MALE sex and Hispanic ethnicity increase early-onset colorectal cancer risk, while foreign maternal birthplace provides protection. In a large population-based nested case-control study from the California Linkage Study of Early-Onset Cancers, investigators evaluated statewide birth records matched with cancer registry data from 1988 through 2021. The investigation encompassed 1,221 individuals diagnosed with first primary early-onset colorectal cancer between ages 0 and 39 years, along with 61,050 birth-year matched control subjects without cancer diagnoses. Researchers performed multivariable logistic regression to elucidate how demographic, birth, and parental characteristics influence early malignancy.
Identifying Early-Onset Colorectal Cancer Risk Factors Across Diverse Populations
Fully adjusted statistical models revealed distinct demographic disparities in cancer risk. Males demonstrated a 34 percent increased risk of developing early-onset colorectal cancer compared with females. Additionally, Hispanic ethnicity was associated with a 43 percent higher risk compared to non-Hispanic White individuals. Stratified analyses showed elevated risk among Hispanic males and females alike. Conversely, offspring born to foreign-born mothers exhibited a 15 percent lower overall risk of developing early-onset disease, an effect particularly pronounced among male offspring who experienced a 21 percent risk reduction.
Examining Perinatal and Parental Exposures
Sex-stratified evaluations demonstrated that specific biological and developmental variables selectively alter early-onset colorectal cancer risk factors. Among female offspring, each 500-gram increase in birthweight was associated with a 10 percent increase in cancer risk. Furthermore, females born to fathers aged 35 years or older faced a 56 percent elevated risk of developing colorectal cancer compared to those with younger fathers. Among young adults aged 20 to 39 years, higher birthweight also correlated with a 5 percent risk increase per 500-gram increment.
No statistically significant associations were identified for gestational age, birth order, delivery mode, birth plurality, maternal age, maternal education, or maternal pregnancy complications. Clinical management of early-onset disease requires ongoing investigation into early environmental exposures, maternal metabolic health, and paternal age mechanisms. Understanding how these early-life influences shape early-onset colorectal cancer risk factors will assist clinicians in recognizing subtle predispositions and informing future screening considerations.
Reference
Siddique S et al. Demographic, birth, parental characteristics, and the risk of early-onset colorectal cancer: A population-based nested case-control study in California. Cancer. 2026;e70458. doi:10.1002/cncr.70458
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