New clues emerge in early-onset colon cancer risk

Clinical takeaway: Keep early-onset colon cancer on the radar in young adults with concerning symptoms; these birth and demographic associations sharpen the etiologic picture but don't translate to screening changes.

Early-onset colon cancer is now the leading cause of cancer death before age 50 in the US, yet its drivers remain murky. Researchers have largely searched for clues at the time of diagnosis, rarely earlier in life. A new study links decades of California birth records to cancer-registry data to test whether traits present at birth track with later risk. Male sex, Hispanic ethnicity, and early-life factors all emerged as associations.

In the fully adjusted model, men had 34% higher odds of early-onset colon cancer than women, and Hispanic patients had 43% higher odds than non-Hispanic White patients. Both met the study's strict threshold for statistical significance. Having a foreign-born mother ran the other way, tied to 15% lower odds overall, an association strongest among men and absent among women.

Two further signals appeared only among women. Every 500-g increase in birthweight was linked to 10% higher odds, and having a father aged 35 or older to 56% higher odds. Neither held in men, and birthweight lost significance in the full population once other factors were accounted for. No other birth, demographic, or parental characteristic, including gestational age, birth order, delivery mode, or maternal age, was significantly associated with risk.

The California Linkage Study of Early-Onset Cancers joined state birth records with cancer-registry data spanning 1988 to 2021. Researchers compared 1,221 people diagnosed with colon cancer before age 40 against 61,050 cancer-free controls matched on birth year, then estimated odds ratios across a wide set of birth, demographic, and parental characteristics drawn from birth certificates.

What sets the study apart is its reach into factors no one had connected to early-onset disease. The protective signal from a foreign-born mother fits a pattern seen elsewhere in immigrant health: first-generation mothers tend toward healthier diets and lower obesity in pregnancy, and maternal obesity has been tied to colorectal risk in the next generation.

The paternal-age signal points a different direction, toward genetics, since older fathers pass on more de novo mutations to their children. Both remain associations without proven mechanisms, and the authors are careful to call the paternal-age finding novel and unconfirmed. Together they reframe early-onset colon cancer as a disease whose risk may be set, in part, long before adulthood.

"Our findings warrant future studies aimed to understand the mechanisms through which factors such as male sex, Hispanic ethnicity, birthweight, maternal birthplace, and paternal age may influence risk of early onset colorectal cancer," said lead author Sunny Siddique, MPH, PhD, of the Yale School of Public Health.

Source: Siddique S, et al. Cancer. 2026 Jun 22. Demographic, birth, parental characteristics, and the risk of early-onset colorectal cancer: a population-based nested case-control study in California