A large California study suggests that characteristics present at birth and parental factors may help shape the risk of developing colon cancer before age 40, offering new clues as to why rates rise in younger adults.
Study: Demographic Characteristics, Nativity, Parental Characteristics, and Risk of Early-Onset Colorectal Cancer: A Population-Based Nested Case-Control Study in California. Image credit: Tama2u/Shutterstock.com
A new study published in the journal Cancer reveals that male sex, Hispanic ethnicity, higher birth weight among women, and older paternal age are potential risk factors for early-onset colorectal cancer.
The increasing incidence of colon cancer prompts the search for early life risk factors
Colorectal cancer (CRC) is the second most common cancer and the third leading cause of cancer-related death in the United States. Although the prevalence of CRC in the elderly aged 50 years and older (late-onset CRC) has declined since the mid-1980s, diagnoses among people under the age of 50 (early-onset CRC) have steadily increased over the past two decades.
Early-onset CRC is typically found in the rectum and distal colon, and cancers in these areas are associated with excessive alcohol consumption and a high intake of a Western diet, including red meat and processed foods.
Existing studies have identified several risk factors that may increase the risk of CVD, including demographics, birth-related characteristics, and parental characteristics. However, it remains largely unknown whether these risk factors are associated with early CRC risk.
To fill this gap in the literature, researchers at the Yale School of Public Health, USA, conducted a large population-based nested case-control study to investigate the association between a range of demographic, nativity, and parental characteristics and the risk of early-onset CRC in individuals born in the state of California diagnosed before the age of 40 years.
Male gender and Hispanic nationality stand out
The study included 1221 cases of early-onset CRC diagnosed between the ages of 0 and 39 years, with a median age of diagnosis of 29 years. These cases were matched by year of birth to 61,050 cancer-free controls. The researchers found statistically significant interactions by gender, Hispanic ethnicity, and age at diagnosis, prompting further subgroup analyses.
After accounting for demographic, nativity, and parental characteristics, males had a 34% higher risk of early-onset CRC than females, while Hispanics had a 34% higher risk than non-Hispanic whites. The pooled analysis also showed that having a foreign-born mother was associated with a lower risk of early CRC.
Birth and parental factors show sex-specific patterns
In contrast, associations with birth weight and father’s age were evident only in specific subgroups. In an analysis adjusted for year of birth only, each 500-gram increase in birth weight was associated with a 6% increase in the risk of early-onset CRC, but this association was no longer statistically significant after adjustment for all demographic, nativity, and parental characteristics. However, when the data were analyzed separately by sex, each 500-gram increase in birth weight was associated with a 10% higher risk in women, while no significant association was seen among men.
A similar pattern was observed for paternal age. Women whose fathers were aged 35 years or older had a significantly higher risk of early-onset CRC, while no significant association was found among men. The protective association with mother’s place of birth also differed by gender: having a foreign-born mother was associated with lower risk among men, but no statistically significant association was observed among women.
The study identifies several early life risk factors
Analyzing a large set of demographic, nativity, and parental characteristics, the study reveals that male sex, Hispanic ethnicity, higher birth weight among women, and older paternal age among women were associated with a higher risk of early-onset CRC only in specific subgroup analyses, while having a foreign-born mother was associated with a lower risk, particularly among men.
Evidence has linked higher levels of free testosterone in the blood to an increased risk of CRC, which may explain why men have a higher risk of developing early-onset CRC than women. Furthermore, clinical evidence has pointed to an inverse association between estrogen and CRC risk, reflecting a protective effect of female reproductive hormones.
Why might these factors affect cancer risk?
Recent evidence suggests that Hispanic individuals are more likely to develop CRC at an earlier age. The findings of the current study also support this evidence by showing that Hispanic women and men had 39% and 45% higher risks, respectively, of early-onset CRC compared with their non-Hispanic white counterparts. A number of structural barriers may explain this disparity, including limited access to cancer screening and care, language and cultural competence, lower income, and lack of health insurance.
A notable finding of this study is that offspring of foreign-born mothers were associated with a lower risk of early-onset CRC, particularly among male children. Although the mechanism leading to this protective effect remains largely unknown, a healthier dietary pattern and a lower prevalence of obesity during pregnancy in first-generation foreign-born Hispanic women compared with their US-born counterparts may partially explain the observed benefit in offspring.
The study reports that women who have a father aged 35 or older are significantly more likely to develop early-onset CRC. A possible explanation for this finding may be its increased rate de novo mutations among children born to older fathers. In this context, a genome-wide mutation study reported that the variation in mutation rates of single nucleotide polymorphisms strongly depends on the age of the father at the time of child conception.
The study has important limitations
The authors also noted several limitations. The study only included people diagnosed before the age of 39, so the findings may not generalize to all early-onset CRC cases diagnosed between the ages of 40 and 49.
The subgroup analysis of subjects aged 0–19 included relatively few cases, parental education data were missing for approximately 70% of participants, and unmeasured factors such as maternal obesity may have influenced the results. Because multiple factors were examined, some associations may also reflect false positive findings due to multiple comparisons.
Early life factors may help explain the rise in CRC
Overall, this large, population-based, nested case-control study identifies a set of novel demographic, birth, and parental factors that may contribute to the risk of early-onset CRC. Future studies are needed to further validate and evaluate potential mechanisms.
