium and low in fruit, whole grains, and calcium — as well as alcohol and tobacco use as the main risk factors for early-onset cancer.²

Dr Kamath noted that some data have linked long-term or recurrent antibiotic use in early life to an increased risk of early-onset colorectal cancer via alterations in the gut microbiome.⁸

The increasing rates of early-onset colorectal cancer “are not due to an increase in germline-syndrome related cancers, as 70% of these cancers are sporadic in younger patients, so there is clearly some environmental exposure(s) that may be a driver,” Dr Kamath noted.⁹ 

Screening and Prevention

The rising rates of early-onset cancer highlight the need to increase awareness among young people and primary care providers and to initiate cancer screenings at younger ages, according to Dr Grady.

“The challenge is that earlier screening will not be covered by insurance until the change in incidence is confirmed through further research and is then recommended by authorities such as society organizations including ASCO and AGA,” Dr Grady said.

In the meantime, clinicians should make sure patients are screened as early as possible, Dr Kamath advised.

“For colorectal cancer, the screening age is now 45 in order to capture more early-onset disease, as the majority of early-onset colorectal cancer occurs in people ages 45-49,” he said.¹⁰ “For breast cancer, there are many conflicting guidelines, but Cleveland Clinic recommends beginning screening at age 40 or earlier with family history.”¹¹

Dr Kamath also emphasized the need for providers to conduct a thorough family history.

“Many patients that are diagnosed with cancer talk with their families after their diagnosis and find out that many family members had cancer that they didn’t know about,” he said. “Encourage patients to have these conversations because more people than we think are high risk and should be screened sooner.”

Dr Grady also noted the importance of encouraging patients to embrace a “healthy lifestyle and diet in their teens and 20s when they can adopt patterns of daily living that will last their lifetimes.”

Treatment Considerations for Early-Onset Cancers

Patients diagnosed with early-onset cancer may have different treatment needs than patients with late-onset cancer due to differing phase-of-life circumstances.^12,13

“These patients face unique challenges, as they are often experiencing serious illness for the first time and at a critical time in their lives when people are typically starting families and careers,” Dr Kamath said. “They need more social support for transportation, childcare, and replacing lost income, and they also need mental health support because going through cancer at age 30 is very different than at age 70.”

Additionally, fertility is a major concern for many patients with early-onset cancer, and those who are interested should be referred for fertility preservation in a timely manner to avoid delays in cancer treatment, Dr Kamath said.¹⁴

“We also need to ensure that every person with early-onset cancer is referred for genetic counseling and gets germline genetic testing,” he added.¹⁵

While there are currently no professional guidelines regarding the treatment of early-onset cancers in general, Dr Grady highlighted several considerations for clinicians caring for younger patients with cancer.

He noted that the impact of long-term therapy-related complications on quality of life is more of an issue in young people than in older people. For example, oxaliplatin causes peripheral neuropathy in many people, resulting in loss of sensation in the fingers, toes, and, in more severe cases, the entire hands and feet. This can be disabling for people who have physical jobs that require dexterity.

The risks of chemotherapy-induced cancers — typically lymphomas — are more of an issue in younger people because of their longer life expectancy, Dr Grady said. In that same vein, the need to adopt a healthy lifestyle and diet to reduce the risk of future cancers is more important in patients with early-onset cancer because of their longer life expectancy.

Future Directions

“By far, the greatest need is more research to identify the environmental factors that are driving the increasing incidence of early-onset cancer,” Dr Kamath said. “There is a lot of speculation, and there are some known triggers, but these don’t explain the full story, and a lot more work is needed.”

Among numerous other research priorities regarding early-onset cancers, Dr Grady highlighted the need to “determine more effective ways to get people to consistently adopt healthy behavior lifestyles” and examine whether such lifestyle changes could reverse the current trends, as well as to “promote research on the cellular and molecular mechanisms that drive cancer initiation and progression.”

Both physicians cited the need for novel screening approaches to detect a greater number of cancer cases.

“With the current screening modalities, it is not practical to start screening everyone by age 20, but if we had a cost-effective approach with appropriate positive and negative predictive value, this could be implemented in the whole population at a much younger age to catch these early-onset cancer diagnoses sooner,” Dr Kamath said.

Disclosures: Dr Grady disclosed relationships with Guardant Health, SEngine Precision Medicine, DiaCarta Inc., and Natera. Dr Kamath said he has no relevant disclosures.

This article originally appeared on Cancer Therapy Advisor