Key takeaways:

• Parental factors, such as where mothers were born, could significantly affect risk for early-onset colorectal cancer.
• Sex-based differences highlight need for future research, particularly the gut microbiome.

Early life factors such as where an individuals’ parents are born and the age at which they had children may significantly affect risk for early-onset colorectal cancer in offspring.

An investigation of more than 1,200 people from California showed men and Hispanic individuals had significantly increased risk for early-onset colorectal cancer.

Data derived from Siddique S, et al. Cancer. 2026;doi:10.1002/cncr.70458.

Additionally, researchers found those whose mothers were born outside the U.S. had a 15% lower likelihood of developing the malignancy before the age of 40 years, and women with fathers aged 35 years and older had 56% greater odds.

“Birth characteristics are often neglected when we try to understand what causes cancer,” Sunny Siddique, MPH, PhD, postdoctoral fellow and cancer epidemiologist at Yale School of Public Health, told Healio.

“Early life exposures provide critical information about who would eventually develop cancer and who should also be screened.”

‘The big buzz’

Overall, colorectal cancer incidence declined 0.9% annually from 2013 to 2022, Healio previously reported.

However, that decrease can be attributed to individuals aged 65 years and older (2.5% decline). Incidence increased 0.4% per year for those aged 50 to 64 years, and 3% for those aged 20 to 49.

Of the top five leading causes of cancer-related death among individuals aged 50 years and younger, only colorectal cancer mortality increased from 1990 to 2023, elevating it from the No. 5 killer between 1990 and 1994 to No. 1 in 2023, according to data published in JAMA earlier this year.

“It’s the big buzz in the colorectal world,” Siddique said.

Body weight, diabetes, diet, and smoking and alcohol use are all risk factors for colorectal cancer, according to American Cancer Society.

Those may be less applicable in younger cohorts, though.

“Somebody who is older may be more affected by lifestyle factors that accumulate over the lifespan,” Siddique said. “With early-onset cancers, it’s much more relevant to look at early life factors, for example, whether your mom had any pregnancy-related complications at birth, and how does that affect long-term outcomes in the offspring. We were really interested in understanding that early-life picture.”

Siddique and colleagues used the California Linkage Study of Early‐Onset Cancers to investigate whether child, maternal and paternal characteristics had any associations with early-onset colorectal cancer incidence.

They included 1,221 cases (mean age at diagnosis, 29.07 years; standard deviation, 5.8; 58.8% men; 44.88% Hispanic; 36.45% white) diagnosed between 1988 and 2021, and matched that group to 61,050 controls based on patients’ birth year.

Demographic, birth and parental factors associated with early-onset colorectal cancer served as the primary endpoint.

‘Surprising’

Men had a significantly higher likelihood of developing early-onset colorectal cancer than women (OR = 1.35; 95% CI, 1.21-1.52).

Hispanic individuals also had significantly greater odds compared with white individuals (OR = 1.34; 95% CI, 1.2-1.51).

Individuals with a foreign-born mother had significantly lower odds of developing early-onset colorectal cancer (OR = 0.85; 95% CI, 0.73-0.97), specifically men (OR = 0.79; 95% CI, 0.65-0.95).

“It was surprising to see the protective side of your mother being born in a foreign country,” Siddique said. “Perhaps differences in exposures among foreign-born individuals, such as diet, may contribute to these differences.”

Women had a significantly higher risk for disease if they had fathers aged 35 years and older (OR = 1.56; 95% CI, 1.08-2.25).

A 500 g increase in birthweight trended toward an increased risk for early-onset colorectal cancer overall, but it did not reach statistical significance.

It did, however, among women (OR = 1.1; 95% CI, 1.01-1.21).

“Why would that be?” Siddique asked. “There are new studies that are coming out showing that the gut microbiome among men and women are different. Risk factors by sex vary.”

Researchers acknowledged study limitations, including the cohort only including patients aged 39 years and younger.

Siddique noted future research could include analyses of other U.S. states, not just California.

He also highlighted two critical areas of research to pay attention to — the gut microbiome and the impact of increasing use of medications, such as GLP-1s, that modify colorectal cancer risk factors.

For more information:

Sunny Siddique, PhD, MPH, can be reached at sunny.siddique@yale.edu.